Methods and compositions for treating sexual disorder, weight loss, weight maintenance, well-being, and self-esteem

Abstract

The invention further relates to compounds, pharmaceutical compositions and methods for treating a subject for sexual function, such as sexual disorder or sexual dysfunction (SD), for inducing subject weight loss, for effectuating weight maintenance by a subject, whether or not the weight maintenance is used alone or in combination with a subject's weight loss, and / or for improving a subject's subjective state of well-being, self-esteem and / or self-confidence. Examples of SD contemplated by the present invention include but are not limited to female sexual disorder (FSD), female sexual arousal disorder (FSAD), female sexual interest / arousal disorder (FSIAD), female hypoactive sexual desire disorder (HSDD), female orgasmic disorder (FOD), female sexual pain disorder (FSPD), sexual interest arousal disorder (SIAD), male sexual disorder (MSD), male hypoactive sexual desire disorder (MSHDD), erectile dysfunction (ED), Pyronine's disease (PD), male premature ejaculation (MPE), male delayed ejaculation (MDE), male decreased libido (MDL), male dry orgasm (MDO).

Description

Attorney Docket No.49848-4040PCT METHODS AND COMPOSITIONS FOR TREATING SEXUAL DISORDER, WEIGHT LOSS, WEIGHT MAINTENANCE, WELL-BEING, AND SELF-ESTEEM RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 650,164, filed May 21, 2024, and to U.S. Provisional Patent Application No.63 / 650,042, filed May 21, 2024, of which the contents of both are incorporated herein by reference in their entireties as if fully set forth herein.

[0002] PCT / US2012 / 031991, PCT / US2016 / 038386, U.S. Utility Patent Application No. 14 / 045677, U.S. Provisional Patent Application No. 61 / 471,505, and U.S. Provisional Patent Application No. 61 / 471,505 and their contents are incorporated herein by reference in their entireties as if fully set forth herein. FIELD OF THE INVENTION

[0003] The invention further relates to compounds, pharmaceutical compositions and methods for treating a subject for sexual function, such as sexual disorder or sexual dysfunction (SD), for inducing subject weight loss, for effectuating weight maintenance by a subject whether or not the weight maintenance is used alone or in combination with a subject’s weight loss, and / or for improving a subject’s subjective state of well-being, self- esteem and / or self-confidence. BACKGROUND OF THE INVENTION

[0001] Sexual disorder or sexual dysfunction (“SD”) can be any problems that prevent a person or couple from experiencing satisfaction from sexual activity. Some 43% of women and 31% of men report some degree of sexual dysfunction. See, for example, Sexual Dysfunction, Cleveland Clinic available online at https: / / my.clevelandclinic.org / health / diseases / 9121-sexual-dysfunction.

[0002] Broadly speaking, SD includes female sexual dysfunction (“FSD”) and male sexual dysfunction (MSD”).Attorney Docket No.49848-4040PCT

[0003] Female Sexual Dysfunction (FSD) is described as an interruption in sexual functioning. FSD includes numerous subtypes, namely, hypoactive sexual desire disorder (“HSDD”), female sexual arousal disorder (“FSAD”), female orgasmic disorder (“FOD”) and female sexual pain disorder (FPD”). See, for example, Erdős C, Kelemen O, Pócs D, Horváth E, Dudás N, Papp A, Paulik E. Female Sexual Dysfunction in Association with Sexual History, Sexual Abuse and Satisfaction: A Cross-Sectional Study in Hungary. J Clin Med.2023 Jan 31;12(3):1112. doi: 10.3390 / jcm12031112. PMID: 36769759; PMCID: PMC9918233. FSD also includes female sexual interest / arousal disorder (“FSIAD”).

[0004] The symptoms can vary for each type of FSD. HSDD or low sexual disorder is thought to be the most common type of FSD and involves a lack of sexual interest and willingness to be sexual. HSDD is defined by the DSM-IV-TR (defined herein after) as: “The persistent lack (or absence) of sexual fantasies or desire for any form of sexual activity marked by distress or interpersonal difficulty and not better accounted for by another disorder (except another sexual dysfunction) direct physiological effects of a substance (including medications) or a general medical condition.” The presence of distress or interpersonal difficulty is an integral part of HSDD and is central to the diagnosis of the condition. Approximately 1 in 10 women reported low sexual desire with associated distress, which may be HSDD. FSAD or sexual arousal disorder involves women whose desire for sex might be intact, but they have difficulty with arousal or are unable to become aroused or maintain arousal during sexual activity. FOD or orgasmic disorder. You have persistent or recurrent difficulty in achieving orgasm after sufficient sexual arousal and ongoing stimulation. FSPD or female sexual pain disorder involves women who have pain associated with sexual stimulation or vaginal contact. See, for example, Female dysfunction, Diseases and Conditions, Mayo Clinic, available online at https: / / www.mayoclinic.org / diseases-conditions / female-sexual-dysfunction / symptoms-Attorney Docket No.49848-4040PCT

[0005] HSDD as discussed above concerns "a deficiency or absence of sexual fantasies and desire for sexual activity. The disturbance must cause marked distress or interpersonal difficulty." See Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-IV-TR), 4th Ed., Text Rev. Washington, DC: American Psychiatric Association, 2000; and International Classification of Diseases (ICD-10, F52.0). More specifically, HSDD is defined as an absence or marked reduction in desire or motivation to engage in sexual activity as manifested by any of the following: 1) reduced or absent spontaneous desire (sexual thoughts or fantasies); 2) reduced or absent responsive desire to erotic cues and stimulation; or 3) inability to sustain desire or interest during sexual activity. The pattern is persistent or recurrent over a period of at least several months and occurs frequently, though may fluctuate in severity, and is not secondary to a sexual pain disorder. See Clayton AH, Kingsberg SA, Goldstein I; Evaluation and management of hypoactive sexual desire disorder. Sex Med. 2018;6(2):59-74; and Pachano Pesantez GS, Clayton AH; Treatment of hypoactive sexual desire disorder among women: general considerations and pharmacological options. Focus (Am Psychiatr Publ).2021;19(1):39-45.

[0006] HSDD is one of, if not, the most common sexual dysfunction problems presented today to clinicians for diagnosis and treatment. HSDD affects men and women of all ages. According to myVMC, it is estimated that approximately 20% of men and 33% of women are affected by low or absent sexual desire. See "Hypoactive Sexual Desire Disorder (HSDD)", reported at http: / / wv,'w.mvvmc.com / diseases / hypmtctive--sexual--desire-- disorder-hsdd / .

[0007] HSDD affects more than 12 million women and 8 million men in the US alone, yet it is widely misunderstood and often misdiagnosed and undertreated. It is characterized by low sexual desire that causes significant personal distress or interpersonal difficulty. It is important to note that HSDD is not a physical disorder, such as erectile dysfunction (ED) or pain during intercourse. To date, Addyi® (flibanserin) is the only FDA-approved medication for the treatment of HSDD women in the United States. Addyi (flibanserin) is a serotonin 1A receptor agonist and a serotonin 2A receptor antagonist. See, for example,Attorney Docket No.49848-4040PCT Clayton AH, Kingsberg SA, Goldstein I; Evaluation and management of hypoactive sexual desire disorder. Sex Med.2018;6(2):59-74. Unfortunately, according to the FDA, Addyi® (flibanserin), on average, only about 10% more patients treated with Addyi® than placebo reported clinically meaningful improvement, i.e., about one satisfying sexual event per month compared to a placebo. Addyi® (flibanserin) is not without risk, however. About 1 in 6 women who take Addyi® (flibanserin) experience clinically significant hypotension and syncope, which side effects are exacerbated by alcohol consumption. See, for example, Holt H, et al.; Flibanserin (Addyi) for Hypoactive Sexual Desire Disorder in Premenopausal Women. Am Fam Physician.2016;93(10):826-828; and Simon JA, et al.; Clinically meaningful benefit in women with hypoactive sexual desire disorder treated with flibanserin. Sex Med.2022;10(1):100476.

[0008] HSDD can have serious deleterious effects on the overall health of women, their quality of life, and the well-being of their personal relationships. The lack of sexual desire in women may not only cause severe psychological, emotional and / or relationship distress which, in some cases, can be severe and debilitating, it can negatively impact their personal relationships, quality of life, and well-being. HSDD can be a major impediment to life satisfaction and happiness.

[0009] A majority of HSDD cases are generalized in subtype, though a substantial minority of cases may relate to dissatisfaction or loss of interest in the sexual partner. Either subtype of HSDD can lead to general feelings of dissatisfaction in the person and / or discord in their personal relationships, including for example marital discord. HSDD, whether generalized or situational, often does not respond to counseling therapy, and frequently culminates in separation, finding a new sexual partner, and divorce. As there is no currently approved treatment for HSDD in the United States, a therapeutic composition and methods for ameliorating HSDD is an unmet need for a significant portion of the population and their quality of life. Delineated herein are compositions and methods of treatment that may be useful to address this unmet need based on heretofore unexpected properties possessed by the subject compositions.Attorney Docket No.49848-4040PCT

[0010] FSAD another a subtype of female sexual dysfunction that is characterized by physiological findings or damage to the gynecological system. FSAD generally involves women are distressed due to their inability to attain or maintain adequate vaginal lubrication. Low or lack of vaginal estrogen, arterial insufficiency, tactile insensitivity and / or relationship conflicts are common causes of FSAD. Typical treatments include hormone therapies, e.g., testosterone or estrogen patches, pills, and topical creams, and anxiety or depression therapy that may have sexual side effects. Specifically, estrogen is believed to improve vaginal tone and elasticity, increase vaginal blood flow, and enhance lubrication. See, for example, Feldhaus-Dahir M. The physiology and causes of female sexual arousal disorder: part I. Ural Nurs. 2009 Nov-Dec;29(6):440-3. PMID: 20088237.

[0011] FOD involves orgasm that is absent, infrequent, markedly diminished in intensity, or markedly delayed in response to stimulation despite normal levels of subjective arousal. Conn , Hodges, KR. Female Orgasmic Disorder. Merck Manual Professional Version. Jul 2023, available online at https: / / www.merckmanuals.com / professional / gynecology-and-obstetrics / female-sexual-Text Revision, as a persistent or recurrent delay in, or absence of, orgasm following a 'normal' sexual excitement phase. FOD is a common problem affecting sexual function in a substantial proportion of women. Studies suggest that it is prevalent in 11-41% of women worldwide and can have a tremendous impact on the individual's quality of life, relational satisfaction and general well-being. See, for example, Rellini AH, Clifton J. Female orgasmic disorder. Adv Psychosom Med. 2011;31:35-56. doi: 10.1159 / 000328807. Epub 2011 Oct 10. PMID: 22005203.

[0012] FSPD is believed to affect about 15% of women. FSPD involves women who experience chronic and / or intermittent pain in and / or around the vulva, vagina, or uterus. Symptoms commonly associated with FSPD may include chronic pelvic pain, vaginismus (tightening of the vaginal muscles upon penetration), dyspareunia (pain during sex), andAttorney Docket No.49848-4040PCT vulvodynia (pain in the vulva). Women differentiate menstrual cramp pain from FSPD pain and often described FSP pain as sharp pain in and / or around the vulva, inside the vagina, or a cramping in the muscles in the area. FSPD can negatively impact women in daily functioning, sexual satisfaction, and relationships. Current treatments for FSPD include cognitive behavioral therapy that may be used in combination with medication and hormone therapy. See, for example, FEMALE SEXUAL PAIN, ABCT Fact Sheets. Association for Behavioral and Cognitive Therapies, available online at https: / / www.abct.org / wp-content / uploads / 2021 / 03 / female-sex-pain.pdf.a concerns women. FSIAD symptoms include a lack of or significantly reduced sexual interest / arousal which can lead to distress and / or interpersonal difficulties. See, for example, Adebisi OY, Carlson K. Female Sexual Interest and Arousal Disorder. [Updated 2024 Oct 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https: / / www.ncbi.nlm.nih.gov / sites / books / NBK603746 / .

[0014] a or group male sexual functioning. Common MSDs include male hypoactive sexual desire disorder (MHSDD), erectile dysfunction (ED), Peyronie’s disease (PD), male premature ejaculation (MPE), male delayed ejaculation (MDE), male decreased libido (MDL), sexually transmitted infections (STIs), and male dry orgasm (MDO), defined by impaired sexual functioning.

[0015] MHSDD is defined in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, 2013 (DSM-5), as persistent or recurrently deficient sexual or erotic thoughts, fantasies, and desire for sexual activity. Other common symptoms of MHSDD include little to no sex drive, reduced interest in sex and sexual activities, unaroused by visual or sexual stimulation, inability to experience spontaneous desire, decreased interest in self- pleasure, i.e., masturbation, and loss of erectile / ejaculatory function. These symptoms must have persisted for a minimum of six months, and they must cause clinically significant distress. The disorder is specified by severity level and subtyped into lifelong versus acquired, generalized versus situational. See, for example, Meston CM and Stanton AM. Hypoactive Sexual Desire Disorder. The Sexual PsychophysiologyAttorney Docket No.49848-4040PCT Laboratory, Department of Physiology, The University of Texas at Austin, available online at https: / / labs.la.utexas.edu / mestonlab / hypoactive-sexual-desire-disorder / ; and White- Gibson Z. All About Male Hypoactive Sexual Desire Disorder (MHSDD). PsychCentral.sexual-desire-disorder-symptoms. In 2022, a revised version (DSM-5-TR) wasSee American . ofText Revision (DSM-5-TR). Washington, DC, USA: American Psychiatric Publishing. ISBN 978-0-89042-575-6.

[0016] MSD prevalence increases with age and is higher in more than 50% of men who are between the ages of 40 and 70, who typically describe some degree of erectile dysfunction. See, for example, Anderson D, Laforge J, Ross MM, Vanlangendonck R, Hasoon J, Viswanath O, Kaye AD, Urits I. Male Sexual Dysfunction. Health Psychol Res. 2022 Aug 20;10(3):37533. doi: 10.52965 / 001c.37533. PMID: 35999971; PMCID: PMC9392840, and Male sexual problems. Health Direct, available online at https: / / www.healthdirect.gov.au / male-sexual-problems.an aminoketone group, structurally related to cathinone, an amphetamine-like stimulant. Bupropion is metabolized in the liver and its major active metabolites, hydroxybupropion, threohydrobupropion, and erythrohydrobupropion, have higher plasma concentrations than bupropion. While the mechanism of action of bupropion is not completely understood, bupropion and its major metabolites are believed to exert their effects by inhibiting dopamine and norepinephrine reuptake and by blocking several nicotinic receptors in the brain. See, for example, Costa R, Oliveira NG, Dinis-Oliveira RJ; Pharmacokinetic and pharmacodynamic of bupropion: integrative overview of relevant clinical and forensic aspects. Drug Metab Rev. 2019;51(3):293-313. In other words, bupropion primarily acts through the norepinephrine transporter (“NET”) and the dopamine transporter (“DAT”) with additional cytochrome P450 2D6 (CYP450 2D6) inhibition. See, for example, Stahl SM. Dextromethorphan / Bupropion: A Novel Oral NMDA (N-methyl-d-aspartate) Receptor Antagonist with Multimodal Activity. CNS Spectrums. 2019;24(5):461-466. doi:10.1017 / S1092852919001470.Attorney Docket No.49848-4040PCT

[0018] Bupropion is the only synthetic cathinone approved by the FDA. Bupropion is related to phenylethylamines and is similar in structure to cathinone, an amphetamine- like stimulant, as indicated above, and diethylpropion, an appetite suppressant and sympathomimetic agent. In addition to inhibiting norepinephrine and dopamine reuptake to boost the levels of dopamine and norepinephrine in the brain, it is also thought that bupropion and / or its active metabolites may stimulate norepinephrine release through vesicular monoamine transporter-2 (VMAT-2) activation, which is similar to how amphetamines and cathinones work. See Murray B, et al.; Toxicology investigators consortium (toxic). Single-agent bupropion exposures: clinical characteristics and an atypical cause of serotonin toxicity. J Med Toxicol.2020 Jan;(1):12-16; and Baumann MH; Neuropharmacology of synthetic cathinones. Handb Exp Pharmacol.2018;252:113-142. Bupropion is also believed to have similar mechanisms of action to diethylpropion in the CNS to boost norepinephrine and dopamine levels. These chemicals are believed to act on the brain's appetite center in the hypothalamus to reduce appetite. Bupropion is an antidepressant and smoking cessation agent, while diethylpropion is an appetite suppressant used to treat obesity in the short-term management of obesity, along with dietary and lifestyle changes. See Arias HR, Santamaría A, Ali SF; Pharmacological and neurotoxicological actions mediated by bupropion and diethylpropion. Int Rev Neurobiol. 2009;88:223-55.

[0019] Trazodone inhibits serotonin transporter, serotonin type 2 receptors and the reuptake of serotonin. Trazodone also blocks histamine and alpha-1-adrenergic receptors and induces significant changes in 5-HT presynaptic receptor adrenoreceptors. Trazodone lowers levels of neurotransmitters associated with arousal effects, such as serotonin, noradrenaline, dopamine, acetylcholine, and histamine. Lower doses of trazodone are believed to induce sedation by antagonizing the 5-HT2A receptors, H1 receptors, and alpha-1-adrenergic receptors. Nevertheless, the full spectrum of trazodone’s mechanism of action is not fully understood. See, for example, Shin JJ, Saadabadi A. Trazodone. [Updated 2022 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-, available online atAttorney Docket No.49848-4040PCT https: / / www.ncbi.nlm.nih.gov / books / NBK470560 / . See also Cuomo A., Bianchetti A, Cagnin A. et al: Trazodone: a multifunctional antidepressant. Evaluation of its properties10.36150 / 2499-6564-N320; and the Desyrel® (trazodone) FDA approved label, June 2017, available online at https: / / www.accessdata.fda.gov / drugsatfda_docs / label / 2017 / 018207s032lbl.pdf.to produce meta-chlorophenylpiperazine (m-CPP), an active metabolite that possesses serotonergic activity. Trazodone and m-CPP are substrates for CYP2D6, trazodone is metabolized to a lesser extent by CYP3A4, and trazodone undergoes oxidation. See, for example, Buysse DJ, Tyagi,S. Clinical Pharmacology of Other Drugs Used as Hypnotics. Principles and Practice of Sleep Medicine. Eds: Meir Kryger, Thomas Roth and William C. Dement (Sixth Edition), 2017, Elsevier Inc. https: / / doi.org / 10.1016 / C2012-0-03543-0; Rotzinger S, Jian Fang J, and Glen B. Baker Trazodone Is Metabolized tom-Chlorophenylpiperazine by CYP3A4 from Human Sources. Drug Metabolism and Disposition. June 1, 1998, 26(6) 572-575. Thomas JM, Dourish CT, Tomlinson JW, Hassan-Smith Z, Higgs S. Effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine on appetite, food intake and emotional processing in healthy volunteers. Psychopharmacology (Berl). 2014 Jun;231(12):2449-59. doi: 10.1007 / s00213-013-3409-x. Epub 2014 Jan 10. PMID: 24408211. See also Abramowski D., Rigo M., Duc D., Hoyer D., Staufenbiel M. Localization of the 5-hydroxytryptamine2C receptor protein in human and rat brain using specific antisera. Neuropharmacology. 1995;34:1635–1645; Barnes N.M., Sharp T. A review of central 5-HT receptors and their function. Neuropharmacology.1999;38:1083– 1152; Maura G, Marcoli M, Pepicelli O, Rosu C, Viola C, Raiteri M. Serotonin inhibition of the NMDA receptor / nitric oxide / cyclic GMP pathway in human neocortex slices: involvement of 5-HT(2C) and 5-HT(1A) receptors. Br J Pharmacol. 2000 Aug;130(8):1853-8. doi: 10.1038 / sj.bjp.0703510. PMID: 10952674; PMCID: PMC1572268; Pompeiano M., Palacios J.M., Mengod G. Distribution of the serotonin 5- HT2 receptor family mRNAs: comparison between 5-HT2A and 5-HT2C receptors. Mol. Brain Res.1994;23:163–178; Abramowski D., Rigo M., Duc D., Hoyer D., Staufenbiel M. Localization of the 5-hydroxytryptamine2C receptor protein in human and rat brain usingAttorney Docket No.49848-4040PCT specific antisera. Neuropharmacology. 1995;34:1635–1645; Barnes N.M., Sharp T. A review of central 5-HT receptors and their function. Neuropharmacology.1999;38:1083– 1152; and Cuomo A., Bianchetti A, Cagnin A. et al: Trazodone: a multifunctional antidepressant. Evaluation of its properties and real-world use. JGG. 2021;69:120-129. doi: 10.36150 / 2499-6564-N320.

[0021] Thus, in view of this SD treatment deficiency, there are definite needs for new treatments for SD, especially orally administered SD drugs, that can be used alone or in combination use with other SD drugs, for improving, inter alia, sexual desire, sexual function, sexual interest, subjective state of well-being, self-esteem, and / or self- confidence, SUMMARY OF THE INVENTION

[0022] In one aspect, the invention provides compositions and methods for treating a subject suffering from or susceptible to a sexual disorder or dysfunction or a symptom thereof (SD), e.g., FSD, MSD, HSDD, FSAD, FOD, FSIAD, FSPD, MSD, MHSDD, ED, PD, MPE, MDE, MDL, and / or MDO, in subjects with such a sexual dysfunction or disorder (each defined herein), and the like, comprising administering to the subject a therapeutically effective amount of a composition delineated herein for improving the subject’s SD.

[0023] In one aspect, the invention provides compositions and methods for treating a subject who needs or desires to improve his or her sexual function comprising administering to the subject a therapeutically effective amount of a composition delineated herein for improving the subject’s sexual function.

[0024] In one aspect, the invention provides compositions and methods for treating a subject suffering with sexual disorder or sexual dysfunction (SD) who needs or desires to improve his or her SD comprising administering to the subject a therapeutically effective amount of a composition delineated herein for improving the subject’s SD.Attorney Docket No.49848-4040PCT

[0025] In one aspect, the invention provides compositions and methods for treating a subject suffering with sexual interest / arousal disorder (SIAD) who needs or desires to improve his or her SIAD comprising administering to the subject a therapeutically effective amount of a composition delineated herein for improving the subject’s SIAD.

[0026] In one aspect, the invention provides compositions and methods for treating a subject suffering with female sexual dysfunction (FSD) who needs or desires to improve her FSD comprising administering to the subject a therapeutically effective amount of a composition delineated herein for improving the subject’s FSD.

[0027] In one aspect, the invention provides compositions and methods for treating a subject suffering with female hypoactive sexual desire disorder (FHSDD) who needs or desires to improve her FHSDD comprising administering to the subject a therapeutically effective amount of a composition delineated herein for improving the subject’s FHSDD.

[0028] In one aspect, the invention provides compositions and methods for treating a subject suffering with female sexual interest / arousal disorder (FSIAD) who needs or desires to improve her FSIAD comprising administering to the subject a therapeutically effective amount of a composition delineated herein for improving the subject’s FSIAD.

[0029] In one aspect, the invention provides compositions and methods for treating a subject suffering with female sexual arousal disorder (FSAD) who needs or desires to improve her FSAD comprising administering to the subject a therapeutically effective amount of a composition delineated herein for improving the subject’s FSAD.

[0030] In one aspect, the invention provides compositions and methods for treating a subject suffering with female orgasmic disorder (FOD) who needs or desires to improve her FOD comprising administering to the subject a therapeutically effective amount of a composition delineated herein for improving the subject’s FOD.

[0031] In one aspect, the invention provides compositions and methods for treating a subject suffering with female sexual pain disorder (FSPD) who needs or desires toAttorney Docket No.49848-4040PCT improve her FSPD comprising administering to the subject a therapeutically effective amount of a composition delineated herein for improving the subject’s FSPD.

[0032] In one aspect, the invention provides compositions and methods for treating a subject suffering with male sexual disorder (MSD) who needs or desires to improve his MSD comprising administering to the subject a therapeutically effective amount of a composition delineated herein for improving the subject’s MSD.

[0033] In one aspect, the invention provides compositions and methods for treating a subject suffering with male hyposexual desire disorder (MHSDD) who needs or desires to improve his MHSDD comprising administering to the subject a therapeutically effective amount of a composition delineated herein for improving the subject’s MHSDD.

[0034] In one aspect, the invention provides compositions and methods for treating a subject suffering with erectile dysfunction (ED) who needs or desires to improve his ED comprising administering to the subject a therapeutically effective amount of a composition delineated herein for improving the subject’s ED.

[0035] In one aspect, the invention provides compositions and methods for treating a subject suffering with Pyronine’s disease (PD) who needs or desires to improve his PD comprising administering to the subject a therapeutically effective amount of a composition delineated herein for improving the subject’s PD.

[0036] In one aspect, the invention provides compositions and methods for treating a subject suffering with male premature ejaculation (MPE) who needs or desires to improve his MPE comprising administering to the subject a therapeutically effective amount of a composition delineated herein for improving the subject’s MPE.

[0037] In one aspect, the invention provides compositions and methods for treating a subject suffering with male delayed ejaculation (MDE) who needs or desires to improve his MDE comprising administering to the subject a therapeutically effective amount of a composition delineated herein for improving the subject’s MDE.Attorney Docket No.49848-4040PCT

[0038] In one aspect, the invention provides compositions and methods for treating a subject suffering with male decreased libido (MDL) who needs or desires to improvement in his MDL comprising administering to the subject a therapeutically effective amount of a composition delineated herein for improving the subject’s MDL.

[0039] In one aspect, the invention provides compositions and methods for treating a subject suffering with male dry orgasm (MDO) who needs or desires to improve his MDO comprising administering to the subject a therapeutically effective amount of a composition delineated herein for improving the subject’s MDO.

[0040] ting a subject for a sexual disorder or sexual dysfunction or a symptom thereof, namely, SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FSPD, MSD, MHSDD, ED, PD, MPE, MDE, MDL, and / or MDO, and the like comprising administering to the subject a therapeutically effective amount of a composition delineated herein for improving the SD and effecting weight loss in the subject.

[0041] Disclosed are pharmaceutical compositions for improving SD, as well as inducing weight loss, comprising first and second compounds, wherein the first compound is bupropion, or a pharmaceutically acceptable salt thereof, and the second compound is trazodone, or a pharmaceutically acceptable salt thereof.

