How to Treat the Symptoms of Autism Spectrum Disorder

Abstract

Provided herein are methods for treating symptoms associated with autism spectrum disorder (ASD) by administering a therapeutically effective amount of a triptan.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent Application No. 62 / 925,023, filed October 23, 2019, and U.S. Provisional Patent Application No. 63 / 011,715, filed April 17, 2020, the contents of which are hereby incorporated by reference in their entirety for all purposes. [Background technology]

[0002] background

[0002] Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder characterized by stereotyped behaviors and deficits in language and social interaction. As of 2014, the reported incidence of autism in the United States has skyrocketed to 1 in 59 newborns (https: / / www.cdc.gov / mmwr / volumes / 67 / ss / ss6706a1.htm), posing a significant medical and societal burden in the coming decades. To date, there are no FDA-approved treatments for reducing or eliminating the core symptoms of autism spectrum disorder. There is a need in the art for methods to treat symptoms associated with autism spectrum disorder, including increased irritability and impaired sociability, as well as to reduce their severity and incidence. Summary of the Invention [Means for solving the problem]

[0003] overview

[0003] In some embodiments, the present disclosure provides a method for treating symptoms associated with autism spectrum disorder (ASD), comprising administering a therapeutically effective amount of a triptan to a patient in need thereof.

[0004]

[0004] In some embodiments, the present disclosure provides a method for treating symptoms associated with ASD, comprising administering a therapeutically effective amount of zolmitriptan or a pharmaceutically acceptable salt thereof to a patient in need thereof.

[0005]

[0005] In some embodiments, the present disclosure provides a method for treating symptoms associated with ASD, comprising administering a therapeutically effective amount of sumatriptan or a pharmaceutically acceptable salt thereof to a patient in need thereof.

[0006]

[0006] In some embodiments, the present disclosure provides a method for treating symptoms associated with ASD, comprising administering a therapeutically effective amount of a triptan to a patient in need thereof, wherein after said treatment, the patient experiences a substantial improvement in sociality compared to before said treatment.

[0007] In some embodiments, the present disclosure provides a method of treating a symptom associated with ASD, the method comprising administering a therapeutically effective amount of a triptan to a patient in need thereof, wherein after said treatment, the patient experiences a substantial decrease in irritability associated with ASD compared to before said treatment. In some embodiments, the present disclosure provides a method of treating aggression associated with autism spectrum disorder (ASD), the method comprising administering a therapeutically effective amount of a triptan to a patient in need thereof, wherein after said treatment, the patient experiences a substantial decrease in aggression associated with ASD compared to before said treatment. [Brief explanation of the drawings]

[0008] BRIEF DESCRIPTION OF THE DRAWINGS [Figure 1]

[0008] Figure 1 shows the frequency of attacks in BALB / c resident mouse cages from a crossover resident-intruder (RI) study in which resident BALB / c mice were treated with vehicle control followed by treatment with 3 or 10 mg / kg zolmitriptan. [Figure 2]

[0009] Shown are aggression latencies (seconds) in BALB / c resident mouse cages from a crossover resident-intruder (RI) study in which resident BALB / c mice were treated with vehicle control followed by treatment with 3 or 10 mg / kg zolmitriptan. [Figure 3]

[0010] Figure 1 shows the attack latency (seconds) of adult male CD-1 mice from a crossover resident-intruder (RI) study in which resident CD-1 mice were treated with vehicle control, 10 mg / kg zolmitriptan, or 0.03 mg / kg risperidone. Attack latency was measured over a 5-minute period in a crossover design. Data are presented as the mean ± standard error of the mean. [Figure 4]

[0011] Figure 1 shows social index in a valproic acid (VPA)-induced autism spectrum disorder c57 / B16 mouse model in mice treated with vehicle control or 10 mg / kg zolmitriptan. [Figure 5]

[0012] 1 shows the mean CSF levels of zolmitriptan and its metabolite N-desmethylzolmitriptan (NDMZ) following oral administration of 5 mg, 10 mg, 20 mg, and 30 mg doses to human subjects. DETAILED DESCRIPTION OF THE INVENTION

[0009] definition

[0013] Throughout this disclosure, various patents, patent applications, and publications (including non-patent publications) are referenced. The disclosures of these patents, patent applications, and publications are incorporated by reference in their entireties into this disclosure for all purposes to more fully describe the state of the art as known to those skilled in the art as of the date of this disclosure. In the event of any conflict between the cited patents, patent applications, and publications and this disclosure, the present disclosure shall control.