[0042] The combination is preferably an oral, non-hormonal, preferably, a fixed-dose combination of sustained release bupropion, or its pharmaceutically acceptable salt, and sustained release trazodone, or its pharmaceutically acceptable salt.

[0043] In accordance with the present invention, the oral, non-hormonal, fixed-dose combinations of sustained release bupropion, or its pharmaceutically acceptable salt, and the sustained release trazodone, or its pharmaceutically acceptable salt are preferably formulated as a single composite fixed dose pharmaceutical dosage form for single fixed- dose oral administration.Attorney Docket No.49848-4040PCT

[0044] Alternatively, and in accordance with the present invention, the oral, non-hormonal, fixed-dose combination of sustained release bupropion, or its pharmaceutically acceptable salt, and sustained release trazodone, or its pharmaceutically acceptable salt may each be formulated into their own separate fixed-dose pharmaceutical dosage forms for dual fixed-dose oral administration of the bupropion and trazodone, respectively.

[0045] Also disclosed herein are methods of providing obesity or weight loss therapy or weight loss maintenance therapy for those subjects who are inflicted with or suffering from SD.

[0046] More particularly, disclosed are methods for improving sexual desire and sexual function, improving subjective state of well-being, self-esteem, and / or self-confidence while concurrently inducing and / or maintaining weight loss, enhancing energy, and improving sleep.

[0047] In some embodiments, the combination of bupropion and trazodone unexpectedly improves SD and induces weight loss in subjects suffering from being overweight or obese or who desire to lose weight

[0048] In a four-week open label study of subjects suffering with HSDD, the combination of sustained release (SR) bupropion and sustained release (SR) trazodone were highly tolerable with minimal side effects and, quite surprisingly and unexpectedly, the combination induced weight loss in about 71% of the patients and demonstrated about a 38% stronger HSDD efficacy than the use of bupropion alone. Of the weight loss responders, 50% had an average weight loss of about 5.1%, 25% of the responders experienced ≥ 6% weight loss, and a maximum weight loss achieved was about 10.2%. Both the weight loss results and the HSDD results are quite remarkable.

[0049] In some embodiments, for subjects who suffer with SD or SD symptoms and obesity, being overweight, carrying undesirable weight and / or struggling with weight maintenance, the combination of bupropion and trazodone of the present inventionAttorney Docket No.49848-4040PCT unexpectedly improves their sexual disorder or dysfunction (SD), e.g., low of no sexual desire, low or no sexual fantasies, low or no sexual interest, low or no sexual arousal, and / or orgasmic dysfunction, i.e., a diminished frequency and / or intensity in orgasms, while simultaneously treating their obesity and / or weight issues by inducing their weight loss and / or maintaining their weight. In further embodiments, following their SD improvement and weight loss and / or weight maintenance effectuated by the combination treatments of the present invention, such combinations also improve the subjects’ subjective state of well-being, self-esteem, and / or self-confidence.

[0050] In some embodiments, the combinations of bupropion and trazodone mproves SD and induces weight loss in patients suffering from being overweight, being obese or carrying undesirable weight and improves their sense of subjective well-being, self- esteem, and / or self-confidence due to improved energy and sleep.

[0051] In one aspect, the invention provides compositions and methods for treating a subject who needs SD treatment and who needs, desires or has been instructed by a health provider to lose weight comprising administering to the subject a therapeutically effective amount of a composition delineated herein for effectuating SD improvement and the subject’s weight loss.

[0052] In one aspect, the invention provides compositions and methods for treating a subject who needs SD treatment and who needs, desires or has been instructed by a health provider to maintain weight whether or not the weight maintenance follows weight loss by the subject comprising administering to the subject a therapeutically effective amount of a composition delineated herein for effectuating SD improvement and the subject’s weight loss.

[0053] In some embodiments, the combination of bupropion and trazodone treats and improves both sexual disorder or sexual dysfunction (SD) and overweight, obesity and / or weight loss.Attorney Docket No.49848-4040PCT

[0054] In some embodiments, the combination of bupropion and trazodone treats and improves sexual disorder or sexual dysfunction (SD), overweight, obesity or weight loss, and the sense of subjective well-being, self-esteem, and / or self-confidence.

[0055] In some embodiments, the combination of bupropion and trazodone treats and improves both sexual function and overweight, obesity and / or weight loss.

[0056] In some embodiments, the combination of bupropion and trazodone treats and improves sexual function, overweight, obesity or weight loss, and the sense of subjective well-being, self-esteem, and / or self-confidence.

[0057] In some embodiments, the combination of bupropion and trazodone treats and improves both overweight, obesity and / or weight loss and female sexual dysfunction (“FSD”).

[0058] In some embodiments, the combination of bupropion and trazodone treats and improves overweight, obesity and / or weight loss and hyposexual desire disorder (HSDD).

[0059] In some embodiments, the combination of bupropion and trazodone treats and improves both overweight, obesity and / or weight loss and female sexual arousal disorder (FSAD).

[0060] In some embodiments, the combination of bupropion and trazodone treats and improves both overweight, obesity and / or weight loss and female orgasmic disorder (FOD).

[0061] In some embodiments, the combination of bupropion and trazodone treats and improves both overweight, obesity and / or weight loss and female pain disorder (FPD).

[0062] In some embodiments, the combination of bupropion and trazodone treats and improves both overweight, obesity and / or weight loss and male sexual dysfunction (MSD).Attorney Docket No.49848-4040PCT

[0063] In some embodiments, the combination of bupropion and trazodone treats and improves both overweight, obesity and / or weight loss and male hypoactive sexual desire disorder (MHSDD).

[0064] In some embodiments, the combination of bupropion and trazodone treats and improves both overweight, obesity and / or weight loss and erectile dysfunction (ED).

[0065] In some embodiments, the combination of bupropion and trazodone treats and improves both overweight, obesity and / or weight loss and Pyronine’s disease (PD).

[0066] In some embodiments, the combination of bupropion and trazodone treats and improves both overweight, obesity and / or weight loss and male premature ejaculation (MPE).

[0067] In some embodiments, the combination of bupropion and trazodone treats and improves both overweight, obesity and / or weight loss and male delayed ejaculation (MDE).

[0068] In some embodiments, the combination of bupropion and trazodone treats and improves both overweight, obesity and / or weight loss and male decreased libido (MDL).

[0069] In some embodiments, the combination of bupropion and trazodone treats and improves both overweight, obesity and / or weight loss and male dry orgasm (MDO).

[0070] In one aspect, the invention provides compositions and multi-function methods for treating a subject for a sexual disorder or sexual dysfunction or a symptom thereof, namely, SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FSPD, SIAD, MSD, MHSDD, ED, PD, MPE, MDE, MDL, and / or MDO, and for weight loss and / or weight maintenance comprising administering to the subject a therapeutically effective amount of a composition delineated herein for improving the SD and effectuating weight loss in the subject.Attorney Docket No.49848-4040PCT

[0071] In one aspect, the invention provides compositions and further multi-function methods for treating a subject for a sexual disorder or dysfunction or a symptom thereof, namely, SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FSPD, SIAD, MSD, MHSDD, ED, PD, MPE, MDE, MDL, and / or MDO, for weight loss and / or weight maintenance, and for poor or low subjective state of well-being, self-esteem and / or self- confidence comprising administering to the subject a therapeutically effective amount of a composition delineated herein for improving the SD and effectuating weight loss in the subject.

[0072] In some embodiments, the combination of bupropion and trazodone unexpectedly (1) induces weight loss in obese or overweight subjects or subjects desiring to lose weight, and (2) improves sexual disorder or dysfunction (SD), e.g., improves the symptoms of SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FSPD, SIAD, MSD, MHSDD, ED, PD, MPE, MDE, MDL, and / or MDO, in subjects with such a sexual dysfunction or disorder, and / or (3) improves subjective state of well-being, self-esteem, and / or self- confidence in subjects who have or are suffering from a state, condition, or sense of poor or low or lack of subjective well-being, self-esteem, and / or self-confidence.

[0073] In some embodiments, the combination of bupropion and trazodone treats and induces and / or maintains weight loss, improves SD symptoms and improves a state, condition, or sense of poor or low or lack of subjective well-being, self-esteem, and / or self-confidence

[0074] In some embodiments, the combination of bupropion and trazodone treats and induces and / or maintains weight loss, improves FSD symptoms and improves a state, condition, or sense of poor or low or lack of subjective well-being, self-esteem, and / or self-confidence.

[0075] In some embodiments, the combination of bupropion and trazodone treats and induces and / or maintains weight loss, improves HSDD symptoms and improves a state, condition, or sense of poor or low or lack of subjective well-being, self-esteem, and / or self-confidence.Attorney Docket No.49848-4040PCT

[0076] In some embodiments, the combination of bupropion and trazodone treats and induces and / or maintains weight loss, improves HSIAD symptoms and improves a state, condition, or sense of poor or low or lack of subjective well-being, self-esteem, and / or self-confidence.

[0077] In some embodiments, the combination of bupropion and trazodone treats and induces and / or maintains weight loss, improves FSAD symptoms and improves a state, condition, or sense of poor or low or lack of subjective well-being, self-esteem, and / or self-confidence.

[0078] In some embodiments, the combination of bupropion and trazodone treats and induces and / or maintains weight loss, improves FOD symptoms and improves a state, condition, or sense of poor or low or lack of subjective well-being, self-esteem, and / or self-confidence.

[0079] In some embodiments, the combination of bupropion and trazodone treats and induces and / or maintains weight loss, improves FSP symptoms and improves a state, condition, or sense of poor or low or lack of subjective well-being, self-esteem, and / or self-confidence.

[0080] In some embodiments, the combination of bupropion and trazodone treats and induces and / or maintains weight loss, improves SIAD symptoms and improves a state, condition, or sense of poor or low or lack of subjective well-being, self-esteem, and / or self-confidence.

[0081] In some embodiments, the combination of bupropion and trazodone treats and induces and / or maintains weight loss, improves MSD symptoms and improves a state, condition, or sense of poor or low or lack of subjective well-being, self-esteem, and / or self-confidence.Attorney Docket No.49848-4040PCT

[0082] In some embodiments, the combination of bupropion and trazodone treats and induces and / or maintains weight loss, improves MHSDD symptoms and improves a state, condition, or sense of poor or low or lack of subjective well-being, self-esteem, and / or self-confidence

[0083] In some embodiments, the combination of bupropion and trazodone treats and induces and / or maintains weight loss, improves ED symptoms and improves a state, condition, or sense of poor or low or lack of subjective well-being, self-esteem, and / or self-confidence.

[0084] In some embodiments, the combination of bupropion and trazodone treats and induces and / or maintains weight loss, improves PD symptoms and improves a state, condition, or sense of poor or low or lack of subjective well-being, self-esteem, and / or self-confidence.

[0085] In some embodiments, the combination of bupropion and trazodone treats and induces and / or maintains weight loss, improves MPE symptoms and improves a state, condition, or sense of poor or low or lack of subjective well-being, self-esteem, and / or self-confidence.

[0086] In some embodiments, the combination of bupropion and trazodone treats and induces and / or maintains weight loss, improves MDE symptoms and improves a state, condition, or sense of poor or low or lack of subjective well-being, self-esteem, and / or self-confidence.

[0087] In some embodiments, the combination of bupropion and trazodone treats and induces and / or maintains weight loss, improves MDL symptoms and improves a state, condition, or sense of poor or low or lack of subjective well-being, self-esteem, and / or self-confidence.

[0088] In some embodiments, the combination of bupropion and trazodone treats and induces and / or maintains weight loss, improves MDO symptoms and improves a state,Attorney Docket No.49848-4040PCT condition, or sense of poor or low or lack of subjective well-being, self-esteem, and / or self-confidence.

[0089] In another aspect, the invention provides a composition comprising a 5-HT2A antagonist, a norepinephrine-dopamine reuptake inhibitor, and a pharmaceutically acceptable carrier. In another aspect the composition is that wherein the 5-HT2A antagonist is also a 5-HT1A receptor agonist. In another aspect the composition is that comprising trazodone and bupropion.

[0090] In one aspect, the invention provides a pharmaceutical composition comprising a 5-HT2A antagonist, e.g., trazodone, a norepinephrine-dopamine reuptake inhibitor, e.g., bupropion, and a pharmaceutically acceptable carrier. In another aspect the composition is both a 5-HT2A antagonist and a 5-HT1A receptor agonist. In another aspect the pharmaceutical composition comprises bupropion or a pharmaceutically acceptable salt thereof, and trazodone or a pharmaceutically acceptable salt thereof. In another aspect the composition is that comprising trazodone in a dosage range of 25-450 mg and bupropion in a dosage range of 200-450 mg. In another aspect the composition is that comprising trazodone in a dosage range of 25-450 mg and bupropion in a dosage range of 25-450 mg.

[0091] In one embodiment, the composition is that comprising bupropion, comprising bupropion in a dosage range of 200-450 mg; comprising bupropion in a dosage range of 225-300 mg; or comprising bupropion in a dosage range of 200-275 mg; comprising bupropion in a dosage range of 100-450 mg; comprising bupropion in a dosage range of 100-275 mg; comprising bupropion in a dosage range of 25-275 mg; comprising bupropion in a dosage range of XX-YY mg, wherein XX is an integer between 5 and 400 and YY is an integer between 50 and 450.

[0092] In one embodiment, the composition is that comprising trazodone, comprising trazodone in a dosage range of 25-450 mg; comprising trazodone in a dosage range of 75-150 mg; or comprising trazodone in a dosage range of 50-100 mg; comprisingAttorney Docket No.49848-4040PCT trazodone in a dosage range of XX-YY mg, wherein XX is an integer between 25 and 400 and YY is an integer between 50 and 450.

[0093] In one aspect, the invention provides a method of treating a subject suffering from or susceptible to a hypoactive sexual desire disorder (HSDD) comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising a 5-HT2A antagonist, a norepinephrine-dopamine reuptake inhibitor, and a pharmaceutically acceptable carrier. In one aspect, one compound is both a 5-HT2A antagonist and a 5-HT1A receptor agonist (e.g., trazodone). In another aspect, the norepinephrine-dopamine reuptake inhibitor is also a alpha adrenergic blocker (e.g., bupropion).

[0094] In one aspect, the invention provides a method of treating a subject suffering from or susceptible to a hypoactive sexual desire disorder (HSDD) comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising a 5-HT1A receptor agonist, a 5-HT2A antagonist, and a pharmaceutically acceptable carrier. In one aspect, one compound is the 5-HT1A receptor agonist and the 5-HT2A antagonist (e.g., trazodone).

[0095] In aspects, the method is that wherein the sexual disorder (SD) is female sexual disorder (FSD).

[0096] In aspects, the method is that wherein the SD is female orgasm disorder (FOD); wherein the SD is female sexual arousal disorder (FSAD); wherein the SD is female sexual interest / arousal disorder (FSIAD); wherein the SD is female hypoactive sexual desire disorder (HSDD); and / or wherein the SD is female sexual pain disorder or dysfunction (FSPD). In aspects, the method is that wherein the FSD includes one or more simultaneous dysfunctions of sexual desire, interest, arousal, orgasm, and / or pain.

[0097] Another aspect is a method of treating a subject for FSD, HSDD, FOD, FSAD, FSIAD, SAID, and / or FSPD comprising administering to the subject a compound or composition herein.Attorney Docket No.49848-4040PCT

[0098] In aspects, the method is that wherein the SD is male sexual disorder (MSD). In aspects, the method is that wherein the MSD is male hypoactive sexual desire disorder (MHSDD); wherein the MSD is erectile dysfunction (ED); wherein the MSD is Pyronine’s disease (PD); wherein the MSD is male premature ejaculation (MPE); wherein the MSD is male delayed ejaculation (MDE); wherein the MSD is male decreased libido (MDL); and / or wherein the MSD is male dry orgasm (MDO).

[0099] Another aspect is a method of treating a subject for MSD, MHSDD, ED, PD, MPE, MDE, MDL, MDO, and / or SAID comprising administering to the subject a compound or composition herein.

[0100] In some embodiments, the methods unexpectedly provide the same amount of weight loss combination drug dosages for obese patients who are suffering from lack of sexual desire and / or sexual function or low or poor or a lack of a subjective state of well-being, self-esteem, and / or self-confidence as in obese patients who are not suffering from a lack of sexual desire and / or sexual function or low or poor or lack of a subjective state of well-being, self-esteem, and / or self-confidence. In some embodiments, the dosages of bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof unexpectedly treat both obesity and lack of sexual desire and / or sexual function, and / or a low or poor or lack of a subjective state of well-being self-esteem, and / or self-confidence.

[0101] In some embodiments, the methods unexpectedly provide the same amount of weight loss combination drug dosages for overweight patients who are suffering from a lack of sexual desire and / or sexual function or a low or poor or lack of a subjective state of well-being, self-esteem, and / or self-confidence swings as in overweight patients who are not suffering from a lack of sexual desire and sexual function or a low or poor or lack of a subjective state of well-being, self-esteem, and / or self- confidence swings.Attorney Docket No.49848-4040PCT

[0102] In some embodiments, the dosages of bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof treat both overweight, a lack of sexual desire, lack of sexual interest, lack of sexual desire, lack of sexual fantasies, and / or a lack of sexual function, and / or a subjective state of low or poor or lack of well-being, self-esteem, and / or self-confidence.

[0103] In some embodiments, the dosages of bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof treat obesity, SD and / or a subjective state of low or poor or lack of well-being, self-esteem, and / or self-confidence.

[0104] In some embodiments, the dosages of bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof treat overweight, SD and / or a subjective state of low or poor or lack of well-being, self-esteem, and / or self-confidence.

[0105] In some embodiments, the dosages of bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof unexpectedly treat undesired weight, SD and / or a subjective state of low or poor or lack of well-being, self-esteem, and / or self-confidence.

[0106] In some embodiments, the dosages of bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof unexpectedly treat weight loss maintenance, SD and / or a subjective state of low or poor or lack of well-being, self-esteem, and / or self-confidence.

[0107] In some embodiments, a method for providing weight loss therapy to a patient is provided, comprising: identifying a patient suffering from SD, such as FSD, HSDD, FSAD, FOD, FSIAD, FSP, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, wherein the patient is also overweight, obese or carrying undesired weight; and reducing weight of the patient in need of SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FSP, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE,Attorney Docket No.49848-4040PCT MDL, MDO, and the like, and weight loss treatment by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the trazodone or a pharmaceutically acceptable salt thereof is in an amount effective to enhance the weight loss activity of the bupropion or a pharmaceutically acceptable salt thereof, the bupropion or a pharmaceutically acceptable salt thereof is in an amount effective to enhance the weight loss activity of the trazodone or a pharmaceutically acceptable salt thereof, or the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are each in amounts effective to enhance the weight loss activity of one another, and wherein the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are in amounts believed to restore the balance of the three neurotransmitters that are known to regulate sexual inhibition and sexual excitation, i.e., dopamine, serotonin and norepinephrine, so that the treated patient loses weight and the patient’s sexual desire, sexual fantasies, and / or sexual function are improved or restored.

[0108] In some embodiments, a method for providing weight loss therapy to a patient is provided, comprising: identifying a patient suffering from a low or poor or lack of a state, condition, or sense of subjective well-being and / or self-esteem, wherein the patient is also overweight, obese or carrying undesired weight; and reducing weight of the patient in need of subjective well-being, self-esteem, and / or self-confidence and weight loss treatment by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the trazodone or a pharmaceutically acceptable salt thereof is in an amount effective to enhance the weight loss activity of the bupropion or a pharmaceutically acceptable salt thereof, the bupropion or a pharmaceutically acceptable salt thereof is in an amount effective to enhance the weight loss activity or effect of the trazodone or a pharmaceutically acceptable salt thereof, or the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are each in amounts effective to enhance the weight loss activity of one another, and wherein the bupropion or a pharmaceutically acceptable salt thereof and the trazodoneAttorney Docket No.49848-4040PCT or a pharmaceutically acceptable salt thereof are in amounts believed to regulate and / or improve the patient’s subjective state of well-being, self-esteem, and / or self-confidence by increasing and / or balancing the norepinephrine and dopamine hormone levels in the patient’s brain to shift or improve the patient’s subjective state or sense of well-being, self- esteem, and / or self-confidence.

[0109] In certain embodiments, the method further comprises adjusting the dosage of the bupropion or a pharmaceutically acceptable salt thereof, the trazodone or a pharmaceutically acceptable salt thereof, or both as needed to treat the patient's overweight, obesity or undesired weight. In certain embodiments, the method further comprises adjusting the dosage of the bupropion or a pharmaceutically acceptable salt thereof, the trazodone or a pharmaceutically acceptable salt thereof, or both as needed to treat the patient's sexual inhibition. In certain embodiments, the method further comprises adjusting the dosage of the trazodone or pharmaceutically acceptable salt thereof, the bupropion or pharmaceutically acceptable salt thereof, or both as needed to treat the patient's lack of sexual desire, sexual fantasies and / or sexual function. In certain embodiments, the method further comprises adjusting the dosage of the bupropion or a pharmaceutically acceptable salt thereof, the trazodone or a pharmaceutically acceptable salt thereof, or both as needed to treat the patient's SD. In certain embodiments, the method further comprises adjusting the dosage of the bupropion or a pharmaceutically acceptable salt thereof, the trazodone or a pharmaceutically acceptable salt thereof, or both as needed to treat the patient's SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FSP, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like. In certain embodiments, the method further comprises adjusting the dosage of the bupropion or a pharmaceutically acceptable salt thereof, the trazodone or a pharmaceutically acceptable salt thereof, or both as needed to treat the patient's low or poor or lack of a subjective state of well-being, self-esteem, and / or self-confidence. In certain embodiments, the patient is a woman. In certain embodiments, the patient is a man. In certain embodiments, the method further comprises administering the bupropion or a pharmaceutically acceptable salt thereof and bupropion trazodone or a pharmaceutically acceptable salt thereof with food. In certain embodiments, at least oneAttorney Docket No.49848-4040PCT of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof is in a modified release delayed release formulation. In certain embodiments, the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are in a modified release or delayed release formulation. In certain embodiments, the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are in the same pharmaceutical composition. In certain embodiments, the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are in separate pharmaceutical compositions.

[0110] In certain embodiments, the SD treating combination is administered once per day or more than once per day. In certain embodiments, the SD treating combination is administered acutely or chronically such as for a period of at least 3 months or longer. In certain embodiments, the SD treating combination is administered for a chronic period of at least 4 or 5 months. In certain embodiments, the SD treating combination is administered for a chronic period of at least 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months or longer, or however long to accomplish the designated SD treatment objectives n accordance with the present invention.

[0111] In certain embodiments, the SD treating combination is administered once per day or more than once per day as monotherapy.

[0112] In certain embodiments, the bupropion or a pharmaceutically acceptable salt thereof is administered prior or subsequent to the trazodone or a pharmaceutically acceptable salt thereof. In certain embodiments, the bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and the trazodone or a pharmaceutically acceptable salt thereof is administered at night. In certain embodiments, the bupropion or a pharmaceutically acceptable salt thereof isAttorney Docket No.49848-4040PCT administered twice daily, once in the morning and once at night, and the trazodone or a pharmaceutically acceptable salt thereof is administered once daily at night.

[0113] In certain embodiments, the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are co- administered or administered together once per day.

[0114] In certain embodiments, the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are both in sustained release form.

[0115] In certain embodiments, the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are in a single oral dosage form. In certain embodiments, the single oral dosage form further comprises a pharmaceutically acceptable excipient, diluent, or carrier. In certain embodiments, the single oral dosage form is a modified release or delayed release oral dosage form. In certain embodiments, the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are each in sustained release form within the single oral dosage form.

[0116] Another aspect is a method of treating a disease, disorder or symptom thereof described in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) in a subject comprising administering to the subject a compound or composition herein.

[0117] Another aspect is an extended-release composition comprising a 5-HT2A antagonist, a norepinephrine-dopamine reuptake inhibitor, and a pharmaceutically acceptable carrier.

[0118] In one aspect, the invention provides a composition comprising the 5-HT1A receptor agonist and 5-HT2A antagonist nefazodone and a pharmaceutically acceptable carrier.Attorney Docket No.49848-4040PCT

[0119] In one aspect, the invention provides a composition comprising the 5-HT1A receptor agonist and 5-HT2A antagonist mirtazapine and a pharmaceutically acceptable carrier.

[0120] Other aspects include those, wherein the composition is administered orally; wherein the composition is administered topically; wherein the subject is diagnosed and being treated for depression; wherein the subject is not undergoing treatment for depression; wherein the subject is concurrently prescribed an additional therapeutic agent; or wherein the subject is concurrently not prescribed an additional therapeutic agent; wherein the subject is concurrently administered an additional therapeutic agent; or wherein the subject is concurrently not administered an additional therapeutic agent.

[0121] In one aspect, the invention provides a composition comprising a 5-HT1A receptor agonist, a 5-HT2A antagonist, and a pharmaceutically acceptable carrier.

[0122] In one embodiment, the composition is that comprising bupropion, comprising bupropion in a dosage range of 100-450 mg qd; comprising bupropion in a dosage range of 200-450 mg qd; comprising bupropion in a dosage range of 100-300 mg qd; comprising bupropion in a dosage range of 225-300 mg qd; comprising bupropion in a dosage range of 100-275 mg qd; or comprising bupropion in a dosage range of 200- 275 mg qd; comprising bupropion in a dosage range of XX-YY mg qd, wherein XX is an integer between 5 and 400 and YY is an integer between 50 and 450.

[0123] In one embodiment, the composition is that comprising trazodone, comprising trazodone in a dosage range of 25-450 mg qd; comprising trazodone in a dosage range of 75-150 mg qd; or comprising trazodone in a dosage range of 50-100 mg qd; comprising trazodone in a dosage range of XX-YY mg qd, wherein XX is an integer between 25 and 400 and YY is an integer between 50 and 450.

[0124] In one embodiment, the composition is that comprising bupropion and trazodone, comprising bupropion in a dosage range of 50-450 mg and trazodone in aAttorney Docket No.49848-4040PCT dosage range of 25-450 mg; comprising bupropion in a dosage range of 200-450 mg and trazodone in a dosage range of 25-450 mg; comprising bupropion in a dosage range of 100-300 mg qd and comprising trazodone in a dosage range of 75-150 mg qd; comprising bupropion in a dosage range of 225-300 mg qd and comprising trazodone in a dosage range of 75-150 mg qd; comprising bupropion in a dosage range of 100-275 mg qd and comprising trazodone in a dosage range of 50-100 mg qd; or comprising bupropion in a dosage range of 200-275 mg qd and comprising trazodone in a dosage range of 50-100 mg qd.

[0125] In one aspect, the invention provides a method of making a composition comprising combining a 5-HT2A antagonist, a norepinephrine-dopamine reuptake inhibitor, and a pharmaceutically acceptable carrier. In one aspect, the invention provides a method of making a composition comprising combining a 5-HT1A receptor agonist, a 5- HT2A antagonist, and a pharmaceutically acceptable carrier. In one aspect, the invention provides a method of making a composition comprising combining a 5-HT1A receptor agonist, and a pharmaceutically acceptable carrier. In one aspect, the invention provides a method of making a composition comprising combining a 5-HT2A antagonist, and a pharmaceutically acceptable carrier.

[0126] In one aspect, the method of making a composition comprises combining a 5-HT1A receptor agonist, a norepinephrine-dopamine reuptake inhibitor and a pharmaceutically acceptable carrier such that the composition comprises a range of 25- 450 of a 5-HT1A receptor agonist. In another aspect, the method of making comprises combining a 5-HT2A antagonist and a pharmaceutically acceptable carrier such that the composition comprises a range of 25-450 mg of a 5-HT2A antagonist and a norepinephrine-dopamine reuptake inhibitor.

[0127] In one embodiment, the method comprises combining bupropion, trazodone, and a pharmaceutically acceptable carrier.Attorney Docket No.49848-4040PCT

[0128] In some embodiments, a method for providing weight loss therapy to a patient is provided, comprising: identifying a patient who is suffering from In some embodiments, when treating a patient SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is in the range of about 326 mg to about 374 mg per day, wherein the amount of the trazodone or a pharmaceutically acceptable salt thereof is in the range of from about 124 mg to about 147 mg per day, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single modified release or delayed release formulation, (ii) each in their own separate modified release or delayed release dosage forms, or (iii) each are in their own separate modified release or delayed release formulations in a single dosage form.

[0129] In some embodiments, a method for providing SD therapy to a patient is provided, comprising: identifying a patient who is suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is in the range of about 366 mg to about 374 mg per day, wherein the amount of the trazodone or a pharmaceutically acceptable salt thereof is in the range of from about 139 mg to about 147 mg per day, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single modified release or delayed release formulation, (ii) each in their own separate modified release or delayed release dosage forms, or (iii) each are in their own separate modified release or delayed release formulations in a single dosage form.Attorney Docket No.49848-4040PCT

[0130] In some embodiments, a method for providing SD therapy to a patient is provided, comprising: identifying a patient who is suffering from In some embodiments, when treating a patient SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is about 369.5 mg per day, wherein the amount of the trazodone or a pharmaceutically acceptable salt thereof is about 143.5 mg per day, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single modified release or delayed release formulation, (ii) each in their own separate modified release or delayed release dosage forms, or (iii) each are in their own separate modified release or delayed release formulations in a single dosage form.

[0131] In some embodiments, a method for providing SD therapy to a patient is provided, comprising: identifying a patient who is suffering from In some embodiments, when treating a patient SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is in the range of about 326 mg to about 334 mg per day, wherein the amount of the trazodone or a pharmaceutically acceptable salt thereof is in the range of from about 124 mg to about 132 mg per day, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single modified release or delayed release formulation, (ii) each in their own separate modified release or delayed release dosage forms, or (iii) each are in their own separate modified release or delayed release formulations in a single dosage form.Attorney Docket No.49848-4040PCT

[0132] In some embodiments, a method for providing SD therapy to a patient is provided, comprising: identifying a patient who is suffering from In some embodiments, when treating a patient said SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is about 329.5 mg per day, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is about 128.5 mg per day, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single modified release or delayed release formulation, (ii) each in their own separate modified release or delayed release dosage forms, or (iii) each are in their own separate modified release or delayed release formulations in a single dosage form.

[0133] In some embodiments, when treating a patient for SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, the preferred amount of the bupropion or pharmaceutically acceptable salt thereof is in the range of about 366 mg to about 374 mg per day, and the preferred amount of the trazodone or a pharmaceutically acceptable salt thereof is in the range of from about 139 mg to about 147 mg per day.

[0134] In some embodiments, when treating a patient for SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, the preferred amount of the bupropion or pharmaceutically acceptable salt thereof is about 369.5 mg per day and the preferred amount of the trazodone or a pharmaceutically acceptable salt thereof is about 143.5 mg per day.

[0135] In some embodiments, when treating a patient for SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, the preferred amount of the bupropion or pharmaceuticallyAttorney Docket No.49848-4040PCT acceptable salt thereof is in the range of about 326 mg to about 334 mg per day, wherein the preferred amount of the trazodone or a pharmaceutically acceptable salt thereof is in the range of from about 124 mg to about 132 mg per day.

[0136] In some embodiments, when treating a patient for SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, the preferred amount of the bupropion or pharmaceutically acceptable salt thereof is about 329.5 mg per day and the preferred amount of the trazodone or a pharmaceutically acceptable salt thereof is about 128.5 mg per day.

[0137] In some embodiments, a method for providing SD therapy to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is in the range of about 326 mg to about 374 mg per day, wherein the amount of the trazodone or a pharmaceutically acceptable salt thereof is in the range of from about 124 mg to about 147 mg per day, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0138] In some embodiments, a method for providing SD therapy to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropionAttorney Docket No.49848-4040PCT or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is in the range of about 366 mg to about 374 mg per day, wherein the amount of the trazodone or a pharmaceutically acceptable salt thereof is in the range of from about 139 mg to about 147 mg per day, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0139] In some embodiments, a method for providing SD therapy to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is about 369.5 mg per day, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is about 143.5 mg per day, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0140] In some embodiments, a method for providing SD therapy to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD,Attorney Docket No.49848-4040PCT FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is in the range of about 326 mg to about 334 mg per day, wherein the amount of the trazodone or a pharmaceutically acceptable salt thereof is in the range of from about 124 mg to about 132 mg per day, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0141] In some embodiments, a method for providing SD therapy to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is about 329.5 mg per day, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is about 128.5 mg per day, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.Attorney Docket No.49848-4040PCT

[0142] In some embodiments, a method for providing SD therapy to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof,, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is in the range of about 200 mg to about 400 mg per day, wherein the amount of the trazodone or a pharmaceutically acceptable salt thereof is in the range of from about 50 mg to about 150 mg per day, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0143] In some embodiments, a method for providing SD therapy to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 250 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and wherein about 100 mg of bupropion or a pharmaceutically acceptable salt thereof is administered at night or at bedtime, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 75 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in theirAttorney Docket No.49848-4040PCT own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0144] In some embodiments, a method for providing SD therapy to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 150 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 75 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0145] In some embodiments, a method for providing SD therapy to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 250 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and whereinAttorney Docket No.49848-4040PCT about 100 mg of bupropion or a pharmaceutically acceptable salt thereof is administered at night or at bedtime, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 150 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0146] In some embodiments, a method for providing SD therapy to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 150 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 150 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0147] In some embodiments, a method for providing SD therapy to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD,Attorney Docket No.49848-4040PCT FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 300 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered at night or at bedtime, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 75 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0148] In some embodiments, a method for providing SD therapy to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 300 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered at night or at bedtime, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 150 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in theirAttorney Docket No.49848-4040PCT own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0149] In some embodiments, a method for providing SD therapy to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 250 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and wherein about 100 mg of bupropion or a pharmaceutically acceptable salt thereof is administered at night or at bedtime, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 75 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0150] In some embodiments, a method for providing SD therapy to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 250 mg, wherein about 150 mg of bupropion or aAttorney Docket No.49848-4040PCT pharmaceutically acceptable salt thereof is administered in the morning and wherein about 100 mg of bupropion or a pharmaceutically acceptable salt thereof is administered at night or at bedtime, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 150 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0151] In some embodiments, a method for providing SD therapy to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 150 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 75 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.Attorney Docket No.49848-4040PCT

[0152] In some embodiments, a method for providing SD therapy to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 150 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 150 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0153] In some embodiments, a method for providing SD therapy to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 300 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered at night or at bedtime, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 75 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified releaseAttorney Docket No.49848-4040PCT or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0154] In some embodiments, a method for providing SD therapy to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like; and improving the patient’s said SD by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 300 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered at night or at bedtime, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 150 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0155] In some embodiments, a method for providing SD therapy, weight loss therapy or both to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, and / or having low or poor or lack of a subjective state or sense of well-being, self-esteem, and / or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducingAttorney Docket No.49848-4040PCT weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is in the range of about 326 mg to about 374 mg per day, wherein the amount of the trazodone or a pharmaceutically acceptable salt thereof is in the range of from about 124 mg to about 147 mg per day, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0156] In some embodiments, a method for providing SD therapy, weight loss therapy or both to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, and / or having low or poor or a lack of a subjective state or sense of well-being, self-esteem, and / or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is in the range of about 366 mg to about 374 mg per day, wherein the amount of the trazodone or a pharmaceutically acceptable salt thereof is in the range of from about 139 mg to about 147 mg per day, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separatelyAttorney Docket No.49848-4040PCT together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0157] In some embodiments, a method for providing SD therapy, weight loss therapy or both to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, and / or having low or poor or lack of a subjective state or sense of well-being, self-esteem, and / or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is about 369.5 mg per day, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is about 143.5 mg per day, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0158] In some embodiments, a method for providing SD therapy, weight loss therapy or both to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, and / or having low or poor or a lack of a subjective state or sense of well-being, self-esteem, and / or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is in theAttorney Docket No.49848-4040PCT range of about 326 mg to about 334 mg per day, wherein the amount of the trazodone or a pharmaceutically acceptable salt thereof is in the range of from about 124 mg to about 132 mg per day, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0159] In some embodiments, a method for providing SD therapy, weight loss therapy or both to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, and / or having low or poor or lack of a subjective state or sense of well-being, self-esteem, and / or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is about 329.5 mg per day, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is about 128.5 mg per day, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.Attorney Docket No.49848-4040PCT

[0160] In some embodiments, a method for providing SD therapy, weight loss therapy or both to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, and / or having low or poor or lack of a subjective state or sense of well-being, self-esteem, and / or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof,, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is in the range of about 200 mg to about 400 mg per day, wherein the amount of the trazodone or a pharmaceutically acceptable salt thereof is in the range of from about 50 mg to about 150 mg per day, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0161] In some embodiments, a method for providing SD therapy, weight loss therapy or both to a patient is provided, comprising: identifying a patient suffering from obesity or being overweight or having undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 250 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and wherein about 100 mg of bupropion or a pharmaceutically acceptable salt thereof is administered at night or at bedtime, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 75 mg, and wherein each of the bupropion or aAttorney Docket No.49848-4040PCT pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0162] In some embodiments, a method for providing SD therapy, weight loss therapy or both to a patient is provided, comprising: identifying a patient suffering from obesity or being overweight or having undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 150 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 75 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0163] In some embodiments, a method for SD therapy, providing weight loss therapy or both to a patient is provided, comprising: identifying a patient suffering from obesity or being overweight or having undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the dailyAttorney Docket No.49848-4040PCT amount of the bupropion or a pharmaceutically acceptable salt thereof is about 250 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and wherein about 100 mg of bupropion or a pharmaceutically acceptable salt thereof is administered at night or at bedtime, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 150 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0164] In some embodiments, a method for providing SD therapy, weight loss therapy or both to a patient is provided, comprising: identifying a patient suffering from obesity or being overweight or having undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 150 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 150 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.Attorney Docket No.49848-4040PCT

[0165] In some embodiments, a method for providing SD therapy, weight loss therapy or both to a patient is provided, comprising: identifying a patient suffering from obesity or being overweight or having undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 300 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered at night or at bedtime, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 75 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0166] In some embodiments, a method for providing SD therapy, weight loss therapy or both to a patient is provided, comprising: identifying a patient suffering from obesity or being overweight or having undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 300 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered at night or at bedtime, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 150 mg, and wherein each of the bupropion orAttorney Docket No.49848-4040PCT a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0167] In some embodiments, a method for providing SD therapy, weight loss therapy or both to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like,, and / or having low or poor or lack of a subjective state or sense of well-being, self-esteem, and / or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 250 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and wherein about 100 mg of bupropion or a pharmaceutically acceptable salt thereof is administered at night or at bedtime, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 75 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.Attorney Docket No.49848-4040PCT

[0168] In some embodiments, a method for providing SD therapy, weight loss therapy or both to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like,, and / or having low or poor or lack of a subjective state or sense of well-being, self-esteem, and / or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 250 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and wherein about 100 mg of bupropion or a pharmaceutically acceptable salt thereof is administered at night or at bedtime, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 150 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0169] In some embodiments, a method for providing SD therapy, weight loss therapy or both to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like,, and / or having low or poor or lack of a subjective state or sense of well-being, self-esteem, and / or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereofAttorney Docket No.49848-4040PCT is about 150 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 75 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0170] In some embodiments, a method for providing SD, therapy, weight loss therapy or both to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like,, and / or having low or poor or lack of a subjective state or sense of well-being, self-esteem, and / or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 150 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 150 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separatelyAttorney Docket No.49848-4040PCT together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0171] In some embodiments, a method for providing SD therapy, weight loss therapy or both to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like,, and / or having low or poor or lack of a subjective state or sense of well-being, self-esteem, and / or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 300 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered at night or at bedtime, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 75 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0172] In some embodiments, a method for providing SD therapy, weight loss therapy or both to a patient is provided, comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, and / or having low or poor or lack of a subjective state or sense of well-being, self-esteem, and / or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducingAttorney Docket No.49848-4040PCT weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 300 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered at night or at bedtime, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 150 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single composite modified release or delayed release formulation for suitable oral administration, (ii) each formulated in their own separate modified release or delayed release dosage forms suitable for oral administration, or (iii) each are in their own separate modified release or delayed release formulation which are formulated separately together, without commingling of the bupropion and trazodone, into a single dosage form suitable for oral administration.

[0173] In certain embodiments, the method further comprises regulating and / or improving the patient’s low or poor or lack of a subjective state or sense of well-being, self-esteem, and / or self-confidence by increasing and / or balancing the norepinephrine and dopamine hormone levels in the patient’s brain to shift or improve the patient’s subjective state or sense of well-being, self-esteem, and / or self-confidence.

[0174] In some embodiments, a method for selecting a weight loss therapy from among available weight loss therapies is provided, comprising: evaluating a patient to assess whether the patient is simultaneously in need of weight loss therapy and depression therapy and / or or a subjective state or sense well-being, self-esteem, and / or self-confidence therapy; and if so, providing to the patient an effective weight-loss- inducing and antidepressant and / or a subjective state or sense of well-being, self-esteem, and / or self-confidence improvement combination of bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof as active ingredients. In certain embodiments, the method further comprises providingAttorney Docket No.49848-4040PCT printed information to the patient indicating that the combination promotes weight loss and reduces symptoms of depression and / or low or poor or lack of a subjective state or sense of well-being, self-esteem, and / or self-confidence. In certain embodiments, the patient has been diagnosed as suffering from major depressive disorder using the Montgomery-Asberg Depression Rating Scale (MADRS). In certain embodiments, the patient has been diagnosed as suffering from major depressive disorder using the Inventory of Depressive Symptomatology. In certain embodiments, the patient is not suffering from bipolar disorder. In certain embodiments, the patient is suffering from low or poor or lack of a subjective state or sense of well-being, self-esteem, and / or self- confidence. In certain embodiments, the patient is suffering from a sexual disorder. In certain embodiments, the patient is suffering from obesity or being overweight.

[0175] In one aspect, the invention provides a kit comprising a composition delineated herein and a label providing instructions for administration of the composition to a subject for treating or ameliorating SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, or any symptoms thereof in the subject.

[0176] In another aspect, the invention provides a method of treating SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, in a subject comprising administering to the subject a 5-HT1A receptor agonist, and a 5-HT2A antagonist. The methods herein can further comprise those wherein the subject is identified as in need of such treatment, and those wherein the subject is treated upon administration of the compounds and / or compositions herein. The methods can include those wherein the subject has not previously been administered the compounds and / or compositions herein, or wherein the subject has not previously been administered the compounds and / or compositions herein at the stated dosage levels or administration regimens.

[0177] In another embodiment, the invention a method of treating a subject suffering from or susceptible to a SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD,Attorney Docket No.49848-4040PCT and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising any one of a 5-HT2A antagonist, a norepinephrine-dopamine reuptake inhibitor, a 5-HT1A receptor agonist, an endocrine active agent, or any combination thereof and a pharmaceutically acceptable carrier.

[0178] In another aspect, the invention provides a method of treating SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, in a subject comprising administering to the subject a therapeutically effective amount of any one of a 5-HT2A antagonist, a norepinephrine-dopamine reuptake inhibitor, a 5-HT1A receptor agonist, an endocrine active agent, or any combination thereof.

[0179] In aspects the endocrine agent is testosterone, which can be in an amount of a dosage range of 25 to 1000 mg.

[0180] In aspects, the subject is that wherein the subject is not being treated with a selective serotonin reuptake inhibitor (SSRI) agent.

[0181] In aspects, the subject is that wherein the subject is being treated with a selective serotonin reuptake inhibitor (SSRI) agent.

[0182] In aspects, the subject is that wherein the subject is identified as having selective serotonin reuptake inhibitor (SSRI) agent induced HSDD, FSIAD, SIAD or MHSDD.

[0183] In aspects, the subject is that wherein the subject is being treated with a PDE-5 inhibitor compound (i.e., sildenafil, tadalafil, and the like).

[0184] In aspects, the subject is that wherein the subject is not concurrently being treated with a PDE-5 inhibitor compound (i.e., sildenafil, tadalafil, and the like).Attorney Docket No.49848-4040PCT

[0185] In aspects, the subject is that wherein the subject is being treated with an endocrine agent (e.g., testosterone).

[0186] In aspects, the subject is that wherein the subject is not concurrently being treated with an endocrine agent (e.g., testosterone).

[0187] In another aspect, the methods herein comprise taking a sample (i.e., fluid, blood, urine, saliva, tissue, etc.) and assessing a biological marker (i.e., liver enzymes, CYP3A4, and / or a genetic marker of the transport, receptor type, receptor density, receptor affinity, metabolism, or activity of serotonin, serotonin 1A or 2A subtype, dopamine, or a receptor subtype of dopamine) to measure health status of the subject either prior to, during or after administration of the compositions herein. DETAILED DESCRIPTION OF THE INVENTION

[0188] The present inventors have now discovered a therapeutic strategy that addresses SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, in a subject.

[0189] The present invention relates, at least in part, to the discovery that a combination of a 5-HT2A antagonist (which is optionally a 5-HT1A receptor agonist), a norepinephrine-dopamine reuptake inhibitor, (and optionally an endocrine active agent) provides unexpected superior and synergistic results in addressing SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, in a subject.

[0190] The present invention is directed to novel and unique compositions comprising bupropion in an effective amount and trazodone in an effective amount for improving SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, inducing weight loss, maintaining weight loss, and / or effectuating weight loss management, improving the subjective stateAttorney Docket No.49848-4040PCT or sense of well-being, self-esteem, and / or self-confidence, in treated subjects in need of such treatment.

[0191] The present invention is directed to novel and unique compositions comprising bupropion in an effective amount and trazodone in an effective amount for improving inducing weight loss, maintaining weight loss, and / or effectuating weight loss management, improving the subjective state or sense of well-being, self-esteem, and / or self-confidence, and increasing, enhancing and / or improving sexual desire and function in treated subjects in need of such treatment.

[0192] The present invention is directed to novel and unique compositions comprising bupropion in an effective amount and trazodone in an effective amount for inducing weight loss, maintaining weight loss, and / or effectuating weight loss management and increasing, enhancing and / or improving sexual desire, sexual fantasies and / or sexual function in treated subjects in need of such treatment.

[0193] The present invention is directed to novel and unique compositions comprising bupropion in an effective amount and trazodone in an effective amount for inducing weight loss, maintaining weight loss, and / or effectuating weight loss management, increasing, enhancing and / or improving sexual desire, sexual fantasies and / or sexual function and improving the subjective state of a state or sense of well-being, self-esteem, and / or self-confidence in treated subjects in need of such treatment.

[0194] Thus, the present inventors have now discovered a therapeutic strategy that addresses SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, and obesity, weight loss, and / or weight loss maintenance in a subject. The present inventors have also now discovered a therapeutic strategy that addresses obesity, weight loss, undesirable or unwanted weight, weight loss maintenance and one or more of the following SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE,Attorney Docket No.49848-4040PCT MDL, MDO, and the like, and low or poor or a lack of a subjective state or sense of well- being, self-esteem, and / or self-confidence in a subject.

[0195] The present invention relates, at least in part, to the discovery that a combination of a 5-HT2A antagonist (which is optionally a 5-HT1A receptor agonist), a norepinephrine-dopamine reuptake inhibitor, (and optionally an endocrine active agent) provides unexpected superior and synergistic results in addressing SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like obesity, weight loss, undesirable or unwanted weight, weight loss maintenance, and / or low or poor or a lack of a subjective state or sense of well-being, self-esteem, and / or self-confidence in a subject.

[0196] Broadly, the present invention relates, at least in part, to the discovery that the combination of a 5-HT2A antagonist (which is optionally a 5-HT1A receptor agonist), and norepinephrine-dopamine reuptake inhibitor, provides unexpected superior and synergistic results in addressing SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, obesity, weight loss, and / or effectuating weight loss maintenance.

[0197] Also broadly, the present invention relates, at least in part, to the discovery that the combination of a 5-HT2A antagonist (which is optionally a 5-HT1A receptor agonist), and norepinephrine-dopamine reuptake inhibitor, provides unexpected superior and synergistic results in addressing obesity, weight loss, undesirable or unwanted weight, and / or weight loss maintenance and one or more of the SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, and low or poor or a lack of a subjective state or sense of well- being, self-esteem, and / or self-confidence in a subject.

[0198] The present invention also provides novel and unique methods for treating subjects in need of treatment for obesity, weight loss, undesirable or unwanted weight, and / or weight loss maintenance, and one or more of the following SD, e.g., FSD, HSDD,Attorney Docket No.49848-4040PCT FSAD, FOD, FSIAD, FPD, SIAD, and / or MSD, including ED, PD, PE, MHSDD, MDE, MDL, MDO, and the like, and / or poor or low or a lack of a subjective state or sense of well-being, self-esteem, and / or self-confidence. 1. DEFINITIONS

[0199] Before further description of the present invention, and in order that the invention may be more readily understood, certain terms are first defined and collected here for convenience.

[0200] The singular forms “a,” and “an” mean one or more unless specifically indicated otherwise. Further, unless otherwise required by context, singular terms shall include pluralities, and plural terms shall include the singular.

[0201] Scientific or technical terms used in connection with the present application shall have meanings that are commonly understood by those of ordinary skill in the art, unless otherwise defined herein.

[0202] As used in this disclosure and in the claims, the open-ended transitional phrases “comprise(s),” “comprising,” “comprised of,” “include(s),” “including,” “included,” “having,” “contain(s),” “containing,” “contained,” and variants thereof require the presence of the specified elements, ingredients, components, items and / or steps, but the claims may also include or cover other, unspecified elements, ingredients, components, items and / or steps.

[0203] Also as used in this disclosure and in the claims, the close-ended transitional phrases “consist of,” “consists of,” or “consisting of,” indicate that the claims are closed and limited to the elements, ingredients, components, items and / or steps specifically recited in the claims, and that the claims are closed to and do not cover or include other unspecified elements, ingredients, components, items and / or steps.Attorney Docket No.49848-4040PCT

[0204] Also as used in this disclosure and in the claims, the semi-closed transitional phrases, such as “consist essentially of,” “consists essentially,” or “consisting essentially of” limit the scope of claims to the specified elements, ingredients, components, items and / or steps in the claims and to others that do not materially affect the basic and / or novel characteristics of the claims. In other words, the semi-closed transitional phrases serve as “in between” transitional phrases, i.e., transitional phrases between the open-ended transitional phrases and the closed-ended transitional phrases and indicate that the claims are limited to the specified elements, ingredients, components, items and / or steps in the claims, but also cover or include other unspecified elements, ingredients, components, items and / or steps that do not materially affect the basic and novel characteristic(s) of the claimed invention.

[0205] The use of the term “or” in this disclosure and claims is used to mean “and / or,” unless explicitly indicated to refer only to the disjunctive, that is, alternatives only or the alternatives are mutually exclusive. The use of the term “and” in this disclosure and claims is used to also mean “and / or,” unless explicitly indicated to refer only to the conjunctive, that is, an inclusive connection, addition, or joinder of items.

[0206] Numerical values in this disclosure and claims should be understood to include numerical values which are the same when reduced to the same number of significant figures and numerical values which differ from the stated value by less than the experimental error of conventional measurement technique of the type described in this disclosure to determine the value.

[0207] The terms “range(s),” as used herein are inclusive of the recited endpoints and independently combinable, for example, the range of “from 2 grams to 10 grams” is inclusive of the endpoints, 2 grams and 10 grams, and all the intermediate numerical gram values therebetween, as if each intermediate numerical gram value therebetween has been individually set forth herein.Attorney Docket No.49848-4040PCT

[0208] The term “about” can be used to include any numerical value that can vary without changing the basic function of that value. When used with a range, “about” also discloses the range defined by the absolute values of the two endpoints, e.g. “about 2 to about 4” also discloses the range “from 2 to 4 and any integer therebetween.” The term “about” may refer to ±1% of the indicated number or ±60 minutes of an indicated time. Other than in the operating examples, or where otherwise indicated, all numbers expressing quantities of ingredients or reaction conditions used herein should be understood as modified in all instances by the term "about." The term "about" when used in connection with percentages means ±1% of the percentage number.

[0209] The term “substantially” when used in this disclosure and claims to modify “a period of time,” it refers to about ±24 hours and any time occurring therebetween as if the intermediate time values have been individually stated, of the indicated time period being so modified. For example, “substantially together” or “substantially administered together” or “substantially co-administered together,” means items were given together at the same time or within ±24 hours of one another or anytime between 24 hours.