[0010]

[0014] For convenience, certain terms employed in the specification, examples, and claims are collected here. Unless otherwise defined, all technical and scientific terms used in this disclosure have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0011]

[0015] The term "about," when placed immediately before a numerical value, denotes a range (e.g., ±10% of that value). For example, unless the context of this disclosure dictates otherwise or contradicts such an interpretation, "about 50" can mean 45 to 55, "about 25,000" can mean 22,500 to 27,500, etc. For example, in a list of numerical values ​​such as "about 49, about 50, about 55, ...," "about 50" denotes a range extending to less than half of one or more intervals between the preceding and following values, e.g., a range greater than 49.5 and less than 52.5. Furthermore, the phrases "less than about (a value)" or "greater than about (a value)" should be understood in light of the definition of the term "about" provided herein. Similarly, the term "about," when placed before a series of numerical values ​​or range of values ​​(e.g., "about 10, 20, 30" or "about 10 to 30"), refers to every value in that series or to each of the endpoints of that range.

[0012]

[0016] The terms "administer," "administering," or "administration," as used herein, refer to either administering a compound or a pharmaceutically acceptable salt or ester of the compound, or a composition comprising the compound or a pharmaceutically acceptable salt or ester of the compound, directly to a patient.

[0013]

[0017] The terms "effective amount" and "therapeutically effective amount" are used interchangeably in this disclosure and refer to an amount of a compound, or a salt, solvate, or ester thereof, capable of achieving an intended result when administered to a patient. For example, an effective amount of a triptan is the amount needed to reduce at least one symptom of ASD in a patient, such as the amount needed to improve irritability associated with ASD, reduce aggression associated with ASD, or increase socialization in a patient. The actual amount, including an "effective amount" or "therapeutically effective amount," will vary depending on several factors, including, but not limited to, the triptan administered, the severity of the disorder, the size and health of the patient, and the route of administration. A skilled physician can readily determine the appropriate amount using the methods described herein and as known in the medical arts.

[0014]

[0018] The phrase "pharmaceutically acceptable," as used herein, refers to compounds, materials, compositions, and / or dosage forms that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without undue toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit-risk ratio.

[0015]

[0019] The term "salts" as used herein encompasses pharmaceutically acceptable salts commonly used to form alkali metal salts of free acids and addition salts of free bases. The nature of the salt is not critical, provided it is pharmaceutically acceptable. The term "salts" also includes solvates of addition salts, such as hydrates, as well as polymorphs of addition salts. Suitable pharmaceutically acceptable acid addition salts can be prepared from inorganic acids or organic acids. Examples of such inorganic acids are hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, carbonic acid, sulfuric acid, and phosphoric acid. Suitable organic acids may be selected from aliphatic, alicyclic, aromatic, arylaliphatic, and heterocyclyl containing carboxylic and sulfonic acids, such as formic acid, acetic acid, propionic acid, succinic acid, glycolic acid, gluconic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, glucuronic acid, maleic acid, fumaric acid, pyruvic acid, aspartic acid, glutamic acid, benzoic acid, anthranilic acid, mesylic acid, stearic acid, salicylic acid, p-hydroxybenzoic acid, phenylacetic acid, mandelic acid, embonic acid (pamoic acid), methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, pantothenic acid, toluenesulfonic acid, 2-hydroxyethanesulfonic acid, sulfanilic acid, cyclohexylaminosulfonic acid, algenic acid, 3-hydroxybutyric acid, galactaric acid, and galacturonic acid.

[0016]

[0020] The term "treating," as used herein with reference to a patient, refers to improving at least one symptom of the patient's disorder. Treating can be improving or at least partially reversing the disorder. For example, a patient's autism spectrum disorder is treated when the method reduces at least one symptom of the patient's ASD, such as irritability, aggression, or social impairment.

[0017]

[0021] The term "therapeutic effect" as used herein refers to a desired or beneficial effect provided by the method and / or composition. For example, a method of treating autism spectrum disorder provides a therapeutic effect if the method improves at least one symptom of ASD in a patient, such as, for example, improvement in ASD-associated irritability, improvement in ASD-associated aggression, or increased sociability.

[0018] Detailed Description of the Invention

[0022] Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction and communication, restricted interests, and repetitive behaviors. The degree and type of impairments seen in individuals with autism spectrum disorder vary widely, ranging from mild to severe. Early detection and intervention are encouraged to maximize benefits and reduce the severity of symptoms, but interventions and therapies that can reduce symptoms and enhance skills and abilities can be beneficial for individuals of any age. Suitable subjects for the methods described herein include, without limitation, humans diagnosed with or suspected of having autism spectrum disorder.