[0210] The term “substantially” when used in this disclosure and claims to modify a composition, it refers to a composition comprising at least 90% of the desired compound. The term “more substantially” is used to represent a composition comprising at least 95% of the desired compound. The term “essentially” is used to represent a composition comprising at least 97% of the desired compound. Conversely, the term “substantially free of” or “substantially free” in terms of a specified component, is used herein to mean that none of the specified component has been purposefully formulated into or is included in a composition or compound and / or is present only as a contaminant or in trace amounts. The total amount of all containments, by-products, and other material present in a composition or compound is in an amount less than 5%. The term “more substantially free of” or “more substantially free” is used to represent that a composition or compound contains less than 3% of a specific component. The term “essentially free of” or “essentially free” contains less than 2% of a specific component.Attorney Docket No.49848-4040PCT

[0211] The terms “patient(s),” “subject(s),” or “individual(s)” or “person(s) are used interchangeably herein and refer to either a human or a non-human animal. These terms include any mammals, such as humans, primates, livestock animals, including bovines, porcine, etc., companion or domesticated animals, e.g., canines, felines, etc., rodents and laboratory animals, e.g., mice, rats, dogs, rabbits, monkeys, and the like, and wild and zoo animals, e.g., lions, tigers, bears, elephants, giraffes, etc. In a typical embodiment, the subject or patient is a human, male and female. Thus, the term "subject" includes animals which are capable of suffering from a sexual disorder or who could otherwise benefit from the administration of a compound or composition of the invention, such as human (male or female) and non-human animals (male or female). Preferred humans include obese or overweight human patients. Other preferred humans include obese or overweight human patients suffering from or prone to suffering from hypoactive sexual desire disorder or associated state or other sexual disorders or disease, as described herein.

[0212] A "Responder", as used herein, means a sexual desire Responder, one who improves by 2 points on the standard scale from 2-10. Responder is defined on the desire subscale of the Female Sexual Function Inventory; the subscale ranges from 2 (desire at very low or none and almost never or never) to 10 (desire at very high and almost always or always).

[0213] A "Remitter", as used herein is one whose score is at least 5.

[0214] Alternatively, a sexual distress Responder is one who improves by one point on the standard scale from 0 to 4. The measure is the "bothered by low sexual desire" item of the Female Sexual Distress Scale - Revised, and it ranges from 4, always, to 0, never, and a Remitter is one whose score is no higher than 2, occasionally.

[0215] The terms “administering” or “administration of” or “administered” or “administers,” as used herein, are used interchangeably and relate to administering a substance, a compound, a pharmaceutical composition, product, agent, or medicalAttorney Docket No.49848-4040PCT treatment to a patient to perform their intended function and that can be carried out using one of a variety of methods known to those skilled in the art. The terms therefore include routes of introducing the compounds or compositions of the present invention to a subject to perform their intended function and carry out the objectives of the present invention. For example, a substance, compound, composition, product, agent, including the combination of the present invention, or medical treatment can be administered intravenously, arterially, intradermally, intramuscularly, intraperitoneally, subcutaneously, ocularly, sublingually, orally (by ingestion), intranasally, including by inhalation, intraspinal, intracerebral, and transdermal by absorption, e.g., through a skin duct. A substance, compound, composition, product, agent, including the combinations of the present invention, or medical treatment can also appropriately be introduced by rechargeable or biodegradable polymeric devices or other devices, e.g., patches and pumps, or formulations, which provide for the extended, slow, modified or controlled, sustained or delayed release of the substance, compound or agent. Administration can also be performed, for example, once, a plurality of times, and / or over one or more extended periods. Thus, the pharmaceutical preparations of the [present invention may be given by forms suitable for each administration route. For example, these preparations are administered in tablet, caplet or capsule form, by injection, inhalation, eye lotion, ointment, suppository, etc. administration by injection, infusion or inhalation; topical by lotion or ointment; and rectal by suppositories. Oral administration is preferred. The injection can be bolus, auto-injected or self -injected, or can be continuous infusion. Depending on the route of administration, the compound of the invention can be coated with or disposed of in a selected material to protect it from natural conditions which may detrimentally affect its ability to perform its intended function. The compounds of the present invention can be administered alone, or in conjunction with either another agent as described above or with a pharmaceutically acceptable carrier, or both. The compounds of the present invention can be administered prior to the administration of the other agent, simultaneously with the agent, or after the administration of the agent. Furthermore, the compounds of the present invention can also be administered in a pro- drug form which is converted into its active metabolite, or more active metabolite in vivo.Attorney Docket No.49848-4040PCT

[0216] The terms “co-administration,” “co-administering,” “co-administers,” co- administered, and the like, as used herein, refers to the act of administering or giving or taking two or more drugs or medical treatments together at a certain time, such as either (a) at the same or identical time, (b) at about the same time, (c) at substantially the same time, (d) at different times of the day, or (e) on different days of the week, month or year, depending upon the treatment regimen, dosage form and dosage strength of each drug being co-administered. The term “route(s) of medication” and these above terms in this ¶222 refer to the route by which each drug or medical treatment is administered, given or taken, such as enteral, oral, sublingual, buccal, rectal, parenteral, intravenous, intramuscular, subcutaneous, topical, nasal and / or inhalation routes of medication and as described herein. The pharmaceutical preparations may be given by forms suitable for each administration route. For example, these preparations are administered in tablet, caplet, capsule, or powder form, by injection, inhalation, eye lotion, ointment or drops, suppository, ointment. cream, lotion, etc. administration by injection, infusion or inhalation; topical by lotion or ointment; and rectal by suppositories. Oral administration is preferred.

[0217] An "effective amount" is generally an amount sufficient to reduce the severity and / or frequency of symptoms, eliminate the symptoms and / or underlying cause, prevent the occurrence of symptoms and / or their underlying cause, and / or improve or remediate the damage that results from or is associated with the disease state, e.g., diabetes, obesity, dyslipidemia, elevated glucose levels, elevated insulin levels or diabetic nephropathy. Thus, term "effective amount" includes an amount effective, at dosages and for periods of time necessary, to achieve the desired result, e.g., sufficient to treat a hypoactive sexual desire disorder in a subject, and / or the ability of the compound to elicit a desired response in a subject. In other words, the term "effective amount," means an amount sufficient to remedy or improve a disease state, disorder, dysfunction, condition or a symptom, particularly a condition or symptoms associated with obesity, overweightness, undesirable or unwanted weight, weight maintenance, low or poor or a lack of a subjective state or sense of well-being, self-esteem, and / or self-confidence, sexual desire, sexual dysfunction and the like, or otherwise prevent, hinder, retard or reverse the progression of a disease state, disorder, dysfunction, condition, or symptomAttorney Docket No.49848-4040PCT or any other undesirable symptom associated with the disease, disorder or dysfunction in any way whatsoever. An effective amount of a compound of the present invention may therefore vary according to factors such as the disease state, disorder or dysfunction, age, and weight of the subject, and the ability of the compound of the invention to elicit a desired response in the subject. Dosage regimens may be adjusted to provide the optimum therapeutic response. An effective amount is also one in which any toxic or detrimental effects, e.g., side effects, of the compounds of the present invention are outweighed by therapeutically beneficial effects.

[0218] A “therapeutically effective amount” of compound of the invention, i.e., an effective dosage) may range from about 0.001 to about 30 mg / kg body weight, preferably about 0.01 to about 25 mg / kg body weight, more preferably about 0.1 to about 20 mg / kg body weight, and even more preferably about 1 to about 10 mg / kg, about 2 to about 9 mg / kg, about 3 to about 8 mg / kg, about 4 to about 7 mg / kg, or about 5 to about 6 mg / kg body weight. The skilled artisan will appreciate that certain factors may influence the dosage required to effectively treat a subject, including but not limited to the severity of the disease or disorder, previous treatments, the general health and / or age of the subject, and other diseases present. Moreover, treatment of a subject with a therapeutically effective amount of a compound of the invention can include a single treatment, acute treatment or chronic treatment, or, preferably, can include a series of treatments. In one example, a subject is treated with a compound of the invention in the range of between about 0.1 to about 20 mg / kg body weight, one time per week for between about 1 to about 52 weeks or more, preferably between about 2 to about 8 weeks, more preferably between about 3 to about 7 weeks, and even more preferably for about 4, about 5, or about 6 weeks. In other words, treatments can be for as long as necessary to accomplish the treated objective and then for as long as necessary to maintain the achieved objective. It will also be appreciated that the effective dosage of a compound of the invention used for treatment may increase or decrease over the course of a particular treatment. Administration regimens herein where designated are in accordance with the following abbreviations: SID or QD or qd=Once a day; BID=Twice a day, TID=Three times a day; QID=Four times a day; q.h.s=every night. A "therapeutically effective amount" of aAttorney Docket No.49848-4040PCT compound of the present invention also refers to an amount of an agent which is effective, upon single, multiple, acute or chronic dose administration to an obese or overweight patient or a patient wanting to lose undesirable or unwanted weight, in modulating the patient’s obesity or the patient’s weight, as well as SD and / or low or poor or a lack of a subjective state or sense of well-being, self-esteem, and / or self-confidence, and / or symptoms of a SD and / or low or poor or a lack of a subjective state or sense of well- being, self-esteem, and / or self-confidence from which the patient may suffer, or in improving the patient, either objectively or subjectively according to the patient or health care provider, beyond that expected in the absence of such treatment.

[0219] The language "a prophylactically effective amount" of a compound refers to an amount of a compound of the invention any formula herein or otherwise described herein which is effective, upon single or multiple dose administration to the patient, in preventing or treating a sexual disorder or dysfunction.

[0220] The language "reduced toxicity" is intended to include a reduction in any undesired side effect elicited by a compound of the invention when administered in vivo.

[0221] The language “treatment limiting toxicity,” or “treatment limiting side effect(s),” as used herein refers to side effects of a drug or other treatment that are serious enough or severe to the treatment needs to be discontinued.

[0222] The language “dose limiting,” as used herein refers to side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment.

[0223] The terms "treating,” “treatment," ‘treats,” “treated,” and the like refers to any indicia of success in the treatment or amelioration of an injury, pathology, disease, disorder, condition or symptom, including any objective or subjective parameter such as abatement, remission, diminishing of symptoms or making the injury, pathology, disease, disorder, symptom or condition more tolerable to the patient, slowing in the rate ofAttorney Docket No.49848-4040PCT degeneration or decline, making the final point of degeneration less debilitating; improving a patient's physical or mental well-being. The treatment or amelioration of symptoms can be based on objective or subjective parameters, including the results of a physical examination, weight measurement, neuropsychiatric exams, questionnaires, screening, and / or a psychiatric evaluation. Thus, the term “treat” is used to refer to a reduction in progression of a disease, disorder, symptom or condition, a regression in a disease, disorder, symptom or condition, and / or a prophylactic usage to reduce the probability of presentation of a disease, disorder, symptom, or condition consistent with as defined herein above. This can be measured, for example, in several different ways. Certain methods presented herein successfully treat obesity by inducing weight loss in the patient thereby ameliorating symptoms associated with the patient being obese. Other methods presented herein successfully treat HSDD by increasing a patient’s sexual desire, sexual fantasies, and sexual function, and / or causing remission of a patients’ lack of sexual desire, lack of sexual fantasies and sexual dysfunction, and / or ameliorating symptoms associated with HSDD. Further methods presented herein successfully treat a patient’s low or poor or a lack of a subjective state or sense of well-being, self-esteem, and / or self- confidence by improving the patient’s subjective state or sense of well-being, self- esteem, and / or self-confidence, anhedonia, fatigue, motivation, emotions, and focus and / or to continue to ameliorate symptoms or conditions associated with a patient’s low or poor subjective well-being and / or self-esteem, and / or negative emotions. Still other methods presented herein successfully treat body weight and successfully effectuate body weight maintenance of a patient by inducing weight loss in the patient thereby ameliorating symptoms associated with the patient being overweight, and / or maintaining patient weight loss or maintaining a certain weight at which the patient wants maintained or has been prescribed to be maintained, and / or to continue to ameliorate symptoms or conditions associated with a patient being overweight.

[0224] The terms “preventing,” “prevents” or “prevent” or “prevented” are art- recognized, and when used in relation to diseases, disorders, symptoms or conditions relating to obesity, overweightness, undesirable or unwanted weight, weight issues, weight maintenance, weight management, SD and / or low or poor or a lack of a subjectiveAttorney Docket No.49848-4040PCT state or sense of well-being, self-esteem, and / or self-confidence in a subject are well understood in the art, and includes administration or co-administration of a drug, compound, product, composition, pharmaceutical composition, or agent which reduces the frequency of, or delays the onset of, the disease, disorder, symptom or condition in a subject relative to a subject which does not receive the drug, compound, product, composition, pharmaceutical composition, or agent.

[0225] The term "susceptible to SD,” such as FSD, HSDD, FSAD, FOD, FSIAD, and / or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, is meant to include subjects at risk of developing a SD, such as FSD, HSDD, FSAD, FOD, FSIAD, and / or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, e.g., subjects previously diagnosed as having or having a family or medical history of a SD, such as FSD, HSDD, FSAD, FOD, FSIAD, and / or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like.

[0226] The phrases "systemic administration, "administered systemically", "peripheral administration" and "administered peripherally" as used herein mean the administration of a compound of the invention(s), drug or other material, such that it enters the patient's system and, thus, is subject to metabolism and other like processes, for example, subcutaneous administration.

[0227] The term ''compound(s)'' is used herein to refer to a molecular entity, and ''compounds'' may thus have different structural elements besides the minimum element defined for each compound or group of compounds. The term ''compound(s)'' is also meant to cover pharmaceutically relevant forms hereof, i.e., a compound as defined herein or a pharmaceutically acceptable salt, amide, ester, solvate and the like thereof. Compounds may display extended half-lives gained by substituent addition. A compound may be a drug and / or an API.Attorney Docket No.49848-4040PCT

[0228] The term “dosage form,” as used herein means the physical form in which a drug is produced and dispensed, such as a solid, liquid, topical, injectable, intranasal, otic, ophthalmic, inhalant, and suppository dosage forms, like a tablet, capsule, caplet, pill, powder, troche, liquid, syrup, emulsion, suspension, cream, ointment, gel, lotion, salve, film, patch, injectable and inhalant, See, for example, Drugs@FDA Glossary of Terms, FDA, available online at https: / / www.fda.gov / drugs / drug-approvals-and- databases / drugsfda-glossary-as a use the diagnosis, cure, mitigation, treatment, or prevention of disease or that can relieve symptoms of a disease, dysfunction or abnormal condition. More generally, the term “drug” can also mean (1) a substance recognized by an official pharmacopoeia or formulary, (2) a substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, (3) a substance (other than food) intended to affect the structure or any function of the body, (4) a substance intended for use as a component of a medicine but not a device or a component, part or accessory of a device. See, for example, Drugs@FDA Glossary of Terms, FDA, available online at https: / / www.fda.gov / drugs / drug-approvals-and-databases / drugsfda-glossary-

[0230] The term “drug product,” as used herein refers to the finished dosage form that contains a drug, generally, but not necessarily in association with other active or inactive ingredients. See, for example, Drugs@FDA Glossary of Terms, FDA, available online at https: / / www.fda.gov / drugs / drug-approvals-and-databases / drugsfda-glossary- terms#:~:text=A%20substance%20intended%20for%20use,treatment%2C%20or%20prAttorney Docket No.49848-4040PCT

[0231] A “pharmaceutical composition,” as used herein, means a mixture of substances suitable for administering to an individual that includes a pharmaceutical drug, an active pharmaceutical ingredient, or a compound. Generally, they are made of a combination of active pharmaceutical and inactive ingredients to control dosage delivery, enhance performance and appearance, help with absorption, facilitate manufacture and more. Active pharmaceutical ingredient(s), (“API(s),” provide the therapeutic effects of pharmaceutical compositions. Inactive ingredients are also called excipients. A pharmaceutical composition may comprise a combination of the present invention and a sterile aqueous solution.

[0232] As contemplated herein, an “API” can be a “drug” or a “compound,” a “drug” can be an “API” or a “compound,” and a “compound” can be an “API” or a “drug.” Thus, the terms as used herein can mean individually, collectively or interchangeably.

[0233] The term “combination,” as used herein means bupropion or a pharmaceutically acceptable salt, amide, ester, solvate and the like thereof and trazodone or a pharmaceutically acceptable salt, amide, ester, solvate and the like thereof, and the terms API(s), drug and compound include but may not necessarily be limited to the “combination.”

[0234] As contemplated herein, a “dosage form” can be a “drug product” or a “pharmaceutical composition,” a “drug product” can be a “dosage form” or a “pharmaceutical composition,” and a pharmaceutical composition” can be a “dosage form” or a “drug product,” Thus, such terms as used herein can be mean individually, collectively or interchangeably herein.

[0235] The term “drug release,” as contemplated herein, includes various forms of drug release products as defined by the FDA which includes “immediate release” drug products, “modified release” drug products, “delayed release” drug products, and “extended release’ drug products. See, e.g., Controlling Drug Delivery, Chapter 1, Pharmaceutics: Drug Delivery and Targeting, Edited by Yvonne Perrie and ThomasAttorney Docket No.49848-4040PCT Rades, Second Edition, Pharmaceutical Press, June 1, 2012, ISBN9780857110596, available online at https: / / web.archive.org / web / 20220428170202 / http: / / www.pharmpress.com / files / docs / ft_ and atcontents for absorption without delay. In other words, “immediate release” drug products release drugs immediately after administration. See Controlling Drug Delivery, supra.

[0237] By “modified release,” it refers to drug products wherein the drug release is delayed after its initial administration, i.e., a delayed release drug product, which can be for a prolonged period of time, e.g., an extended release “ER” drug product, “XR” drug product, or an “XL” drug product, or which can be released to a specific target in the body, e.g., a “targeted-release” drug product. In other words, ‘modified release” drug products refer to drug products wherein drug release only occurs sometime after administration or for a prolonged period of time or to a specific target in the body. Modified release drug products can provide therapeutic, or convenience objectives not offered by conventional dosage forms such as drug product solutions or immediate-release dosage drug products. “Modified release” solid oral dosage forms or drug products include both “delayed release” drug products and “extended release” drug products. See Controlling Drug Delivery, supra.

[0238] By “delayed release,” it refers to drug products that release drugs only at some point following initial oral administration of the drug product. See Controlling Drug Delivery, supra.

[0239] By “extended release,” it refers to drug products that release drugs over extended periods of time after initial oral administration. Because “extended release” drug products prolong drug release, they allow for a reduction in dosing frequency thatAttorney Docket No.49848-4040PCT may offer dosing and / or therapeutic conveniences over conventional drug products, such as solution drug products or immediate-release drug products. Extended release drug products include sustained release (“SR”) drug products or controlled release (“CR”) drug products. See Controlling Drug Delivery, supra.

[0240] By “sustained release,” it refers to drug products that maintain the rate of drug release over a sustained period of time but not necessarily at a constant rate. In other words, “sustained release” drug products release drugs at a designed rate to maintain constant drug concentration for a selected period of time to maintain efficacy and reduced side effects. See Controlling Drug Delivery, supra

[0241] By “controlled release,” it refers to drug products that maintain drug release over a sustained period but at a somewhat constant rate. Thus, “extended release” can be achieved using “release” or “controlled release” drug products. See Controlling Drug Delivery, supra. The term “controlled release” of “CR,” is used herein in its ordinary sense and thus includes pharmaceutical compositions that may be combined or coated with ingredients, such as, rate controlling agents, to alter their dissolution profiles.

[0242] The terms “modified release,” “extended release,” “delayed release,” sustained release,” and “controlled release,” maybe used interchangeably herein. Thus, the term “sustained release,” or “SR,” or “extended release” or “ER,” or modified release,” of “MR,” as used herein refers to a pharmaceutical composition which is a type of a controlled release formulation wherein the dissolution profile is extended over a longer period of time than that of an immediate release formulation comprising a similar pharmaceutical composition. In other words, these medications prolong the medication’s release from a tablet, caplet or capsule so that the benefits of these medication are received over a longer period of time, which means the medications can be taken less frequently or in fewer doses throughout the day.Attorney Docket No.49848-4040PCT

[0243] However, it is to be understood that the term “modified release” is used broadly herein and is intended to include all forms of modified release, such as “extended release,” “delayed release,” sustained release,” and “controlled release.”

[0244] As generally used herein "pharmaceutically acceptable" refers to those compounds, materials, ingredients, elements, compositions, compositions containing such compounds and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in patients, including in contact with the tissues, organs, and / or bodily fluids of human beings and animals without excessive toxicity, irritation, allergic response, or other problems or complications commensurate with a reasonable benefit / risk ratio. The term “pharmaceutically acceptable” includes pharmaceutically acceptable salts, amides, esters and the like.

[0245] The term "pharmaceutically acceptable carrier,” as used herein includes pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material, involved in carrying or transporting the subject chemical from one organ, or portion of the body, to another organ, or portion of the body. Each carrier is "acceptable" in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient. Some examples of materials which can serve as pharmaceutically-acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol; (20) phosphate buffer solutions; and (21) other non-toxic compatible substances employed in pharmaceutical formulations.Attorney Docket No.49848-4040PCT

[0246] “Pharmaceutical excipient(s),” as used herein, are ingredients other than the active pharmaceutical ingredient (API) present in a finished pharmaceutical composition. These are frequently used as lubricants, diluents, carriers, binders, solubilizers, emulsifiers, stabilizers, preservatives, flavorings, coating agents, and coloring agents for formulation.

[0247] ''Pharmaceutically acceptable salt(s)'' are non-toxic salts at the concentration at which they are administered. Thus, pharmaceutically acceptable salt(s) refers to a formulation of a compound complexed with a salt that does not cause significant irritation to a subject to which it is administered and does not negate the biological activity and properties of the compound. Pharmaceutically acceptable salts include acid addition salts such as those containing sulfate, hydrochloride, phosphate, sulfamate, acetate, citrate, lactate, tartrate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, cyclohexylsulfamate and quinate. Pharmaceutically acceptable salts can be obtained from acids such as hydrochloric acid, sulfuric acid, phosphoric acid, sulfamic acid, acetic acid, citric acid, lactic acid, tartaric acid, malonic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p- toluenesulfonic acid, cyclohexylsulfamic acid, and quinic acid. Such salts may be prepared by, for example, reacting the free acid or base forms of the product with one or more equivalents of the appropriate base or acid in a solvent or medium in which the salt is insoluble, or in a solvent such as water which is then removed in vacuo or by freeze- drying or by exchanging the ions of an existing salt for another ion on a suitable ion exchange resin.

[0248] The term "alkyl" refers to the radical of saturated aliphatic groups, including straight-chain alkyl groups, branched-chain alkyl groups, cycloalkyl (alicyclic) groups, alkyl substituted cycloalkyl groups, and cycloalkyl substituted alkyl groups. The term alkyl further includes alkyl groups, which can further include oxygen, nitrogen, sulfur or phosphorous atoms replacing one or more carbons of the hydrocarbon backbone, e.g., oxygen, nitrogen, sulfur or phosphorous atoms. In preferred embodiments, a straightAttorney Docket No.49848-4040PCT chain or branched chain alkyl has 30 or fewer carbon atoms in its backbone (e.g., C1-C30 for straight chain, C3-C30 for branched chain), preferably 26 or fewer, and more preferably 20 or fewer, and still more preferably 4 or fewer. Likewise, preferred cycloalkyls have from 3-10 carbon atoms in their ring structure, and more preferably have 3, 4, 5, 6 or 7 carbons in the ring structure.

[0249] Moreover, the term alkyl as used throughout the specification and sentences is intended to include both "unsubstituted alkyls" and "substituted alkyls," the latter of which refers to alkyl moieties having substituents replacing a hydrogen on one or more carbons of the hydrocarbon backbone. Such substituents can include, for example, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinato, cyano, amino (including alkyl amino, dialkylamino, acylamino, diarylamino, and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkylaryl, or an aromatic or heteroaromatic moiety. It will be understood by those skilled in the art that the moieties substituted on the hydrocarbon chain can themselves be substituted, if appropriate. Cycloalkyls can be further substituted, e.g., with the substituents described above. An "alkylaryl" moiety is an alkyl substituted with an aryl (e.g., phenylmethyl (benzyl)). The term "alkyl" also includes unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but that contain at least one double or triple bond respectively.

[0250] Unless the number of carbons is otherwise specified, "lower alkyl" as used herein means an alkyl group, as defined above, but having from one to ten carbons, more preferably from one to six, and still more preferably from one to four carbon atoms in its backbone structure, which may be straight or branched-chain. Examples of lower alkyl groups include methyl, ethyl, n-propyl, i-propyl, tert-butyl, hexyl, heptyl, octyl and so forth.Attorney Docket No.49848-4040PCT In preferred embodiment, the term "lower alkyl" includes a straight chain alkyl having 4 or fewer carbon atoms in its backbone, e.g., C1-C4 alkyl.

[0251] The terms "alkoxyalkyl," "polyaminoalkyl" and "thioalkoxyalkyl" refer to alkyl groups, as described above, which further include oxygen, nitrogen or sulfur atoms replacing one or more carbons of the hydrocarbon backbone, e.g., oxygen, nitrogen or sulfur atoms.

[0252] The terms "alkenyl" and "alkynyl" refer to unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but that contain at least one double or triple bond, respectively. For example, the invention contemplates cyano and propargyl groups.

[0253] The term "aryl" as used herein, refers to the radical of aryl groups, including 5- and 6-membered single-ring aromatic groups that may include from zero to four heteroatoms, for example, benzene, pyrrole, furan, thiophene, imidazole, benzoxazole, benzothiazole, triazole, tetrazole, pyrazole, pyridine, pyrazine, pyridazine and pyrimidine, and the like. Aryl groups also include polycyclic fused aromatic groups such as naphthyl, quinolyl, indolyl, and the like. Those aryl groups having heteroatoms in the ring structure may also be referred to as "aryl heterocycles," "heteroaryls" or "heteroaromatics." The aromatic ring can be substituted at one or more ring positions with such substituents as described above, as for example, halogen, hydroxyl, alkoxy, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl, phosphate, phosphonato, phosphinato, cyano, amino (including alkyl amino, dialkylamino, arylamino, diarylamino, and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, imino, sulfhydryl, alkylthio, aiylthio, thiocarboxylate, sulfates, sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkylaryl, or an aromatic or heteroaromatic moiety. Aryl groups can also be fused or bridged with alicyclic or heterocyclic rings which are not aromatic so as to form a polycycle (e.g., tetralin).Attorney Docket No.49848-4040PCT

[0254] The term "associating with" refers to a condition of proximity between a chemical entity or compound, or portions thereof, and a binding pocket or binding site on a protein. The association may be non-covalent (wherein the juxtaposition is energetically favored by hydrogen bonding or van der Waals or electrostatic interactions) or it may be covalent.

[0255] The language "biological activities" of a compound of the invention includes all activities elicited by compound of the inventions in a responsive cell. It includes genomic and non-genomic activities elicited by these compounds.

[0256] "Biological composition" or "biological sample" refers to a composition containing or derived from cells or biopolymers. Cell-containing compositions include, for example, mammalian blood, red cell concentrates, platelet concentrates, leukocyte concentrates, blood cell proteins, blood plasma, platelet-rich plasma, a plasma concentrate, a precipitate from any fractionation of the plasma, a supernatant from any fractionation of the plasma, blood plasma protein fractions, purified or partially purified blood proteins or other components, serum, semen, mammalian colostrum, milk, saliva, placental extracts, a cryoprecipitate, a cryosupernatant, a cell lysate, mammalian cell culture or culture medium, products of fermentation, ascites fluid, proteins induced in blood cells, and products produced in cell culture by normal or transformed cells (e.g., via recombinant DNA or monoclonal antibody technology). Biological compositions can be cell-free. In a preferred embodiment, a suitable biological composition or biological sample is a red blood cell suspension. In some embodiments, the blood cell suspension includes mammalian blood cells. Preferably, blood cells are obtained from a human, a non-human primate, a dog, a cat, a horse, a cow, a goat, a sheep or a pig. In preferred embodiments, the blood cell suspension includes red blood cells and / or platelets and / or leukocytes and / or bone marrow cells.Attorney Docket No.49848-4040PCT

[0257] The term "chiral" refers to molecules which have the property of non- superimposability of the mirror image partner, while the term "achiral" refers to molecules which are superimposable on their mirror image partner.

[0258] The term "diastereomers" refers to stereoisomers with two or more centers of dissymmetry and whose molecules are not mirror images of one another.

[0259] The term "enantiomers" refers to two stereoisomers of a compound which are non-superimposable mirror images of one another. An equimolar mixture of two enantiomers is called a "racemic mixture" or a "racemate." The compounds of this invention may contain one or more asymmetric centers and thus occur as racemates and racemic mixtures, single enantiomers, individual diastereomers and diastereomeric mixtures. All such isomeric forms of these compounds are expressly included in the present invention. The compounds of this invention may also be represented in multiple tautomeric forms, in such instances, the invention expressly includes all tautomeric forms of the compounds described herein. All such isomeric forms of such compounds are expressly included in the present invention. All crystal forms of the compounds described herein are expressly included in the present invention.

[0260] The term "enantiomers" refers to two stereoisomers of a compound which are non-superimposable mirror images of one another. An equimolar mixture of two enantiomers is called a "racemic mixture" or a "racemate." The compounds of this invention may contain one or more asymmetric centers and thus occur as racemates and racemic mixtures, single enantiomers, individual diastereomers and diastereomeric mixtures. All such isomeric forms of these compounds are expressly included in the present invention. The compounds of this invention may also be represented in multiple tautomeric forms, in such instances, the invention expressly includes all tautomeric forms of the compounds described herein. All such isomeric forms of such compounds are expressly included in the present invention. All crystal forms of the compounds described herein are expressly included in the present invention.Attorney Docket No.49848-4040PCT

[0261] The term "haloalkyl" is intended to include alkyl groups as defined above that are mono-, di- or polysubstituted by halogen, e.g., fluoromethyl and trifluoromethyl.

[0262] The term "halogen" designates --F, --Cl, --Br or --I.

[0263] The term "hydroxyl" means --OH.

[0264] The term "heteroatom" as used herein means an atom of any element other than carbon or hydrogen. Preferred heteroatoms are nitrogen, oxygen, sulfur and phosphorus.

[0265] The term "homeostasis" is art-recognized to mean maintenance of static, or constant, conditions in an internal environment.

[0266] The language "improved biological properties" refers to any activity inherent in a compound of the invention that enhances its effectiveness in vivo. In a preferred embodiment, this term refers to any qualitative or quantitative improved therapeutic property of a compound of the invention, such as reduced toxicity.

[0267] The term "optionally substituted" is intended to encompass groups that are unsubstituted or are substituted by other than hydrogen at one or more available positions, typically 1, 2, 3, 4 or 5 positions, by one or more suitable groups (which may be the same or different). Such optional substituents include, for example, hydroxy, halogen, cyano, nitro, C1-C8alkyl, C2-C8 alkenyl, C2-C8alkynyl, C1-C8alkoxy, C2-C8alkyl ether, C3- C8alkanone, C1-C8alkylthio, amino, mono- or di-(C1-C8alkyl)amino, haloC1-C8alkyl, haloC1-C8alkoxy, C1-C8alkanoyl, C2-C8alkanoyloxy, C1-C8alkoxycarbonyl, --COOH, --CONH2, mono- or di-(C1- C8alkyl)aminocarbonyl, --SO2NH2, and / or mono or di(C1-C8alkyl)sulfonamido, as well as carbocyclic and heterocyclic groups. Optional substitution is also indicated by the phrase "substituted with from 0 to X substituents," where X is the maximum number of possible substituents. Certain optionally substituted groups are substituted with from 0 to 2, 3 or 4Attorney Docket No.49848-4040PCT independently selected substituents (i.e., are unsubstituted or substituted with up to the recited maximum number of substituents).

[0268] The term "isomers" or "stereoisomers" refers to compounds which have identical chemical constitution but differ with regard to the arrangement of the atoms or groups in space.

[0269] The term "modulate" refers to an increase or decrease, e.g., the alteration in hypoactive sexual desire disorder and / or symptoms thereof in a subject such that a desired end result is achieved, e.g., a therapeutic result.

[0270] The term "obtaining" as in "obtaining a compound useful in treating hypoactive sexual desire disorder" is intended to include purchasing, synthesizing or otherwise acquiring the compound.

[0271] The phrases "parenteral administration" and "administered parenterally" as used herein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticulare, subcapsular, subarachnoid, intraspinal and intrasternal injection and infusion.

[0272] The terms "polycyclyl" or "polycyclic radical" refer to the radical of two or more cyclic rings (e.g., cycloalkyls, cycloalkenyls, cycloalkynyls, aryls and / or heterocyclyls) in which two or more carbons are common to two adjoining rings, e.g., the rings are "fused rings". Rings that are joined through non-adjacent atoms are termed "bridged" rings. Each of the rings of the polycycle can be substituted with such substituents as described above, as for example, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinato, cyano, amino (including alkylamino, dialkylamino, arylamino, diarylamino,Attorney Docket No.49848-4040PCT and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkyl, alkylaryl, or an aromatic or heteroaromatic moiety.

[0273] The term "prodrug" or "pro-drug" includes compounds with moieties that can be metabolized in vivo. Generally, the prodrugs are metabolized in vivo by esterases or by other mechanisms to active drugs. Examples of prodrugs and their uses are well known in the art (See, e.g., Berge et al. (1977) "Pharmaceutical Salts", J. Pharm. Sci. 66:1-19). The prodrugs can be prepared in situ during the final isolation and purification of the compounds, or by separately reacting the purified compound in its free acid form or hydroxyl with a suitable esterifying agent. Hydroxyl groups can be converted into esters via treatment with a carboxylic acid. Examples of prodrug moieties include substituted and unsubstituted, branch or unbranched lower alkyl ester moieties, (e.g., propionoic acid esters), lower alkenyl esters, di-lower alkyl-amino lower-alkyl esters (e.g., dimethylaminoethyl ester), acylamino lower alkyl esters (e.g., acetyloxymethyl ester), acyloxy lower alkyl esters (e.g., pivaloyloxymethyl ester), aryl esters (phenyl ester), aryl- lower alkyl esters (e.g., benzyl ester), substituted (e.g., with methyl, halo, or methoxy substituents) aryl and aryl-lower alkyl esters, amides, lower-alkyl amides, di-lower alkyl amides, and hydroxy amides. Preferred prodrug moieties are propionoic acid esters and acyl esters. Prodrugs which are converted to active forms through other mechanisms in vivo are also included.

[0274] The language "a prophylactically effective amount" of a compound refers to an amount of a compound of the invention any formula herein or otherwise described herein which is effective, upon single or multiple dose administration to the patient, in preventing or treating a sexual disorder.

[0275] The language "reduced toxicity" is intended to include a reduction in any undesired side effect elicited by a compound of the invention when administered in vivo.Attorney Docket No.49848-4040PCT

[0276] The term "susceptible to a hypoactive sexual desire disorder" is meant to include subjects at risk of developing hypoactive sexual desire disorder, e.g., subjects previously diagnosed as having or having a family or medical history of hypoactive sexual desire disorder, and the like.

[0277] The phrases "systemic administration, "administered systemically", "peripheral administration" and "administered peripherally" as used herein mean the administration of a compound of the invention(s), drug or other material, such that it enters the patient's system and, thus, is subject to metabolism and other like processes, for example, subcutaneous administration.

[0278] With respect to the nomenclature of a chiral center, terms "d" and "l" configuration are as defined by the IUPAC Recommendations. As to the use of the terms, diastereomer, racemate, epimer and enantiomer will be used in their normal context to describe the stereochemistry of preparations.

[0279] Thus, the pharmaceutical compositions of the present invention may be formulated, so as to release their contents after a time lag, or a little at a time, or in some other predetermined way and are referred to as “time-release” formulations, that include controlled release, sustained release, extended release and modified release pharmaceutical compositions. Many pharmaceutical compositions are time-release formulated to reduce their drugs local adverse effects in the gastrointestinal tract, to reduce adverse effects associated with the drugs peak blood levels, or to artificially extend the half-life of the drugs. Time-release formulations are associated with the added advantages of convenience of dosing, improved compliance, and less fluctuation in blood levels across the course of the day.

[0280] The definitions provided herein supersede any conflicting definition in any reference that is incorporated by reference herein or used in the art. The fact that certain terms are defined, however, should not be considered as indicative that any term that is undefined is indefinite. Rather, all terms used are believed to describe the disclosure inAttorney Docket No.49848-4040PCT terms of definiteness and enablement and such that one of ordinary skill can appreciate the scope and practice the present disclosure.

[0281] The terms “bupropion” and “trazodone” denote any pharmaceutical acceptable salts of bupropion and any pharmaceutical acceptable salts trazodone. Within the meaning of the present invention, and in one embodiment, the term “bupropion” preferably refers to the active pharmaceutical ingredient “bupropion hydrochloride”. Within the meaning of the present invention, and in another embodiment, the term “trazodone” preferably refers to the active pharmaceutical ingredient “trazodone hydrochloride”. Within the context of the present specification, both bupropion and trazodone or their pharmaceutical salts are sometimes commonly referred to as “drugs”.

[0282] A preferable effective amount of bupropion for treating subjects who are not obese ranges from about 326 mg to about 334 mg, and more preferably about 329.5 mg. A preferable effective amount of trazodone for treating subjects who are not obese ranges from about 124 mg to about 132 mg, and more preferably about 128.5 mg.

[0283] In other words, pharmaceutical compositions of the present invention comprise bupropion or pharmaceutically acceptable salt thereof in a dose range of about 326 mg to about 334 mg, and trazodone or pharmaceutically acceptable salt thereof in a dose range of about 124 mg to about 132 mg.

[0284] The present invention also contemplates a pharmaceutical composition comprising bupropion or a pharmaceutically acceptable salt thereof in a dose amount of about 329.5 mg and trazodone or pharmaceutically acceptable salt thereof in a dose range amount of about 128.5 mg.

[0285] A preferable effective amount of bupropion for treating subjects who are obese, a body mass of 30 kg / m2or greater, ranges from about 366 to about 374 mg, and more preferably about 369.5 mg. A preferable effective amount of trazodone for treating subjects who are not obese, including those with a body mass under 30 kg / m2, includingAttorney Docket No.49848-4040PCT overweight subjects with a body mass of 27 kg / m2or greater, ranges from about 139 to about 147 mg, and more preferably about 143.5 mg.

[0286] In other words, pharmaceutical compositions of the present invention comprise bupropion or pharmaceutically acceptable salt thereof in a dose range of about 366 mg to about 374 mg, and trazodone or pharmaceutically acceptable salt thereof in a dose range of about 139 mg to about 143.5 mg.

[0287] The present invention also contemplates a pharmaceutical composition comprised of bupropion or a pharmaceutically acceptable salt thereof in a dose amount of about 369.5 mg and trazodone or pharmaceutically acceptable salt thereof in a dose range amount of about 143.5 mg.

[0288] Nevertheless, an effective amount of bupropion or a pharmaceutically acceptable salt thereof and an effective amount of trazodone or a pharmaceutically acceptable salt thereof, as contemplated by the present invention, are any amount that accomplishes the objectives of the present invention, including those amounts and ranges provided herein.

[0289] In another aspect, bupropion or a pharmaceutically acceptable salt thereof and / or trazodone or a pharmaceutically acceptable salt thereof in a pharmaceutical composition of the present invention exhibit sustained release drug delivery upon oral consumption by a subject.

[0290] In another aspect, each of bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt in a pharmaceutical composition of the present invention exhibit sustained release drug delivery upon oral consumption by a subject.

[0291] Thus, it should be appreciated that it is preferable, in accordance with this invention, for the bupropion or a pharmaceutically acceptable salt thereof and trazodoneAttorney Docket No.49848-4040PCT or a pharmaceutically acceptable salt thereof are each administered as time-release, once-a-day or twice-a-day medications for delivering the effective amounts of bupropion and trazodone to the treated subjects.

[0292] The mechanism by which the combination of trazodone SR and bupropion SR improves the SD stated herein and induces weight loss is not entirely understood and remains unclear. Also, the mechanism by which the combination of trazodone SR and bupropion SR induces weight loss while simultaneously improving low or poor or a lack of a subjective state or sense of well-being, self-esteem, and / or self-confidence, sexual function, and sexual desire are also not entirely understood and remain unclear.

[0293] Generally speaking, however, when the combination is used for weight loss or weight loss management, SR bupropion is thought to have effects on areas of the brain involved in the regulation of food intake, sexual desire, sexual fantasies, sexual function and / or low or poor or a lack of a subjective state or sense of well-being, self-esteem, and / or self-confidence. This includes the hypothalamus, which is involved in appetite regulation, and the mesolimbic dopamine circuit, which is involved in reward pathways. In other words, bupropion enhances the dopaminergic effect and noradrenergic effect on the energy system. These are believed to be direct mechanisms of energy modulation, lipolysis, etc. Bupropion also stimulates the reward circuitry, i.e., might get better reward for food, therefore, not need more.

[0294] SR Trazodone and / or its metabolite mCPP is thought to reduce or modulate serotonin and possibly activate the 5-HT2C receptors possibly contributing to a decrease in appetite and satiety and affect mood. Trazodone through improved sleep may also play a role in added weight benefits - better sleep generally with better BMI / non-weight gain; or rather that poor sleep correlates with unhealthy weight gain.

[0295] With that said, and without being limited to any mechanism of actions or theories, it is believed that the combination achieves the objectives of the present invention:Attorney Docket No.49848-4040PCT ^ By decreasing or modulating serotonin levels and increasing dopamine and norepinephrine levels, the combination induces weight loss or affects weight. It is also believed that the metabolite of trazodone, meta- Chlorophenylpiperazine (mCPP), contributes to inducing weight loss by possibly affecting appetite, satiety and mood via its agonistic activity with the 5-HT2C receptor; ^ By decreasing or modulating serotonin levels and increasing dopamine and norepinephrine levels in the brain, the combination provides improvements in low or poor or a lack of a subjective state or sense of well-being, self- esteem, and / or self-confidence, including improvements in anhedonia, fatigue, motivation, and focus; and ^ By decreasing or modulating serotonin levels and increasing dopamine and norepinephrine levels, the combination improves sexual desire, sexual fantasies, and sexual function and counteracts suppression of sexual desires / fantasies / function and hence unmasks sexual urges thereby inducing improvements in sexual desire, sexual arousal, sexual function and / or orgasmic function, especially in patients diagnosed with SD, including FSD, HSDD, FSAD, FOD, FSIAD, and / or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like.

[0296] In other words, and without wishing to be limited to any particular theory or mechanism of action, it is believed that the combinations of the present invention work by directly and uniquely targeting the CNS by, for example, (a) inducing physiological effects from dopaminergic and noradrenergic modulation of energy, (b) increasing glucagon release and lipolysis, (c) stimulating the reward circuity, (d) stimulating prosexual benefit mechanisms, (d) counteracting certain sexual inhibitory mechanisms, (e) improving sleep, etc., and thus are able to uniquely and remarkably accomplish theAttorney Docket No.49848-4040PCT objectives of the present invention that include, amongst other things, inducing and / or maintaining weight loss, improving sexual desire and function, and / or improving the subjective state or sense of well-being, self-esteem, and / or self-confidence.

[0297] Thus, the bupropion and trazodone combinations of the present invention. when administered in the novel ratios and dosage strengths disclosed herein, uniquely and unexpectedly coordinate their mechanisms and their targets to amplify desired effects, simultaneously placing unwanted effects in opposition for a perceived cancellation of side effects, i.e., they uniquely exploit their different mechanisms and targets to stimulate the prosexual benefit and weight loss pathways while inhibiting the inhibitory sexual desire pathways to improve sexual desire and function, to induce and / or maintain weight loss and / or improve the subjective state or sense of well-being, self- esteem, and / or self-confidence. 2. COMPOUNDS OF THE INVENTION

[0298] In one aspect, the invention provides compounds capable of modulating hypoactive sexual desire disorder in a subject. Such compounds include a 5-HT2A antagonist, a 5-HT1A receptor agonist, a norepinephrine-dopamine reuptake inhibitor, and an endocrine active agent. Compositions of the invention further include a pharmaceutically acceptable carrier.

[0299] The compounds delineated herein include a 5-HT2A antagonist, that is a compound that demonstrates antagonistic activity against the 5-HT2A receptor; a norepinephrine-dopamine reuptake inhibitor; that is a compound that exhibits inhibition activity in norepinephrine-dopamine reuptake; a 5-HT1A receptor agonist, that is a compound that demonstrates agonist activity against the 5-HT1A receptor; and an endocrine active agent, that is an agent that is active in modulating the endocrine system.Attorney Docket No.49848-4040PCT

[0300] In one embodiment, the invention provides a compound (e.g., a compound herein) capable of modulating hypoactive sexual desire disorder; and pharmaceutically acceptable esters, salts, isomers and prodrugs thereof.

[0301] Naturally occurring or synthetic isomers can be separated in several ways known in the art. Methods for separating a racemic mixture of two enantiomers include chromatography using a chiral stationary phase (see, e.g., "Chiral Liquid Chromatography," W. J. Lough, Ed. Chapman and Hall, New York (1989)). Enantiomers can also be separated by classical resolution techniques. For example, formation of diastereomeric salts and fractional crystallization can be used to separate enantiomers. For the separation of enantiomers of carboxylic acids, the diastereomeric salts can be formed by addition of enantiomerically pure chiral bases such as brucine, quinine, ephedrine, strychnine, and the like. Alternatively, diastereomeric esters can be formed with enantiomerically pure chiral alcohols such as menthol, followed by separation of the diastereomeric esters and hydrolysis to yield the free, enantiomerically enriched carboxylic acid. For separation of the optical isomers of amino compounds, addition of chiral carboxylic or sulfonic acids, such as camphorsulfonic acid, tartaric acid, mandelic acid, or lactic acid can result in formation of the diastereomeric salts. 3. USES OF THE COMPOUNDS OF THE INVENTION

[0302] In one embodiment, the invention provides methods of treating hypoactive sexual desire disorder (HSDD) in a subject comprising administering to the subject a composition delineated herein. In certain embodiments, the subject is a mammal, e.g., a primate, e.g., a human. In aspect, the disease, disorder or symptom thereof in which the compounds, compositions, and methods of treatment relate to is one described in the Diagnostic and Statistical Manual of Mental Disorders 4.sup.th edition--Text Revision, (DSM-I-TRV), American Psychiatric Association.

[0303] In certain embodiments, the methods of the invention include administering to a subject a therapeutically effective amount of a compound of the invention inAttorney Docket No.49848-4040PCT combination with another pharmaceutically active compound. Examples of pharmaceutically active compounds include compounds known to treat hypoactive sexual desire disorder (HSDD) in a subject. Other pharmaceutically active compounds that may be used can be found in Harrison's Principles of Internal Medicine, Thirteenth Edition, Eds. T. R. Harrison et al. McGraw-Hill N.Y., NY; and the Physicians Desk Reference 50th Edition 1997, Oradell N.J., Medical Economics Co., the complete contents of which are expressly incorporated herein by reference. The compound of the invention and the pharmaceutically active compound may be administered to the subject in the same pharmaceutical composition or in different pharmaceutical compositions (at the same time or at different times).

[0304] Determination of a therapeutically effective hypoactive sexual desire disorder (HSDD) effective amount, a prophylactically effective hypoactive sexual desire disorder amount of the compound of the invention, can be readily made by the physician or veterinarian (the "attending clinician"), as one skilled in the art, by the use of known techniques and by observing results obtained under analogous circumstances. The dosages may be varied depending upon the requirements of the patient in the judgment of the attending clinician; the severity of the condition being treated and the particular compound being employed. In determining the therapeutically effective hypoactive sexual desire disorder amount or dose, and the prophylactically effective hypoactive sexual desire disorder amount or dose, a number of factors are considered by the attending clinician, including, but not limited to: the specific hypoactive sexual desire disorder involved; pharmacodynamic characteristics of the particular agent and its mode and route of administration; the desired time course of treatment; the species of mammal; its size, age, and general health; the specific disease involved; the degree of or involvement or the severity of the disease; the response of the individual patient; the particular compound administered; the mode of administration; the bioavailability characteristics of the preparation administered; the dose regimen selected; the kind of concurrent treatment (i.e., the interaction of the compound of the invention with other co-administered therapeutics); and other relevant circumstances.Attorney Docket No.49848-4040PCT

[0305] The dosage administration can be in a single dosage form or multiple dosage forms. The dosages can be administered concurrently, simultaneously, or sequentially. The dosages can be a single dosage immediately prior to sexual activity, or can be one or more doses daily without regard to timing prior to sexual activity. Treatment can be initiated with smaller dosages, which are less than the optimum dose of the compound. Thereafter, the dosage may be increased by small increments until the optimum effect under the circumstances is reached. For convenience, the total daily dosage may be divided and administered in portions during the day if desired. A therapeutically effective amount and a prophylactically effective amount of a compound of the invention of the invention is expected to vary from about 0.1 milligram per kilogram of body weight per day (mg / kg / day) to about 100 mg / kg / day.

[0306] The identification of those patients who are in need of prophylactic treatment for SD, such as FSD, HSDD, FSAD, FOD, FSIAD, FSP, SIAD, and / or MSD, including MHSDD, ED, PD, PE, MHSDD, MDE, MDL, MDO and the like, and / or low or poor or a lack of a subjective state of well-being, self-esteem, and / or self-confidence is well within the ability and knowledge of one skilled in the art. Certain of the methods for identification of patients which are at risk of developing SD, such as FSD, HSDD, FSAD, FOD, FSIAD, FSP, SIAD, and / or MSD, including MHSDD, ED, PD, PE, MHSDD, MDE, MDL, MDO and the like, and / or low or poor or a lack of a subjective state of well-being, self-esteem, and / or self-confidence which can be treated by the subject method are appreciated in the medical arts, such as family history, and the presence of risk factors associated with the development of that disease state in the subject patient (e.g., use of antidepressant drugs, hormonal contraceptives, antihormonal and / or cytotoxic chemotherapies, sedatives, antipsychotic drugs, antiepileptic drugs, mood stabilizer drugs, opioid drugs, alcohol, or narcotic drugs). A clinician skilled in the art can readily identify such candidate patients, by the use of, for example, clinical tests, physical examination and medical / family history.Attorney Docket No.49848-4040PCT

[0307] As used herein, "obtaining a biological sample from a subject," includes obtaining a sample for use in the methods described herein. A biological sample is described above.

[0308] In another aspect, a compound of the invention is packaged in a therapeutically effective amount with a pharmaceutically acceptable carrier or diluent. The composition may be formulated for treating a subject suffering from or susceptible to a SD, such as FSD, HSDD, FSAD, FOD, FSIAD, FSP, SIAD, and / or MSD, including MHSDD, ED, PD, PE, MHSDD, MDE, MDL, MDO and the like, and packaged with instructions to treat a subject suffering from or susceptible to a hypoactive sexual desire disorder.

[0309] The subject may be at risk of a SD, such as FSD, HSDD, FSAD, FOD, FSIAD, FSP, SIAD, and / or MSD, including MHSDD, ED, PD, PE, MHSDD, MDE, MDL, MDO and the like, may be exhibiting symptoms of SD, such as FSD, HSDD, FSAD, FOD, FSIAD, FSP, SIAD, and / or MSD, including MHSDD, ED, PD, PE, MHSDD, MDE, MDL, MDO and the like, may be susceptible to a SD, such as FSD, HSDD, FSAD, FOD, FSIAD, FSP, SIAD, and / or MSD, including MHSDD, ED, PD, PE, MHSDD, MDE, MDL, MDO and the like, and / or may have been diagnosed with a SD, such as FSD, HSDD, FSAD, FOD, FSIAD, FSP, SIAD, and / or MSD, including MHSDD, ED, PD, PE, MHSDD, MDE, MDL, MDO and the like.

[0310] If the modulation of the status indicates that the subject may have a favorable clinical response to the treatment, the subject may be treated with the compound. For example, the subject can be administered therapeutically effective dose or doses of the compound.

[0311] Kits of the invention include kits for treating SD, such as FSD, HSDD, FSAD, FOD, FSIAD, FSP, SIAD, and / or MSD, including MHSDD, ED, PD, PE, MHSDD, MDE, MDL, MDO and the like, in a subject. The kit may include a compound of the invention, for example, a compound described herein, pharmaceutically acceptable esters, salts,Attorney Docket No.49848-4040PCT and prodrugs thereof, and instructions for use. The instructions for use may include information on dosage, method of delivery, storage of the kit, etc. In aspects, the kits (and methods of using them) comprise instructions indicating that the compositions and / or treatment methods are contraindicated for (or not to be administered to) subjects that: (1) require and / or are taking CYP3A4, CYP 2B6-, or CYP 2D6-metabolized drugs; (ii) take any sex hormone other than an approved hormonal contraceptive; (iii) drink more than one alcoholic drink per day (e.g., 12-oz beer, 4-oz wine, etc).

[0312] Alternatively, the effects of the compounds of the invention can be characterized in vivo using animal models. 4. PHARMACEUTICAL COMPOSITIONS

[0313] The invention also provides a pharmaceutical composition, comprising an effective amount of a compound described herein and a pharmaceutically acceptable carrier. In a further embodiment, the effective amount is effective to treat a SD, such as FSD, HSDD, FSAD, FOD, FSIAD, FSP, SIAD, and / or MSD, including MHSDD, ED, PD, PE, MHSDD, MDE, MDL, MDO and the like, obesity, weight loss and / or maintain weight loss, and / or low or poor or a lack of a subjective state of well-being, self-esteem, and / or self-confidence, as described previously.

[0314] In an embodiment, the compound of the invention is administered to the subject using a pharmaceutically acceptable formulation, e.g., a pharmaceutically acceptable formulation that provides sustained delivery of the compound of the invention to a subject for at least 12 hours, 24 hours, 36 hours, 48 hours, one week, two weeks, three weeks, or four weeks after the pharmaceutically acceptable formulation is administered to the subject.

[0315] In certain embodiments, the pharmaceutical compositions as contemplated by the present invention are suitable for topical or oral, buccal or sublingual administration to a subject. In other embodiments, as described in detail below, the pharmaceuticalAttorney Docket No.49848-4040PCT compositions of the present invention may be specially formulated for administration in solid or liquid form, including those adapted for the following: (1) oral administration, for example, drenches (aqueous or non-aqueous solutions or suspensions), liquids, emulsions, tablets, caplets, capsules, troches, boluses, powders, granules, pastes; (2) parenteral administration, for example, subcutaneous, intramuscular or intravenous injection as, for example, a sterile solution or suspension; (3) topical application, for example, a cream, ointment, salve, balm, liquid, suspension, or spray applied to the skin; (4) intravaginally or intrarectally, for example, as a pessary, cream or foam; or (5) aerosol, for example, as an aqueous aerosol, liposomal preparation or solid particles containing the compound or composition herein.

[0316] Wetting agents, emulsifiers and lubricants, such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the compositions.

[0317] Examples of pharmaceutically-acceptable antioxidants include: (1) water soluble antioxidants, such as ascorbic acid, cysteine hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite and the like; (2) oil-soluble antioxidants, such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, alpha-tocopherol, and the like; and (3) metal chelating agents, such as citric acid, ethylenediamine tetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, and the like.

[0318] Pharmaceutical compositions containing a compound of the present invention(s) include those suitable for oral, nasal, topical (including buccal and sublingual), rectal, vaginal, aerosol and / or parenteral administration. The compositions may conveniently be presented in unit dosage form and may be prepared by any methods well known in the art of pharmacy. The amount of active ingredient which can be combined with a carrier material to produce a single dosage form will vary depending upon the host being treated, the particular mode of administration. The amount of activeAttorney Docket No.49848-4040PCT ingredient which can be combined with a carrier material to produce a single dosage form will generally be that amount of the compound which produces a therapeutic effect. Generally, out of one hundred percent, this amount will range from about 1 percent to about ninety-nine percent of active ingredient, preferably from about 5 percent to about 70 percent, more preferably from about 10 percent to about 30 percent.

[0319] Methods of preparing these compositions include the step of bringing into association a compound of the invention(s) with the carrier and, optionally, one or more accessory ingredients. In general, the formulations are prepared by uniformly and intimately bringing into association a compound of the invention with liquid carriers, or finely divided solid carriers, or both, and then, if necessary, shaping the product.

[0320] Pharmaceutical compositions of the present invention suitable for oral administration may be in the form of capsules, cachets, pills, tablets, lozenges (using a flavored basis, usually sucrose and acacia or tragacanth), powders, granules, or as a solution or a suspension in an aqueous or non-aqueous liquid, or as an oil-in-water or water-in-oil liquid emulsion, or as an elixir or syrup, or as pastilles (using an inert base, such as gelatin and glycerin, or sucrose and acacia) and / or as mouth washes and the like, each containing a predetermined amount of a compound of the invention(s) as an active ingredient. A compound may also be administered as a bolus, electuary or paste.

[0321] In solid dosage forms of the invention for oral administration (capsules, tablets, pills, dragees, powders, granules and the like), the active ingredient is mixed with one or more pharmaceutically-acceptable carriers, such as sodium citrate or dicalcium phosphate, and / or any of the following: (1) fillers or extenders, such as starches, lactose, sucrose, glucose, mannitol, and / or silicic acid; (2) binders, such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose and / or acacia; (3) humectants, such as glycerol; (4) disintegrating agents, such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate; (5) solution retarding agents, such as paraffin; (6) absorption accelerators, such as quaternary ammonium compounds; (7) wetting agents, such as, for example, acetylAttorney Docket No.49848-4040PCT alcohol and glycerol monostearate; (8) absorbents, such as kaolin and bentonite clay; (9) lubricants, such a talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof; and (10) coloring agents. In the case of capsules, tablets and pills, the pharmaceutical compositions may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugars, as well as high molecular weight polyethylene glycols and the like.

[0322] A tablet may be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared using binder (for example, gelatin or hydroxypropylmethyl cellulose), lubricant, inert diluent, preservative, disintegrant (for example, sodium starch glycolate or cross-linked sodium carboxymethyl cellulose), surface-active or dispersing agent. Molded tablets may be made by molding in a suitable machine a mixture of the powdered active ingredient moistened with an inert liquid diluent.

[0323] The tablets, and other solid dosage forms of the pharmaceutical compositions of the present invention, such as dragees, capsules, pills and granules, may optionally be scored or prepared with coatings and shells, such as enteric coatings and other coatings well known in the pharmaceutical-formulating art. They may also be formulated so as to provide slow or controlled release of the active ingredient therein using, for example, hydroxypropylmethyl cellulose in varying proportions to provide the desired release profile, other polymer matrices, liposomes and / or microspheres. They may be sterilized by, for example, filtration through a bacteria-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved in sterile water, or some other sterile injectable medium immediately before use. These compositions may also optionally contain opacifying agents and may be of a composition that they release the active ingredient(s) only, or preferentially, in a certain portion of the gastrointestinal tract, optionally, in a delayed manner. Examples of embedding compositions which can be used include polymeric substances and waxes.Attorney Docket No.49848-4040PCT The active ingredient can also be in micro-encapsulated form, if appropriate, with one or more of the above-described excipients.

[0324] Liquid dosage forms for oral administration of the compound of the invention(s) include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active ingredient, the liquid dosage forms may contain inert diluents commonly used in the art, such as, for example, water or other solvents, solubilizing agents and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor and sesame oils), glycerol, tetrahydrofuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof.

[0325] In addition to inert diluents, the oral compositions can include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, coloring, perfuming and preservative agents.

[0326] Suspensions, in addition to the active compound of the invention(s) may contain suspending agents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, and mixtures thereof.

[0327] Pharmaceutical compositions of the present invention for rectal or vaginal administration may be presented as a suppository, which may be prepared by mixing one or more compound of the invention(s) with one or more suitable nonirritating excipients or carriers comprising, for example, cocoa butter, polyethylene glycol, a suppository wax or a salicylate, and which is solid at room temperature, but liquid at body temperature and, therefore, will melt in the rectum or vaginal cavity and release the active agent.Attorney Docket No.49848-4040PCT

[0328] Compositions of the present invention which are suitable for vaginal administration also include pessaries, tampons, creams, gels, pastes, foams or spray formulations containing such carriers as are known in the art to be appropriate.

[0329] Dosage forms for the topical or transdermal administration of a compound of the invention(s) include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches and inhalants. The active compound of the invention(s) may be mixed under sterile conditions with a pharmaceutically acceptable carrier, and with any preservatives, buffers, or propellants which may be required.

[0330] The ointments, pastes, creams and gels may contain, in addition to compound of the invention(s) of the present invention, excipients, such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof.

[0331] Powders and sprays can contain, in addition to a compound of the invention(s), excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances. Sprays can additionally contain customary propellants, such as chlorofluorohydrocarbons and volatile unsubstituted hydrocarbons, such as butane and propane.

[0332] The compound of the invention(s) can be alternatively administered by aerosol. This is accomplished by preparing an aqueous aerosol, liposomal preparation or solid particles containing the compound. A nonaqueous (e.g., fluorocarbon propellant) suspension could be used. Sonic nebulizers are preferred because they minimize exposing the agent to shear, which can result in degradation of the compound.

[0333] Ordinarily, an aqueous aerosol is made by formulating an aqueous solution or suspension of the agent together with conventional pharmaceutically-acceptable carriers and stabilizers, The carriers and stabilizers vary with the requirements of theAttorney Docket No.49848-4040PCT particular compound, but typically include nonionic surfactants (Tweens, Pluronics, or polyethylene glycol), innocuous proteins like serum albumin, sorbitan esters, oleic acid, lecithin, amino acids such as glycine, buffers, salts, sugars or sugar alcohols. Aerosols generally are prepared from isotonic solutions.

[0334] Transdermal patches have the added advantage of providing controlled delivery of a compound of the invention(s) to the body. Such dosage forms can be made by dissolving or dispersing the agent in the proper medium. Absorption enhancers can also be used to increase the flux of the active ingredient across the skin. The rate of such flux can be controlled by either providing a rate controlling membrane or dispersing the active ingredient in a polymer matrix or gel.

[0335] Ophthalmic formulations, eye ointments, powders, solutions and the like, are also contemplated as being within the scope of the invention.

[0336] Pharmaceutical compositions of the invention suitable for parenteral administration comprise one or more compound of the invention(s) in combination with one or more pharmaceutically-acceptable sterile isotonic aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, or sterile powders which may be reconstituted into sterile injectable solutions or dispersions just prior to use, which may contain antioxidants, buffers, bacteriostats, solutes which render the formulation isotonic with the blood of the intended recipient or suspending or thickening agents.

[0337] Examples of suitable aqueous and nonaqueous carriers, which may be employed in the pharmaceutical compositions of the invention include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), and suitable mixtures thereof, vegetable oils, such as olive oil, and injectable organic esters, such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of coating materials, such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants.Attorney Docket No.49848-4040PCT

[0338] These compositions may also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms may be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid, and the like. It may also be desirable to include isotonic agents, such as sugars, sodium chloride, and the like into the compositions. In addition, prolonged absorption of the injectable pharmaceutical form may be brought about by the inclusion of agents which delay absorption such as aluminum monostearate and gelatin.

[0339] In some cases, in order to prolong the effect of a drug, it is desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material having poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle.

[0340] Injectable depot forms are made by forming microencapsule matrices of compound of the invention(s) in biodegradable polymers such as polylactide- polyglycolide. Depending on the ratio of drug to polymer, and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemuisions which are compatible with body tissue.

[0341] When the compound of the invention(s) are administered as pharmaceuticals, to humans and animals, they can be given per se or as a pharmaceutical composition containing, for example, 0.1 to 99.5% (more preferably, 0.5 to 90%) of active ingredient in combination with a pharmaceutically acceptable carrier.Attorney Docket No.49848-4040PCT

[0342] Regardless of the route of administration selected, the compound of the invention(s), which may be used in a suitable hydrated form, and / or the pharmaceutical compositions of the present invention, are formulated into pharmaceutically acceptable dosage forms by conventional methods known to those of skill in the art.

[0343] Actual dosage levels and time course of administration of the active ingredients in the pharmaceutical compositions of the invention may be varied so as to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient. An exemplary dose range is from 0.1 to 10 mg per day.

[0344] A preferred dose of the compound of the present invention is the maximum that a patient can tolerate and not develop serious side effects. Preferably, the compound of the invention of the present invention is administered at a concentration of about 0.001 mg to about 100 mg per kilogram of body weight, about 0.001 to about 10 mg / kg or about 0.001 mg to about 100 mg / kg of body weight. Ranges intermediate to the above-recited values are also intended to be part of the invention.

[0345] It should be understood that the methods of the present invention contemplate the use of any compounds, pharmaceutical compositions formulated compounds, and FDA-approved drug compounds discussed herein in accordance with their respective FDA-approved labels, including their respective FDA-approved dosage strengths and treatment regimens. It should also be understood that a particular dosage and treatment regimen for compound drug combinations contemplated by the methods of the present invention will depend upon the combination of the drug compounds prescribed, dosage strengths and treatment regimens, including FDA approved dosage strengths and treatment regimens, the status of the patients and the severity of the nature of the conditions to be treated. The combination drug compositions of the present invention should be prescribed by a physician or health professional, preferably a treating physician, who will consider any relevant factors, such as the patients' diagnosed condition(s) to be treated, the patients’ age and weight, the patients’ symptoms, theAttorney Docket No.49848-4040PCT severity of the patients’ symptoms, the drugs and / or drug cocktails of choice to treat the patients’ diagnosed condition(s), the treatment regimens, the dosage strengths, and the chosen routes of administration. The present invention also contemplates the safe and effective use of other dosage strengths and treatment regimens, even those that are not necessarily FDA-approved, i.e., off label use, for the drug compound combinations disclosed herein in accordance with the methods of the present invention when prescribed by a physician or other health care professional who has taken into careful consideration medical publications and possible advice from experts supporting such use.

[0346] The present disclosure will further be illustrated in the following non-limiting examples, it being understood that the examples are intended to be illustrative only and that the disclosure is not intended to be limited to the materials, conditions, process parameters and the like recited herein. All proportions are by weight unless otherwise indicated. Thus, the following examples are intended to illustrate embodiments of the present invention but not limit the scope of the present invention. EXAMPLES

[0347] The invention is further illustrated by the following Examples which are intended to illustrate but not limit the scope of the invention. Materials

[0348] Small-Molecule Compounds--bupropion, trazodone and testosterone (and their salt, solvates, hydrates, isomers, enantiomers, diasteriomers, racemates; all of which are included herein) are available from commercial sources and / or readily synthesized using methods and reagents know in the art. Bupropion is also known as, i.e., .beta.-Keto-3-chloro-N-tert-butylamphetamine, i.e., (.+-.)-2-(tert-Butylamino)-1-(3- chlorophenyl)propan-1-one; trazodone is also known as, i.e., 2-{3-[4-(3- chlorophenyl)piperazin-1-yl]propyl}[1,2,4]triazolo[4,3-a]pyrid- in-3(2H)-one.Attorney Docket No.49848-4040PCT Example 1Clinical protocol—subjects in a single blind, sequential study are administered bupropion and trazodone in increasing dosages @ 3-4 weeks each, that is, from a 3 (or 4)-week placebo baseline, to an intermediate dose (@ another 3-4 weeks), to a maximum dose (@ a final 3-4 weeks). The subjects' feedback / reports on subjective (e.g., feelings, sensations, general response) and objective (e.g., response time, performance measures, partner response) is collated and analyzed against dosage. Each study also includes one or more patient(s) serving as a control (in demonstrating the synergistic effect between the two actives) would receive only bupropion, while the second and third will each be given a different fixed dose combination products having a defined ratio of active ingredients (e.g., bupropion and trazodone). Example 2

[0350] Method. A 36 year-old healthy male volunteer in a stable marital relationship for two years with no current sexual disorders, exposed himself sequentially to four treatments, each for 4 weeks: (1) Treatment B: Instant-release (IR) Bup 150 mg in the morning and 100 mg in the evening; (2) Treatment T: IR Trz 50 mg t.i.d.; (3) Treatment Llow, IR Trz 25 mg b.i.d. plus IR Bup 150 mg in the morning and 100 mg in the evening; and (4) Treatment Lhigh, IR Trz 50 mg t.i.d. plus IR. Bup 75 mg t.i.d. A washout of 1-4 weeks occurred between each treatment. Level and frequency of sexual desire was scored daily, as not improved (O), somewhat improved (1), or markedly improved (2). Sexual events were counted, and three domains (sexual arousal, orgasm, and overall satisfaction with the event) were scored. Each of the sexual event variables was converted to a simple patient's global impression of improvement (PGI; improved or not improved today compared to pre-treatment baseline). The 3 domains of sexual event improvements were summed for analysis. Bup is already recommended as a treatment for HSDD; Trz is not. Thus, Fisher's exact test was applied post-hoc to the PGIs for Treatment B vs. Treatment Llow (Llow) and vs. Treatment Lhigh (Lhigh).Attorney Docket No.49848-4040PCT

[0351] Results. For sexual desire, the mean score with Llowand Lhighwas about twice that with Treatment B (two-tailed paired t-test, p<0.0001), and Treatment B was superior to Treatment T. For arousal, orgasm, and overall satisfaction with a sexual event, Llowwas associated with somewhat more improvements than with Treatment B in the third and fourth weeks of use. Lhigh was associated with significantly more improvements than with Treatment B in the third and fourth weeks of use and in the total for all four weeks. Fisher's exact test, two-tailed, showed the combination of bupropion plus trazodone superior, p<0.05, for the 3-domain sum of sexual event improvement. This study conducted with the combination of bupropion plus trazodone showed increased benefits in sexual arousal, orgasm, and event satisfaction, after exposure for 4 weeks, compared to either bupropion alone or trazodone alone. The effects occurred at or below the target dosage of bupropion or trazodone in their current (antidepressant) labeling.

[0352] An independent researcher then scored the desire results as unimproved=0, somewhat improved=1, and markedly improved=2. Upon the advice of the independent researcher the subject dichotomized his sexual event results in a simple daily patient's global impression of improvement: improved or not improved today (compared to pre-treatment baseline). The independent researcher, when told that the results were positive for the subject but before seeing any of the data, decided to apply categorical tests to the most obvious comparisons between treatments: for the first two weeks, the second two weeks, and for all four weeks of treatment, low-dose combination of bupropion plus trazodone vs. corresponding dose of bupropion; and high-dose the combination of bupropion plus trazodone vs. same dose of trazodone. The test used for the desire score was a two-tailed paired t test. The test used for the two-category variables was an online two-tailed Fisher's exact test. Both were from the website graphpad.com.* See Table 1. *http: / / graphpad.com / quickcalcs / chisquared1.cfmAttorney Docket No.49848-4040PCT

[0353] ‘Table 1 – Improvements in Sex Score and Sexual Events.

[0354] For sexual desire, the response to T (Treatment T) was low, to B (Treatment B) was intermediate, and to Llowand Lhighwas sometimes strong in the first two weeks and uniformly strong (improvement rated as marked every day) in the second two weeks of treatment. The differences between each dose of L vs. B were highly statistically significant, p<0.0001.

[0355] B was markedly superior to T, p<0.05 for all comparisons.

[0356] For the sum of improvements in arousal, orgasm, and overall satisfaction with a sexual event, Llow showed significantly more improvements than with B in the thirdAttorney Docket No.49848-4040PCT and fourth weeks of use, 52% vs. 20%, p<0.05. Lhighwas associated with significantly more improvements than with Bin the third and fourth weeks of use (72% vs.13%) and in the total for all four weeks (61% vs.20%). Fisher's exact test, two-tailed, showed the combination of bupropion plus trazodone superior, p<0.05, for each of these 3-domain sums of sexual event improvement.

[0357] For improvements in orgasm or overall satisfaction for a sexual event, the numbers appeared too small and the numerical trends were generally too weak to show statistically significant differences. For arousal, however, Lhigh was associated with significantly more improvements than with B in the third and fourth weeks of use (100% vs.0%) and in the total for all four weeks (91% vs.20%). Fisher's exact test, two-tailed, showed the combination of bupropion plus trazodone superior, p<0.05, for each of these 3-domain sums of sexual event improvement. A numerical trend also favored Lhigh in weeks 1-2 by ⅘ vs. ⅖ (80% vs.40%).

[0358] The applicability of these male results to female subjects with HSDD is possible given the similarities of desire dysfunction in men and women [Laumann 1999] and is to be tested next. Example 3

[0359] Additional Study Design. Further study is conducted as delineated in the Schematic below.

[0360] Schematic of Study DesignAttorney Docket No.49848-4040PCT

[0362] Week 0: Informed consent, screening evaluations [Medical, psychiatric, social / relationship, and sexual history; diagnostics], measures of sexual dysfunction, and safety evaluations [physical examination, ECG, standard laboratory safety analytes].Attorney Docket No.49848-4040PCT

[0363] Week 1: Treatment #1

[0364] Group 1

[0365] Low Dose combination of bupropion plus trazodone: 250 mg BUP+75 mg TRZ / day, given as 150 mg SR BUP in the morning and 100 mg SR BUP in the evening and 75 mg SR trazodone q.d.; and test battery. The test battery includes single-dose PK, steady-state PK and pharmacodynamics. Pharmacodynamics includes a cognitive test battery and numeric rating scales (NRS) of feeling states, which will be done in the morning of the first and last day of dosing, at pre-dose and at 1-, 2-, 4- and 8-hours post- dose. The cognitive testing battery includes choice reaction time, word recall, picture recognition, numeric and spatial working memory. The self-rated NRS of feeling states for sedation / activation includes drowsy, dizzy, nervous, agitated, and hyper. Cognitive testing will be done within -20 minutes before the hour; blood sampling will be done exactly on the hour; and VAS will be done within +15 minutes after the hour.

[0366] Or

[0367] Group 2

[0368] 150 mg SR BUP in the morning and 100 mg SR BUP in the evening.

[0369] Week 2: washout #1

[0370] Week 3: Treatment #2:

[0371] Group 1

[0372] High Dose combination of bupropion plus trazodone (250 mg BUP and 150 mg TRZ / day, given as 150 mg SR BUP in the morning and 100 mg SR BUP in the eveningAttorney Docket No.49848-4040PCT

[0373] and 150 mg SR trazodone q.d.) and test battery

[0374] Or

[0375] Group 2

[0376] 150 mg SR trazodone q.d.

[0377] Week 4: Washout #2 Example 4

[0378] Compositions of the invention can be made by combining the active agents (i.e., bupropion and trazodone) with one or more of the following excipients:

[0379] CARNAUBA WAX, CYSTEINE HYDROCHLORIDE, HYPROMELLOSES, MAGNESIUM STEARATE, CELLULOSE, MICROCRYSTALLINE, POLYETHYLENE, GLYCOL, POLYSORBATE 80, TITANIUM DIOXIDE, FD&C BLUE NO.1;

[0380] Hydroxypropyl distarch phosphate (Contramid®), Hypromellose, Sodium stearyl fumarate, Colloidal silicon dioxide, Iron Oxide Yellow, Iron Oxide Red, Talc, Polyethylene Glycol 3350, Titanium Dioxide, Polyvinyl Alcohol, Black ink (food grade). Example 5

[0381] In an open label crossover study, 4 weeks per treatment, premenopausal women with HSDD (N = 30) were treated with either (1) low-dose bupropion + trazodone (“LOR-low”) or moderate-dose bupropion + trazodone (“LOR-mod”), or (2) bupropion 300 mg / d. See Table 2 for study patient disposition.Attorney Docket No.49848-4040PCT

[0382] Table 2 – Study Patient Disposition. DISPOSITION Control LOR-low LOR-mod Subjects Receiving >=1 dose 30 28 26 Subjects completing treatment 29 26 24 Discontinued before next phase 2 (6.7%) 1 (3.6%) 3 (11.5%) Lack of Efficacy 0 0 0 Adverse Events 0 0 1* (3.8%) Administrative 2 1 2 *Discontinued due to AE of persistent clitoral engorgement and pain

[0383] Significantly more treatment responders with LOR-mod vs control bupropion 300 mg / d on FSFI-d (76% vs 38%) and FSDS-R-13 (88% vs 45%); most common AEs with moderate-dose bupropion + trazodone: dry mouth (53.8%), somnolence (34.6%), constipation (23.1%), insomnia (23.1%); discontinuation due to AEs: 3.8% for LOR-mod, 0% for bupropion 300 mg / d. See Clayton AH, Kingsberg SA, Goldstein I. Evaluation and management of hypoactive sexual desire disorder. Sex Med. 2018;6(2):59-74; Pyke, R. E., et al. "Phase IIa study of a proprietary combination of bupropion and trazodone for hypoactive sexual desire disorder (HSDD) in premenopausal women: novel responder and remitter results." Annual Meeting of American Society of Clinical Psychopharmacology.2015. See also Segraves RT, Croft H, Kavoussi R, et al. Bupropion sustained release (SR) for the treatment of hypoactive sexual desire disorder (HSDD) in nondepressed women. Journal of sex & Marital Therapy. 2001 May- Jun;27(3):303-316. DOI: 10.1080 / 009262301750257155. PMID: 11354935. See also U.S. Patent No. US-9517254-B2, U.S. Patent Publication No.20150150946-A1, and U.S. Patent Publication No.20140038985-A1.

[0384] More specifically, healthy premenopausal women from 25-50 years of age with HSDD were tested in an open-label, active-control, one-way crossover study, with three 4-week treatments of extended-release trazodone and / or sustained-release bupropion. Evaluations were made before and after each treatment. A washout of at leastAttorney Docket No.49848-4040PCT a week followed each treatment. The order of treatments was a daily standard dose of bupropion; a daily subtherapeutic dose of SR bupropion and SR trazodone (LOR-low); and a daily threshold-therapeutic dose of SR bupropion and SR trazodone (LOR-mod).

[0385] Most evaluable subjects responded to LOR-mod (at the standard thresholds for response based on minimum clinically relevant difference from baseline, 79% on Female Sexual Function Index, Desire domain, 87% on Female Sexual Distress Scale- Revised Item 13, and 79% on Patient's Global Impression of Change; each P < 0.05 vs BUP). Close to half responded to bupropion (38%, 45%, and 52%, respectively). Response to LOR-low was intermediate (not significant vs BUP). Sensitivity analyses to compensate for carryover effects supported the efficacy of LOR-mod. Elicited adverse events showed the expected profile of trazodone but led to no sedative-type dropouts or worsening on the Epworth Sleepiness Scale.

[0386] Moderate-dose LOR was generally well-tolerated and was significantly more effective than bupropion (active control). The results seem highly favorable compared to previously tested agents. See Pyke RE, Clayton AH. Dose-finding study of lorexys for hypoactive sexual desire disorder in premenopausal women. J Sex Med.2019 Dec;16(12):1885-1894; Pyke R.E., Clayton A.H. Psychological treatment trials for hypoactive sexual desire disorder: a sexual medicine critique and perspective. J Sex Med. 2015;12:2451–2458; and Pyke RE, Katz M, Segraves RT, et al. Phase IIa study of a proprietary combination of bupropion and trazodone for hypoactive sexual desire disorder (HSDD) in premenopausal women: novel responder and remitter results. Presented at: Annual Meeting of the American Society of Clinical Psychopharmacology; June 22–25, 2015; Miami, FL, USA.

[0387] More specifically, a clinical study was conducted with the bupropion / trazodone combination to treat premenopausal women for HSDD. The study's primary objective was to evaluate bupropion / trazodone combination safety, tolerability and prosexual efficacy of the bupropion / trazodone combination as compared toAttorney Docket No.49848-4040PCT bupropion, one of its constituent drugs. Other objectives included exploration of the onset and duration of action of the bupropion / trazodone combination.

[0388] The study had an adaptive, three-way crossover, open-label design. It enrolled 30 premenopausal women who met the DSM-IV-TR criteria for HSDD, and it also assessed patients for the newly defined DSM-5 Sexual Interest and Arousal Disorder. Each subject received a daily dose of bupropion as an active control for four weeks followed by a week- long washout period, then daily administration of a low dose of Lorexys for four weeks followed by another washout period, and, finally, a moderate dose of Lorexys for four weeks followed by another washout period.

[0389] The dosing and treatment regimens for the study were as follows:

[0390] Active Control: Bupropion SR 300 mg was administered once daily in the morning for four weeks.

[0391] Low Dose is combination therapy that consists of two modified-release or delayed-release drugs: bupropion and trazadone. Bupropion SR 150 mg was administered once daily in the morning and trazadone ER 75 mg was administered once daily at bedtime (“LOR-low”), each for four weeks.

[0392] Moderate Dose is also combination therapy that consist of two modified- release or delayed-release drugs: bupropion and trazadone. Bupropion SR 150 mg was administered twice daily, once in the morning and once eight (8) hours later, and trazadone ER 150 mg was administered once daily at bedtime (“LOR-mod”), each for four weeks.

[0393] Patients self-evaluated weekly with questionnaires and were assessed during eight clinic visits. Outcome measures for efficacy included validated self-rated scales of Sexual Function and Sexual Distress and global change. Outcome measures for safety included comprehensive evaluations of symptoms and vital signs, plus standardAttorney Docket No.49848-4040PCT laboratory studies and electrocardiograms. The study was conducted at two clinical sites in the U.S.

[0394] Materials and Methods:

[0395] This was an open-label crossover study in non-depressed, otherwise healthy patients with DSM-IV-TR HSDD, aged 25-50 years, with four weeks per treatment. With n=30 and 33% more Lorexys responders vs. Bupropion SR, the power at a =0.05 was 80%. Four weeks of Bupropion SR at 300 mg / day and a washout was followed by four weeks of Lorexys low- dose (LOR-low), i.e., Bupropion SR plus Trazodone ER at doses lower than the labeled doses, followed by another washout and four weeks of Lorexys moderate-dose (LOR-mod; 2x LOR-low).The primary efficacy endpoint was Female Sexual Function Index Desire domain (FSFI-d); the key secondary was Female Sexual Distress Scale-Revised (FSDS-R). Analyses included % responders and % remitters from the first baseline, using standard definitions for FSFI-d and FSDS- R item 13 (FSDS-R-i13), plus Patient's Global Impression of Change (PGIC). See Table 3, Table 4 and ¶161 above. A third key was an analysis of weight change as determined by weight measure at screening and at final visit. See Tables 5-11 below.

[0396] Results

[0397] Five patients (17%) discontinued for administrative reasons; one (4%) discontinued for adverse events, on LOR-mod. See Tables 2-4 below shows responder and remitter rates with LOR-mod; rates with LOR-low were intermediate and non- significant vs. bupropion.

[0398] Conclusion

[0399] LOR-mod was highly superior to bupropion in non-depressed, otherwise healthy, premenopausal HSDD to Bupropion SR alone in the treatment of premenopausal women for HSDD. See Table 3.Attorney Docket No.49848-4040PCT

[0400] Table 3 – Responder and Remitter Rates.

[0401] As to the Patient’s Global Impression of Change, that is % improved. See Table 4.

[0402] Table 4 - Patient’s Global Impression of Change: % improved. All Patients With End-Of-Treatment Evaluation Drug n = subjects Moderately, Much or Statistically Much or Very Much significant Very Much Improved Improved Bupropion 29 24% 6% n.s.* Control LOR-low 26 42% 18% n.s.* LOR-mod 24 58% 25% p < 0.05 *n.s.: difference from bupropion control not statistically significant

[0403] Turning to the weight loss responders, 50% had an average weight loss of about 5.1%, 25% of the responders experienced ≥ 6% weight loss, and a maximum weight loss achieved was about 10.2%. See Tables 6-9.Attorney Docket No.49848-4040PCT

[0404] In this same four-week, open label study, that involved the 24 subjects that completed the LOR-mod four-week treatment, the LOR-mod, the combination of SR bupropion and ER trazodone surprisingly and unexpectedly induced weight loss in 17 or about 71% of the subjects. About 50% of the subjects lost greater than 2 lbs of body weight and about 25% of the subjects lost about 6% of body weight or more. The maximum weight lost was about 10.2%. In the 50% cohort that lost greater than 2 lbs of body weight, the range in lost body weight was from about 5% to about 10%, averaging a weight loss of about 5.1%. Seven patients in this four-week open label study, or about 29%, either did not lose weight or gained weight. See this Example 5, and Tables 5-11.

[0405] Table 5 illustrates individualized weight change in lbs. from initial screen to final study visit, V7, in the four-week open label study described in this Example 5.

[0406] Table 5 – Weight Change.

[0407] Tables 6-10 illustrate tabulated individualized and group weight loss results from the four-week open label study described in this Example 5. Tables 6-8 are aAttorney Docket No.49848-4040PCT continuation for each of the 24 subject numbers identified vertically at the start of Table 6.

[0408] Table 11 is a list of abbreviated definitions used in Tables 5-10.

[0409] Table 6 - Tabulated Individualized and Group Weight Loss Results.Attorney Docket No.49848-4040PCT

[0410] Table 7 - Tabulated Individualized and Group Weight Loss (Table 6 continued).Attorney Docket No.49848-4040PCT

[0411] Table 8 - Tabulated Individualized and Group Weight Loss Results (Table 6 continued).

[0412] Table 9 is a composite of Tables 6-8 and Table 11 and illustrates tabulated individualized and group weight loss or gain results from the four-week open label study described in this Example 5.Attorney Docket No.49848-4040PCT

[0413] Table 9 – A Composite of Tables 6-8 and 11.

[0414] Table 10 is a listing of the individual weight changes in lbs. for the 24 subjects who completed the 4-week LOR-mod study arm, which is also depicted in Tables 6-9.

[0415] Table 10 – Weight Loss or Weight Gain Results of Study. No of Subject Screening V7 ^ in Weight Weight Subjects No. Weight in Weight Weight Lost in Gain in lbs in lbs lbs lbs lbs 1 985 149 147 -2 2 --- 2 986 192 186 -6 6 --- 3 987 133 132 -1 1 --- 4 989 192 193 +1 --- 1 5 990 167 166 -1 1 --- 6 992 133 135 +2 --- 2 7 993 149 146 -3 3 --- 8 994 157 159 +2 --- 2Attorney Docket No.49848-4040PCT 9 995 140 142 +2 --- 2 10 996 139 136 -3 3 --- 11 997 141 133 -8 8 --- 12 999 149 147 -2 2 --- 13 1000 135 126 -9 9 --- 14 1001 177 177 0 --- 0 15 1004 120 116 -4 4 --- 16 1006 146 137 -9 9 --- 17 1007 188 191 3 --- 3 18 1008 151 146 -5 5 --- 19 1009 160 150 -10 10 --- 20 1010 163 166 +3 --- 3 21 1011 187 182 -5 5 --- 22 1012 108 97 -11 11 --- 23 1015 131 119 -12 12 --- 24 1016 136 135 -1 1 ---

[0416] Table 11 – Listing of Abbreviation Definitions used in Tables 5 – 10 and Study Summary of Weight Loss Results.Attorney Docket No.49848-4040PCT

[0417] The disclosures of each and every patent, patent application, publication, web address and the like cited herein are hereby incorporated herein by reference in their entireties as if each has been fully set forth herein.

[0418] The recitation of a listing of chemical groups in any definition of a variable herein includes definitions of that variable as any single group or combination of listed groups. The recitation of an embodiment for a variable herein includes that embodiment as any single embodiment or in combination with any other embodiments or portions thereof. The recitation of an embodiment herein includes that embodiment as any single embodiment or in combination with any other embodiments or portions thereof.

[0419] Although the invention has been disclosed with reference to specific embodiments, it is apparent that other embodiments and variations of the invention may be devised by others skilled in the art without departing from the true spirit and scope of the invention. The claims are intended to be construed to include all such embodiments and equivalent variations.

Claims

Attorney Docket No.49848-4040PCT What is claimed is:

1. A method for treating a subject suffering from sexual function (SD) and / or effecting weight loss in a subject who needs, desires or has been instructed by a health provider to lose weight, said method comprising: administering an effective amount of a first compound and an effective amount of a second compound to the subject who needs SD treatment and / or who needs, desires or has been instructed to lose weight to treat the subject to effect weight loss in the subject; wherein said first compound is bupropion or a pharmaceutically acceptable salt thereof and said second compound is trazodone or a pharmaceutically acceptable salt thereof.

2. The method of claim 1, wherein said administration step comprises orally administering said first and second compounds to the subject.

3. The method of claims 1 or 2, wherein the first compound is in a first oral dosage form suitable for oral administration and said second compound is in a second oral dosage form suitable for oral administration, wherein the first and second oral dosage forms are each modified-release dosage forms.

4. The method of claim 3, wherein the first oral modified-dosage form is a capsule, a caplet, a cachet, a pill, a tablet, a dragee, a lozenge, a powder, or granules and the second oral modified-dosage form is a capsule, a caplet, a cachet, a pill, a tablet, a dragee, a lozenge, a powder or granules.

5. The method of claims 1 or 2, wherein a solid dosage form is a unitary solid dosage form suitable for oral administration and the unitary solid dosage form includes the first and second compounds.Attorney Docket No.49848-4040PCT 6. The method of claim 5, wherein the unitary solid dosage form is a modified-release dosage form.

7. The method of claim 5, wherein the modified-release dosage form delays release of the first and second compounds from the modified-release dosage form following said oral administration of the modified-release dosage form to the subject.

8. The method of claim 7, wherein the modified-release dosage form is a a capsule, a caplet, a cachet, a pill, a tablet, a dragee, a lozenge, a powder or granules.

9. The method of claim 1, wherein said administration step comprises: orally administering the first and second compounds to the subject; wherein the first and second compounds are formulated into a single solid dosage form; and wherein the single solid dosage form is a sustained release solid dosage form suitable for oral administration and for delaying release of the first and second compounds from the sustained release solid dosage form following said oral administration of the sustained-release solid dosage form to the subject.

10. The method of claim 9, wherein the sustained release dosage form is a capsule, a caplet, a caplet, a cachet, a pill, a tablet, a dragee, a lozenge, a powder or granules.

11. The method of claim 1, wherein the subject is diagnosed or suffering with sexual disorder or sexual dysfunction (SD), wherein said method effects improvement of the subject’s SD, and wherein the SD is selected from a group of SDs consisting of female sexual disorder (FSD), female sexual arousal disorder (FSAD), female sexual interest / arousal disorder (FSIAD), female hypoactive sexual desire disorder (HSDD), female orgasmic disorder (FOD), female sexual pain disorder (FSPD), sexual interest arousal disorder (SIAD), male sexual disorder (MSD), male hypoactive sexual desire disorder (MSHDD), erectile dysfunction (ED), Pyronine’s disease (PD), male prematureAttorney Docket No.49848-4040PCT ejaculation (MPE), male delayed ejaculation (MDE), male decreased libido (MDL), male dry orgasm (MDO), and any appropriate combination thereof.

12. The method of claims 1 or 11, wherein the subject is diagnosed or suffering with low or poor subjective well-being and / or self-esteem, and wherein said method effects improvement of the subject’s subjective well-being and / or self-esteem.

13. The method of claims 1-10, wherein the subject is diagnosed or suffering with a symptom’s of a SD, wherein said method effects improvements of the subject’s SD symptoms, and wherein the SD is selected from a group of SDs consisting of female sexual disorder (FSD), female sexual arousal disorder (FSAD), female sexual interest / arousal disorder (FSIAD), female hypoactive sexual desire disorder (HSDD), female orgasmic disorder (FOD), female sexual pain disorder (FSPD), sexual interest arousal disorder (SIAD), male sexual disorder (MSD), male hypoactive sexual desire disorder (MSHDD), erectile dysfunction (ED), Pyronine’s disease (PD), male premature ejaculation (MPE), male delayed ejaculation (MDE), male decreased libido (MDL), male dry orgasm (MDO), and any appropriate combination thereof, and wherein the subject is further diagnosed or suffering with low or poor subjective well-being and / or self-esteem, and wherein said method effects improvement of the subject’s subjective well-being and / or self-esteem.

14. The method of claims 1-9 show enhanced effects of SD and / or weight loss when the subject is treated with a combination of the said bupropion and trazodone, compared to treatment of the subject with either bupropion or trazodone alone at the same respective dosage strengths.

15. The method of claims 10-13 show enhanced effects of SD and / or weight loss when the subject is treated with a combination of the said bupropion and trazodone, compared to treatment of the subject with either bupropion or trazodone alone at the same respective dosage strengths.Attorney Docket No.49848-4040PCT 16. The method of claims 1-15, wherein the subject loses about 5% of weight when the said weight loss method is followed by the subject in accordance with a treatment regimen.

17. The method of claims 1-15, wherein the subject loses about ≥ 6% of weight when the said weight loss method is followed by the subject in accordance with a treatment regimen..

18. The method of claims 1-15, wherein the subject loses about 10.2% of weight when the said weight loss method is followed by the subject in accordance with a treatment regimen..

19. The method of claims 1-18, wherein the trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 250 mg.

20. The method of claims 1-18, wherein the trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 300 mg.

21. The method of claims 1-18, wherein the trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 250 mg.

22. The method of claims 1-18, wherein the trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 300 mg.

23. The methods of claims 1-18, wherein the trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 150 mg.

24. The methods of claims 1-18, wherein the trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 150 mg.

25. A method of treating a subject who desires to lose weight, said method comprises: (a) administering a weight loss effective amount of a first compound and a weight loss effective amount of a second compound to the subject to affect the subject’sAttorney Docket No.49848-4040PCT weight, wherein said first compound is bupropion or a pharmaceutically acceptable salt thereof and said second compound is trazodone or a pharmaceutically acceptable salt thereof, wherein the weight loss activity of said first and second compounds is enhanced compared to the administration of the same amount of either compound alone; and (b) administering said first compound and said second compound to the subject until the subject achieves a desired weight.

26. The method of claim 25, wherein said method comprises the further step of administering said first compound and said second compound to the subject to maintain the desired weight.

27. A pharmaceutical composition for affecting weight loss comprising: (a) a sustained-release formulation of bupropion or a pharmaceutically acceptable salt thereof in an amount effective to induce weight loss in a subject; and (b) a sustained-release formulation of trazodone or a pharmaceutically acceptable salt thereof in an amount effective to induce weight loss in a subject; wherein said pharmaceutical composition is a fixed combination single sustained-release dosage form suitable for oral administration.

28. The pharmaceutical composition of claim 27, wherein the trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 250 mg.

29. The pharmaceutical composition of claim 27, wherein the trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 300 mg.

30. The pharmaceutical composition of claim 27, wherein the trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 250 mg.

31. The pharmaceutical composition of claim 27, wherein the trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 300 mg.Attorney Docket No.49848-4040PCT 32. The pharmaceutical composition of claim 27, wherein the trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 150 mg.

33. The pharmaceutical composition of claim 27, wherein the trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 150 mg.

34. A pharmaceutical composition for affecting weight loss comprising: (a) a sustained-release formulation of bupropion or a pharmaceutically acceptable salt thereof in an amount effective to induce weight loss in a subject; and (b) a sustained-release formulation of trazodone or a pharmaceutically acceptable salt thereof in an amount effective to enhance the weight loss effect of the bupropion or salt thereof; wherein said pharmaceutical composition is a single oral dosage form fixed combination suitable for oral administration.

35. The pharmaceutical composition of claim 34, wherein the trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 250 mg.

36. The pharmaceutical composition of claim 34, wherein the trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 300 mg.

37. The pharmaceutical composition of claim 34, wherein the trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 250 mg.

38. The pharmaceutical composition of claim 34, wherein the trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 300 mg.

39. The pharmaceutical composition of claim 34, wherein the trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 150 mg.

40. The pharmaceutical composition of claim 34, wherein the trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 150 mg.Attorney Docket No.49848-4040PCT 41. A pharmaceutical composition of treating a subject who is in need of weight loss treatment, said method comprises administering to the subject a 5-HT2A antagonist and a norepinephrine-dopamine reuptake inhibitor to treat the patient’s sexual disorder and the patient’s obesity or the patient’s overweight to treat the subject’s obesity or for being overweight.

42. The pharmaceutical composition of claim 41, wherein the 5-HT2A antagonist is also a 5-HT1A receptor agonist.

43. The pharmaceutical composition of claim 42, wherein the 5-HT2A antagonist and 5-HT1A receptor agonist is trazodone or a pharmaceutically acceptable salt thereof, and the norepinephrine-dopamine reuptake inhibitor is bupropion or a pharmaceutically acceptable salt thereof.

44. The pharmaceutical composition of claim 43, wherein the trazodone is in a dosage range of about 25 mg to about 450 mg and the bupropion is in a dosage range of about 200 mg to about 450 mg.

45. A method of treating a sexual disorder or dysfunction (SD) in subject who is suffering from a sexual disorder and needs to lose weight and who is need of treatment for the sexual disorder and weight, said method comprises administering to the subject a 5-HT2A antagonist and a norepinephrine-dopamine reuptake inhibitor to treat the patient’s sexual disorder and the subject’s weight.

46. The method of claim 45, wherein the 5-HT2A antagonist is also a 5-HT1A receptor agonist.

47. The method of claim 46, wherein the 5-HT2A antagonist is also and 5-HT1A receptor agonist is trazodone or a pharmaceutically acceptable salt thereof, and the norepinephrine-dopamine reuptake inhibitor is bupropion or a pharmaceutically acceptable salt thereof.Attorney Docket No.49848-4040PCT 48. The method of claim 47, wherein the trazodone is in a dosage range of about 25 mg to about 450 mg and bupropion is in a dosage range of about 200 mg to about 450 mg.

49. The method of claim 48, wherein the SD is female sexual disorder (FSD).

50. The method of claim 48, wherein the SD is female orgasm disorder (FOD) or female pain disorder (FPD).

51. The method of claim 48, wherein the SD is female sexual arousal disorder (FSAD) or female sexual interest / arousal disorder (FSIAD).

52. The method of claim 48, wherein the SD is female hypoactive sexual arousal disorder (HSDD).

53. The method of claim 48, wherein the SD is sexual interest arousal disorder (SIAD).

54. The method of claim 48, wherein the SD is male sexual disorder (MSD).

55. The method of claim 54, wherein the MSD is selected from a group of MSDs consisting of male hypoactive sexual desire disorder (MSHDD), erectile dysfunction (ED), Pyronine’s disease (PD), male premature ejaculation (MPE), male delayed ejaculation (MDE), male decreased libido (MDL), male dry orgasm (MDO) and combinations thereof.

56. A method of treating a sexual disorder or sexual dysfunction (SD) and low or poor subjective state of well-being, self-esteem, and / or self-confidence in an obese or overweight subject who is suffering from a sexual disorder, low or poor subjective state of well-being, self-esteem and / or self-confidence and who is need of treatment for the SD, low or poor subjective state of well-being, self-esteem and / or self-confidence and obesity or for being overweight, said method comprises administering to the obese or overweight subject a 5-HT2A antagonist and a norepinephrine-dopamine reuptakeAttorney Docket No.49848-4040PCT inhibitor to treat the patient’s SD, low or poor subjective state of well-being, self-esteem and / or self-confidence, and the patient’s obesity or the patient’s overweight.

57. The method of claim 53, wherein the 5-HT2A antagonist is also a 5-HT1A receptor agonist.

58. The method of claim 54, wherein the 5-HT2A antagonist and 5-HT1A receptor agonist is trazodone or a pharmaceutically acceptable salt thereof, and the norepinephrine-dopamine reuptake inhibitor is bupropion or a pharmaceutically acceptable salt thereof.

59. The method of claim 55, wherein the trazodone is in a dosage range of about 25 mg to about 450 mg and the bupropion is in a dosage range of about 200 mg to about 450 mg.

60. The method of claim 56, wherein the SD is female orgasm disorder (FOD) or female pain disorder (FPD).

61. The method of claim 56, wherein the SD is female sexual arousal disorder (FSAD) or female sexual interest / arousal disorder (FSIAD).

62. The method of claim 56, wherein the SD is female hypoactive sexual arousal disorder (HSDD).

63. The method of claim 56, wherein the SD is sexual interest arousal disorder (SIAD) or female sexual interest / arousal disorder (FSIAD).

64. The method of claim 56, wherein the SD is male sexual disorder (MSD).

65. The method of claim 64, wherein the MSD is selected from a group of MSDs consisting of is male hypoactive sexual disorder (MSHDD), erectile dysfunction (ED),Attorney Docket No.49848-4040PCT Pyronine’s disease (PD), male premature ejaculation (MPE), male delayed ejaculation (MDE), male decreased libido (MDL), male dry orgasm (MDO) and combinations thereof.

66. The method of claim 45, wherein the trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 250 mg.

67. The method of claim 45, wherein the trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 300 mg.

68. The method of claim 45, wherein the trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 250 mg.

69. The method of claim 45, wherein the trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 300 mg.

70. The method of claim 45, wherein the trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 150 mg.

71. The method of claim 45, wherein the trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 150 mg.

72. A weight loss and / or weight maintenance method for effecting weight loss and / or weight maintenance in a subject who needs, desires or has been instructed by a health provider to lose weight and / or maintain weight whether or not the weight maintenance follows weight loss by the subject, comprising: orally administering an effective amount of a first compound and an effective amount of a second compound to the subject to treat the subject to effect weight loss or weight maintenance by the subject; wherein the said first compound is bupropion or a pharmaceutically acceptable salt thereof and the said second compound is trazodone or a pharmaceutically acceptable salt thereof;Attorney Docket No.49848-4040PCT wherein the said first compound and the said second compound are formulated into dosage forms suitable for oral combination administration; wherein the oral dosage form (i) is a single combination oral dosage form comprising the said bupropion and the said trazodone, or (ii) is a first distinct, separate oral dosage form comprising the said bupropion, and a second distinct, separate oral dosage form comprising the said trazodone; and wherein (1) the trazadone dosage strengths and the bupropion dosage strengths are selected from a group of combination dosage strengths consisting of (a) trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 250 mg, (b) trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 300 mg, (c) trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 250 mg, (d) trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 300 mg, (e) trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 150 mg, and (f) trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 150 mg, or (2) the bupropion is in a dosage strength range and the trazadone is in a dosage strength range selected from a group of combination dosage strength ranges consisting of (a) bupropion in a dosage strength range of 100-300 mg and trazodone in a dosage strength range of 75-150 mg, (b) comprising bupropion in a dosage strength range of 225-300 mg and comprising trazodone in a dosage strength range of 75-150 mg, (c) bupropion in a dosage strength range of 100-275 mg and comprising trazodone in a dosage strength range of 50-100 mg, and (d) bupropion in a dosage strength range of 200-275 mg and comprising trazodone in a dosage strength range of 50-100 mg; and whereby, the said oral treatment method induces the subject’s weight loss and / or weight maintenance when the bupropion and trazodone are administered orally to the subject in accordance with a treatment regimen.

73. The weight loss and / or weight maintenance method of claim 72, wherein the said oral treatment method includes the further step of:Attorney Docket No.49848-4040PCT orally administering the said single, combination oral dosage form to the subject at least once daily in accordance with the treatment regimen.

74. The weight loss and / or weight maintenance method of claim 72, wherein the said oral treatment method includes the further step of: orally administering the said first distinct, separate oral dosage form and the said second distinct, separate oral dosage form to the subject concurrently, simultaneously, or sequentially.

75. The weight loss and / or weight maintenance method of claim 72, including the further step of: orally administering the said first distinct, separate oral dosage form and the said second distinct, separate oral dosage form to the subject concurrently, simultaneously, or sequentially at least once daily in accordance with the treatment regimen.

76. The weight loss and / or weight maintenance method of claim 72, wherein the said single, combination oral dosage form, the said first distinct, separate oral dosage form, and the said second distinct, separate oral dosage form are solid oral dosage forms.

77. The weight loss and / or weight maintenance method of claim 76, wherein the said solid oral dosage forms are selected from a group of solid dosage forms comprising capsules, tablets, pills, dragees, powders, granules, cachets, and lozenges.

78. The weight loss and / or weight maintenance method of claim 76, wherein the oral solid dosage forms are controlled-release, delayed-release, extended-release, modified- release, or sustained-release solid dosage form.

79. The weight loss and / or weight maintenance method of claim 78, wherein the solid oral dosage forms provide sustained delivery of the bupropion and sustained delivery of the trazodone to the subject for at least about 12 hours after the solid oral dosage forms are administered to the subject.Attorney Docket No.49848-4040PCT 80. The weight loss and / or weight maintenance of claim 72 shows enhanced effects of weight loss and / or weight maintenance when the subject is treated with a combination of the said bupropion and trazodone, compared to treatment of the subject with either bupropion or trazodone alone at the same respective dosage strengths.

81. The weight loss and / or weight maintenance method of claim 72, wherein the subject loses between about 5% and 10.2% of weight when the said oral treatment method is followed by the subject in accordance with the treatment regimen.

82. The weight loss and / or weight maintenance method of claim 72, wherein the subject loses between about 5% and 10.2% of weight when the said oral treatment method is followed by the subject in accordance with the treatment regimen for at least about 4 weeks.

83. The weight loss and / or weight maintenance method of claim 72, wherein the subject is overweight.

84. The weight loss and / or weight maintenance method of claim 72, wherein the subject is obese.

85. The weight loss and / or weight maintenance method of claim 72, wherein the subject suffers from a sexual disorder or sexual dysfunction (SD).

86. The weight loss and / or weight maintenance method of claim 72, wherein the subject suffers from or is in a state of low or poor well-being, self-esteem and / or self- confidence.

87. A method for orally treating a subject for sexual function who needs or desires sexual function improvement, said oral treatment method for improving the subject’s sexual function comprises:Attorney Docket No.49848-4040PCT orally administering an effective amount of a first compound and an effective amount of a second compound to the subject who needs or desires to improve his or her sexual function; wherein the said first compound is bupropion or a pharmaceutically acceptable salt thereof and the said second compound is trazodone or a pharmaceutically acceptable salt thereof; wherein the said first compound and the said second compound are formulated into dosage forms suitable for oral combination administration; wherein the oral dosage form (i) is a single combination oral dosage form comprising the said bupropion and the said trazodone, or (ii) is a first distinct, separate oral dosage form comprising the said bupropion, and a second distinct, separate oral dosage form comprising the said trazodone; wherein (1) the trazadone dosage strengths and the bupropion dosage strengths are selected from a group of combination dosage strengths consisting of (a) trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 250 mg, (b) trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 300 mg, (c) trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 250 mg, (d) trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 300 mg, (e) trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 150 mg, and (f) trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 150 mg, or (2) the bupropion is in a dosage strength range and the trazadone is in a dosage strength range selected from a group of combination dosage strength ranges consisting of (a) bupropion in a dosage strength range of 100-300 mg and trazodone in a dosage strength range of 75-150 mg, (b) comprising bupropion in a dosage strength range of 225-300 mg and comprising trazodone in a dosage strength range of 75-150 mg, (c) bupropion in a dosage strength range of 100-275 mg and comprising trazodone in a dosage strength range of 50-100 mg, and (d) bupropion in a dosage strength range of 200-275 mg and comprising trazodone in a dosage strength range of 50-100 mg; andAttorney Docket No.49848-4040PCT whereby, the said oral treatment method improves the subject’s sexual function when the bupropion and trazodone are administered orally to the subject in accordance with a treatment regimen.

88. The oral treatment method of claim 87, wherein the said oral treatment method includes the further step of: orally administering the said single, combination oral dosage form to the subject at least once daily in accordance with the treatment regimen.

89. The oral treatment method of claim 87, wherein the said oral treatment method includes the further step of: orally administering the said first distinct, separate oral dosage form and the said second distinct, separate oral dosage form to the subject concurrently, simultaneously, or sequentially.

90. The oral treatment method of claim 87, including the further step of: orally administering the said first distinct, separate oral dosage form and the said second distinct, separate oral dosage form to the subject concurrently, simultaneously, or sequentially at least once daily in accordance with the treatment regimen.

91. The oral treatment method of claim 87, wherein the said single combination oral dosage form, the said first distinct, separate oral dosage form, and the said second distinct, separate oral dosage form are solid oral dosage forms.

92. The oral treatment method of claim 91, wherein the said solid oral dosage forms are selected from a group of solid dosage forms comprising capsules, caplets, tablets, pills, dragees, powders, granules, cachets, and lozenges.

93. The oral treatment method of claim 91, wherein the oral solid dosage forms are controlled-release, delayed-release, extended-release, modified-release, or sustained- release solid dosage form.Attorney Docket No.49848-4040PCT 94. The oral treatment method of claim 93, wherein the solid oral dosage forms provide sustained delivery of the bupropion and sustained delivery of the trazodone to the subject for at least about 12 hours after the solid oral dosage forms are administered to the subject.

95. The oral treatment method of claim 87 shows enhanced effects of weight loss and / or weight maintenance when the subject is treated with a combination of the said bupropion and trazodone, compared to treatment of the subject with either bupropion or trazodone alone at the same respective dosage strengths.

96. The oral treatment method of claim 87, wherein the subject loses between about 5% and 10.2% of weight when the said oral treatment method is followed by the subject in accordance with the treatment regimen.

97. The oral treatment method of claim 87, wherein the subject loses between about 5% and 10.2% of weight when the said oral treatment method is followed by the subject in accordance with the treatment regimen for at least about 4 weeks.

98. The oral treatment method of claim 87, wherein the subject is overweight.

99. The oral treatment method of claim 87, wherein the subject is obese.

100. The oral treatment method of claim 87, wherein the sexual function is a sexual disorder or sexual dysfunction (SD), and wherein the SD is selected from a group of SDs comprising female sexual dysfunction (FSD), female sexual arousal disorder (FSAD), female sexual interest / arousal disorder FSIAD), female hypoactive sexual desire disorder (HSDD), female orgasmic disorder (FOD), female pain disorder (FPD), sexual interest arousal disorder (SIAD), male sexual disorder (MSD), male hypoactive sexual desire disorder (MSHDD), erectile dysfunction (ED), Pyronine’s disease (PD), male premature ejaculation (MPE), male delayed ejaculation (MDE), male decreased libido (MDL), male dry orgasm (MDO).Attorney Docket No.49848-4040PCT 101. The oral treatment method of claim 87, wherein the subject suffers from or is in a state of low or poor well-being, self-esteem and / or self-confidence.

102. A pharmaceutical composition for oral administration for treating a subject for sexual function and / or for treating the subject for weight loss and / or for weight maintenance who needs or desires to improve his or her sexual function and / or who needs, desires or has been instructed to lose weight and / or maintain weight, whether or not the weight maintenance follows weight loss by the subject, said pharmaceutical composition comprising: an effective amount of a first compound, an effective amount of a second compound, and a pharmaceutically acceptable carrier and / or excipient; wherein the said first compound is bupropion or a pharmaceutically acceptable salt thereof and the said second compound is trazodone or a pharmaceutically acceptable salt thereof; wherein the said first compound and the said second compound are formulated into dosage forms suitable for oral combination administration; wherein the oral dosage form (i) is a single combination oral dosage form comprising the said bupropion and the said trazodone, or (ii) is a first distinct, separate oral dosage form comprising the said bupropion, and a second distinct, separate oral dosage form comprising the said trazodone; wherein (1) the trazadone dosage strengths and the bupropion dosage strengths are selected from a group of combination dosage strengths consisting of (a) trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 250 mg, (b) trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 300 mg, (c) trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 250 mg, (d) trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 300 mg, (e) trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 150 mg, and (f) trazodone is in a dosage strength of about 150 mg andAttorney Docket No.49848-4040PCT the bupropion is in a dosage strength of about 150 mg, or (2) the bupropion is in a dosage strength range and the trazadone is in a dosage strength range selected from a group of combination dosage strength ranges consisting of (a) bupropion in a dosage strength range of 100-300 mg and trazodone in a dosage strength range of 75-150 mg, (b) comprising bupropion in a dosage strength range of 225-300 mg and comprising trazodone in a dosage strength range of 75-150 mg, (c) bupropion in a dosage strength range of 100-275 mg and comprising trazodone in a dosage strength range of 50-100 mg, and (d) bupropion in a dosage strength range of 200-275 mg and comprising trazodone in a dosage strength range of 50-100 mg; and wherein said pharmaceutical composition improves the subject’s sexual function and effectuates weight loss and / or weight maintenance when said pharmaceutical composition is administered orally to the subject in accordance with a treatment regimen.

103. The pharmaceutical composition of claim 102, wherein the said single combination oral dosage form is suitable for at least once daily oral administration in accordance with the treatment regimen.

104. The pharmaceutical composition of claim 102, wherein the said first distinct, separate oral dosage form and the said second distinct, separate oral dosage form are suitable for concurrent, simultaneous, or sequential oral administration in accordance with the treatment regimen.

105. The pharmaceutical composition of claim 102, wherein the said first distinct, separate oral dosage form and the said second distinct, separate oral dosage form are suitable for concurrent, simultaneous, or sequential oral administration at least once daily in accordance with the treatment regimen.

106. The pharmaceutical composition of claim 102, wherein the said single combination oral dosage form, the said first distinct, separate oral dosage form, and the said second distinct, separate oral dosage form are solid oral dosage forms.Attorney Docket No.49848-4040PCT 107. The pharmaceutical composition of claim 106, wherein the said solid oral dosage forms are selected from a group of solid dosage forms comprising capsules, tablets, pills, dragees, powders, granules, cachets, and lozenges.

108. The pharmaceutical composition of claim 106, wherein the oral solid dosage forms are controlled-release, delayed-release, extended-release, modified-release, or sustained-release solid dosage form.

109. The pharmaceutical composition of claim 108, wherein the solid oral dosage forms provide sustained delivery of the bupropion and sustained delivery of the trazodone to the subject for at least about 12 hours after the solid oral dosage forms are administered to the subject.

110. The pharmaceutical composition of claim 102 shows enhanced effects of weight loss and / or weight maintenance when the subject is treated with a combination of the said bupropion and trazodone, compared to treatment of the subject with either bupropion or trazodone alone at the same respective dosage strengths.

111. The pharmaceutical composition of claim 102, wherein the subject loses between about 5% and 10.2% of weight when the said oral treatment method is followed by the subject in accordance with the treatment regimen.

112. The pharmaceutical composition of claim 102, wherein the subject loses between about 5% and 10.2% of weight when the said oral treatment method is followed by the subject in accordance with the treatment regimen for at least about 4 weeks.

113. The pharmaceutical composition of claim 102, wherein the subject is overweight.

114. The pharmaceutical composition of claim 102, wherein the subject is obese.

115. The pharmaceutical composition of claim 102, wherein the sexual function is a sexual disorder or sexual dysfunction (SD), and wherein the SD is selected from a groupAttorney Docket No.49848-4040PCT of SDs comprising female sexual female sexual disorder (FSD), female sexual arousal disorder (FSAD), female sexual interest / arousal disorder (FSIAD), female hypoactive sexual desire disorder (HSDD), female orgasmic disorder (FOD), female pain disorder (FPD), sexual interest arousal disorder (SIAD), male sexual disorder (MSD), male hypoactive sexual desire disorder (MSHDD), erectile dysfunction (ED), Pyronine’s disease (PD), male premature ejaculation (MPE), male delayed ejaculation (MDE), male decreased libido (MDL), male dry orgasm (MDO).

116. The pharmaceutical composition of claim 102, wherein the subject suffers from or is in a state of low or poor well-being, self-esteem and / or self-confidence.

117. The method of claims 87-101 show enhanced effects when the subject is treated with a combination of the said bupropion and trazodone, compared to treatment of the subject with either bupropion or trazodone alone at the same respective dosage strengths.

118. The method of claims 102-116 show enhanced effects when the subject is treated with a combination of the said bupropion and trazodone, compared to treatment of the subject with either bupropion or trazodone alone at the same respective dosage strengths.

119. The method of claims 25-87 and show enhanced effects when the subject is treated with a combination of the said bupropion and trazodone, compared to treatment of the subject with either bupropion or trazodone alone at the same respective dosage strengths.

120. A multi-function oral treatment method for treating a subject (a) who needs or desires sexual function improvement, and (b) who needs, desires or has been instructed by a health provider to lose and / or maintain weight whether or not the weight maintenance follows weight loss by the subject, said multi-function oral treatment method comprises: orally administering an effective amount of a first compound to the subject, andAttorney Docket No.49848-4040PCT orally administering an effective amount of a second compound to the subject for improving the subject’s sexual function and effecting weight loss and / or weight maintenance by the subject; wherein the said first compound is bupropion or a pharmaceutically acceptable salt thereof and the said second compound is trazodone or a pharmaceutically acceptable salt thereof; wherein the said first compound and the said second compound are formulated into dosage forms suitable for oral combination administration to the subject; wherein the oral dosage form (i) is a single combination oral dosage form comprising the said bupropion and the said trazodone, or (ii) is a first distinct, separate oral dosage form comprising the said bupropion, and a second distinct, separate oral dosage form comprising the said trazodone; wherein (1) the trazadone dosage strengths and the bupropion dosage strengths are selected from a group of combination dosage strengths consisting of (a) trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 250 mg, (b) trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 300 mg, (c) trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 250 mg, (d) trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 300 mg, (e) trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 150 mg, and (f) trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 150 mg, or (2) the bupropion is in a dosage strength range and the trazadone is in a dosage strength range selected from a group of combination dosage strength ranges consisting of (a) bupropion in a dosage strength range of 100-300 mg and trazodone in a dosage strength range of 75-150 mg, (b) comprising bupropion in a dosage strength range of 225-300 mg and comprising trazodone in a dosage strength range of 75-150 mg, (c) bupropion in a dosage strength range of 100-275 mg and comprising trazodone in a dosage strength range of 50-100 mg, and (d) bupropion in a dosage strength range of 200-275 mg and comprising trazodone in a dosage strength range of 50-100 mg;Attorney Docket No.49848-4040PCT whereby the said multi-function oral treatment method effectuates sexual function improvement and weight loss and / or weight maintenance when the bupropion and trazodone are administered orally to the subject in accordance with a treatment regimen.

121. The multi-function oral treatment method of claim 120, wherein the said oral treatment method includes the further step of: orally administering the said single, combination oral dosage form to the subject at least once daily in accordance with the treatment regimen.

122. The multi-function oral treatment method of claim 120, wherein the said oral treatment method includes the further step of: orally administering the said first distinct, separate oral dosage form and the said second distinct, separate oral dosage form to the subject concurrently, simultaneously, or sequentially.

123. The multi-function oral treatment method of claim 120, including the further step of: orally administering the said first distinct, separate oral dosage form and the said second distinct, separate oral dosage form to the subject concurrently, simultaneously, or sequentially at least once daily in accordance with the treatment regimen.

124. The multi-function oral treatment method of claim 120, wherein the said single combination oral dosage form, the said first distinct, separate oral dosage form, and the said second distinct, separate oral dosage form are solid oral dosage forms.

125. The multi-function oral treatment method of claim 124, wherein the said solid oral dosage forms are selected from a group of solid dosage forms comprising capsules, tablets, pills, dragees, powders, granules, cachets, and lozenges.Attorney Docket No.49848-4040PCT 126. The multi-function oral treatment method of claim 124, wherein the oral solid dosage forms are controlled-release, delayed-release, extended-release, modified- release, or sustained-release solid dosage form.

127. The multi-function oral treatment method of claim 126, wherein the solid oral dosage forms provide sustained delivery of the bupropion and sustained delivery of the trazodone to the subject for at least about 12 hours after the solid oral dosage forms are administered to the subject.

128. The multi-function oral treatment method of claims 120-127 show enhanced effects when the subject is treated with a combination of the said bupropion and trazodone, compared to treatment of the subject with either bupropion or trazodone alone at the same respective dosage strengths.

129. The multi-function oral treatment method of claim 120, wherein the subject loses between about 5% and 10.2% of weight when the said oral treatment method is followed by the subject in accordance with the treatment regimen.

130. The multi-function oral treatment method of claim 120, wherein the subject loses between about 5% and 10.2% of weight when the said oral treatment method is followed by the subject in accordance with the treatment regimen for at least about 4 weeks.

131. The multi-function oral treatment method of claim 120, wherein the subject is overweight.

132. The multi-function oral treatment method of claim 120, wherein the subject is obese.

133. The multi-function oral treatment method of claim 120, wherein the sexual function is a sexual disorder or sexual dysfunction (SD), and wherein the SD is selected from a group of SDs consisting of female sexual disorder (FSD), female sexual arousal disorderAttorney Docket No.49848-4040PCT (FSAD), female sexual interest / arousal disorder (FSIAD), female hypoactive sexual desire disorder (HSDD), female orgasmic disorder (FOD), female pain disorder (FPD), sexual interest arousal disorder (SIAD), male sexual disorder (MSD), male hypoactive sexual desire disorder (MSHDD), erectile dysfunction (ED), Pyronine’s disease (PD), male premature ejaculation (MPE), male delayed ejaculation (MDE), male decreased libido (MDL), male dry orgasm (MDO) and any appropriate combination.

134. The multi-function oral treatment method of claim 120, wherein the subject suffers from or is in a state of low or poor well-being, self-esteem and / or self-confidence.

135. A multi-function oral treatment method for treating a subject to improve the subject’s sexual function, to induce weight loss and / or effectuate weight maintenance by the subject, and to improve the subject’s subjective state of well-being, self-esteem and / or self-confidence, wherein the subject (a) needs or desires sexual function improvement, (b) needs or desires to lose or maintain weight, and (c) needs or desires improvement in his or her subjective state of well-being, self-esteem and / or self-confidence, said multi- function oral treatment method comprises: orally administering an effective amount of a first compound and an effective amount of a second compound to the subject who needs or desires to improve his or her sexual function, and who needs, desires or has been instructed by a health provider to lose weight; wherein the said first compound is bupropion or a pharmaceutically acceptable salt thereof and the said second compound is trazodone or a pharmaceutically acceptable salt thereof; wherein the said first compound and the said second compound are formulated as solid dosage forms suitable for oral combination administration; wherein the oral dosage form (i) is a single combination oral dosage form comprising the said bupropion and the said trazodone, or (ii) is a first distinct, separate oral dosage form comprising the said bupropion, and a second distinct, separate oral dosage form comprising the said trazodone;Attorney Docket No.49848-4040PCT wherein (1) the trazadone dosage strengths and the bupropion dosage strengths are selected from a group of combination dosage strengths consisting of (a) trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 250 mg, (b) trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 300 mg, (c) trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 250 mg, (d) trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 300 mg, (e) trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 150 mg, and (f) trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 150 mg, or (2) the bupropion is in a dosage strength range and the trazadone is in a dosage strength range selected from a group of combination dosage strength ranges consisting of (a) bupropion in a dosage strength range of 100-300 mg and trazodone in a dosage strength range of 75- 150 mg, (b) comprising bupropion in a dosage strength range of 225-300 mg and comprising trazodone in a dosage strength range of 75-150 mg, (c) bupropion in a dosage strength range of 100-275 mg and comprising trazodone in a dosage strength range of 50-100 mg, and (d) bupropion in a dosage strength range of 200-275 mg and comprising trazodone in a dosage strength range of 50-100 mg; whereby, the said multi-function combination treatment method improves sexual function, induces weight loss or maintains weight by the subject, and improves the subject’s subjective state of well-being, self-esteem and / or self-confidence, when the said multi-function oral treatment method is followed by the subject in accordance with a treatment regimen.

136. The multi-function oral treatment method of claim 135, wherein the said oral treatment method includes the further step of: orally administering the said single, combination oral dosage form to the subject at least once daily in accordance with the treatment regimen.

137. The multi-function oral treatment method of claim 135, wherein the said oral treatment method includes the further step of:Attorney Docket No.49848-4040PCT orally administering the said first distinct, separate oral dosage form and the said second distinct, separate oral dosage form to the subject concurrently, simultaneously, or sequentially.

138. The multi-function oral treatment method of claim 135, including the further step of: orally administering the said first distinct, separate oral dosage form and the said second distinct, separate oral dosage form to the subject concurrently, simultaneously, or sequentially at least once daily in accordance with the treatment regimen.

139. The multi-function oral treatment method of claim 135, wherein the said single combination oral dosage form, the said first distinct, separate oral dosage form, and the said second distinct, separate oral dosage form are solid oral dosage forms.

140. The multi-function oral treatment method of claim 139, wherein the said solid oral dosage forms are selected from a group of solid dosage forms comprising capsules, caplets, tablets, pills, dragees, powders, granules, cachets, and lozenges.

141. The multi-function oral treatment method of claim 139, wherein the oral solid dosage forms are controlled-release, delayed-release, extended-release, modified- release, or sustained-release solid dosage form.

142. The multi-function oral treatment method of claim 141, wherein the solid oral dosage forms provide sustained delivery of the bupropion and sustained delivery of the trazodone to the subject for at least about 12 hours after the solid oral dosage forms are administered to the subject.

143. The multi-function oral treatment method of claims 135-143 show enhanced effects when the subject is treated with a combination of the said bupropion and trazodone, compared to treatment of the subject with either bupropion or trazodone alone at the same respective dosage strengths.Attorney Docket No.49848-4040PCT 144. The multi-function oral treatment method of claim 135, wherein the subject loses between about 5% and 10.2% of weight when the said oral treatment method is followed by the subject in accordance with the treatment regimen.

145. The multi-function oral treatment method of claim 135, wherein the subject loses between about 5% and 10.2% of weight when the said oral treatment method is followed by the subject in accordance with the treatment regimen for at least about 4 weeks.

146. The multi-function oral treatment method of claim 135, wherein the subject is overweight.

147. The multi-function oral treatment method of claim 135, wherein the subject is obese.

148. The multi-function oral treatment method of claim 135, wherein the sexual function is a sexual disorder or sexual dysfunction (SD), and wherein the SD is selected from a group of SDs consisting of female sexual disorder (FSD), female sexual arousal disorder (FSAD), female sexual interest / arousal disorder (FSIAD), female hypoactive sexual desire disorder (HSDD), female orgasmic disorder (FOD), female pain disorder (FPD), sexual interest arousal disorder (SIAD), male sexual disorder (MSD), male hypoactive sexual desire disorder (MSHDD), erectile dysfunction (ED), Pyronine’s disease (PD), male premature ejaculation (MPE), male delayed ejaculation (MDE), male decreased libido (MDL), male dry orgasm (MDO) and any appropriate combination.

149. The multi-function oral treatment method of claim 135, wherein the subject suffers from or is in a state of low or poor well-being, self-esteem and / or self-confidence.

150. A sexual disorder or dysfunction (SD) oral treatment method for treating a subject for SD who needs or desires SD improvement, said SD oral treatment method comprises: orally administering an effective amount of a first compound to the subject, andAttorney Docket No.49848-4040PCT orally administering an effective amount of a second compound to the subject for improving the subject’s sexual function and effecting weight loss and / or weight maintenance by the subject; wherein the said first compound is bupropion or a pharmaceutically acceptable salt thereof and the said second compound is trazodone or a pharmaceutically acceptable salt thereof; wherein the said first compound and the said second compound are formulated into dosage forms suitable for oral combination administration to the subject; wherein the oral dosage form (i) is a single combination oral dosage form comprising the said bupropion and the said trazodone, or (ii) is a first distinct, separate oral dosage form comprising the said bupropion, and a second distinct, separate oral dosage form comprising the said trazodone; wherein (1) the trazadone dosage strengths and the bupropion dosage strengths are selected from a group of combination dosage strengths consisting of (a) trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 250 mg, (b) trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 300 mg, (c) trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 250 mg, (d) trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 300 mg, (e) trazodone is in a dosage strength of about 75 mg and the bupropion is in a dosage strength of about 150 mg, and (f) trazodone is in a dosage strength of about 150 mg and the bupropion is in a dosage strength of about 150 mg, or (2) the bupropion is in a dosage strength range and the trazadone is in a dosage strength range selected from a group of combination dosage strength ranges consisting of (a) bupropion in a dosage strength range of 100-300 mg and trazodone in a dosage strength range of 75-150 mg, (b) comprising bupropion in a dosage strength range of 225-300 mg and comprising trazodone in a dosage strength range of 75-150 mg, (c) bupropion in a dosage strength range of 100-275 mg and comprising trazodone in a dosage strength range of 50-100 mg, and (d) bupropion in a dosage strength range of 200-275 mg and comprising trazodone in a dosage strength range of 50-100 mg;Attorney Docket No.49848-4040PCT wherein the SD is selected from a group of SDs consisting of female sexual disorder (FSD), female sexual arousal disorder (FSAD), female sexual interest / arousal disorder (FSIAD), female hypoactive sexual desire disorder (HSDD), female orgasmic disorder (FOD), female pain disorder (FPD), sexual interest arousal disorder (SIAD), male sexual disorder (MSD), male hypoactive sexual desire disorder (MSHDD), erectile dysfunction (ED), Pyronine’s disease (PD), male premature ejaculation (MPE), male delayed ejaculation (MDE), male decreased libido (MDL), male dry orgasm (MDO) and any appropriate combination; whereby the said SD oral treatment method effectuates subject sexual function improvement when the said bupropion and the said trazodone are administered orally to the subject in accordance with a treatment regimen.

151. The SD oral treatment method of claim 150, wherein the said oral treatment method includes the further step of: orally administering the said single, combination oral dosage form to the subject at least once daily in accordance with the treatment regimen.

152. The SD oral treatment method of claim 150, wherein the said oral treatment method includes the further step of: orally administering the said first distinct, separate oral dosage form and the said second distinct, separate oral dosage form to the subject concurrently, simultaneously, or sequentially.

153. The SD oral treatment method of claim 150, including the further step of: orally administering the said first distinct, separate oral dosage form and the said second distinct, separate oral dosage form to the subject concurrently, simultaneously, or sequentially at least once daily in accordance with the treatment regimen.

154. The SD oral treatment method of claim 150, wherein the said single combination oral dosage form, the said first distinct, separate oral dosage form, and the said second distinct, separate oral dosage form are solid oral dosage forms.Attorney Docket No.49848-4040PCT 155. The SD oral treatment method of claim 154, wherein the said solid oral dosage forms are selected from a group of solid dosage forms comprising capsules, tablets, pills, dragees, powders, granules, cachets, and lozenges.

156. The SD oral treatment method of claim 154, wherein the oral solid dosage forms are controlled-release, delayed-release, extended-release, modified-release, or sustained-release solid dosage form.

157. The SD oral treatment method of claim 156, wherein the solid oral dosage forms provide sustained delivery of the bupropion and sustained delivery of the trazodone to the subject for at least about 12 hours after the solid oral dosage forms are administered to the subject.

158. The SD oral treatment method of claims 135-157 show enhanced effects when the subject is treated with a combination of the said bupropion and trazodone, compared to treatment of the subject with either bupropion or trazodone alone at the same respective dosage strengths.

159. The SD oral treatment method of claim 135, wherein the subject is overweight.

160. The SD oral treatment method of claim 135, wherein the subject is obese.

161. The SD oral treatment method of claim 135, wherein the subject suffers from or is in a state of low or poor well-being, self-esteem and / or self-confidence.