[0019]

[0023] In one aspect, the present disclosure provides a method of treating one or more symptoms of ASD by administering a therapeutically effective amount of a triptan to a patient in need thereof.

[0020]

[0024] In some embodiments, the present disclosure provides methods of treating symptoms of a condition selected from Asperger's disorder or pervasive developmental disorder not otherwise specified (PDD-NOS) by administering a therapeutically effective amount of a triptan to a patient in need thereof.

[0021]

[0025] In some embodiments, the present disclosure provides a method for improving one or more symptoms associated with ASD by administering a therapeutically effective amount of a triptan to a patient in need thereof.In some embodiments, the method of the present disclosure results in an improvement in sociality compared to before treatment.In some embodiments, the method of the present disclosure results in a reduction in irritability associated with ASD compared to before treatment.In some embodiments, the method of the present disclosure results in a reduction in aggression associated with ASD compared to before treatment.

[0022] Triptans

[0026] The triptan used in the present method may be part of a pharmaceutical composition by combining the triptan, or a pharmaceutically acceptable salt thereof, with a pharmaceutically acceptable carrier. In addition, the composition may include an additive selected from the group consisting of an adjuvant, an excipient, a diluent, a release modifier, and a stabilizer. The composition may be an immediate-release formulation, a delayed-release formulation, a sustained-release formulation, or a sustained-release formulation.

[0023]

[0027] Triptans belong to a class of serotonin receptor subtype-selective drugs. They act on the 5-HT (5-HT) receptor subtype, which belongs to the serotonin (5-HT) system. 1B , 5-HT 1D , and 5-HT 1F Triptans have selective activity against the 5-HT receptor. Triptans exhibit vasoconstrictor properties, which are due to the suppression of 5-HT receptors in arterial smooth muscle. 1B Triptan-induced vasoconstriction leads to a dose-dependent increase in blood flow velocity in the middle and large cerebral vessels. Triptans are thought to inhibit the abnormal activation of peripheral nociceptors. Triptans are presumed to reduce plasma protein extravasation (PPE) by inhibiting nociceptor activation and preventing the peripheral release of vasoactive peptides, including substance P and calcitonin gene-related peptide (CGRP). Triptan binding sites are also present in the central nervous system. Therefore, triptans may exert effects on the central nervous system. As of the time of this disclosure, triptans are FDA-approved for the treatment of migraine.

[0024]

[0028] The serotonergic system has been implicated in the pathophysiology of autism since abnormal blood 5-HT levels were identified as the first biomarker of this disorder over 50 years ago (Schain et al. J Pediatr. 1961 Mar;58:315-20). The primary source of 5-HT in the brain originates in the midbrain dorsal raphe nucleus (DRN), which projects extensively across the cortex, amygdala, and hypothalamus to other subcortical structures involved in emotional processing and social behavior. Dense serotonergic projections from the DRN innervate the nucleus accumbens (NAc), a well-conserved basal forebrain structure that acts as an integrator of motivational signals preceding the selection of behavioral actions (Kravitz et al. Physiology (Bethesda). 2012 Jun;27(3):167-77). In the context of social interactions, reward processing in the NAc is thought to govern the choice between social approach and social avoidance behaviors (Pfaff. Trends Neurosci. 2019 Jul;42(7):448-457.). Preclinical evidence supports the crucial role of 5-HT signaling in social behavior and social reward (Kane et al. PLoS One. 2012;7(11):e48975.; Challis et al. J Neurosci. 2013 Aug 28;33(35):13978-88, 13988a.; Li et al. Nat Commun. 2016 Jan 28;7:10503.). Furthermore, abnormal reward processing in the NAc has been observed in fMRI imaging studies of children with ASD (Clements et al. JAMA Psychiatry. 2018 Aug 1;75(8):797-808. doi: 10.1001 / jamapsychiatry.2018.1100.).

[0025]

[0029] In the human brain, 5-HT1B is highly expressed in the NAc (Garcia-Alloza et al. Neuropsychologia. 2005;43(3):442-9; Varnas et al. Hum Brain Mapp. 2004 Jul;22(3):246-60; Varnas et al. Synapse. 56: 21-8). It is an inhibitory G protein-coupled receptor localized to axon terminals and functions to suppress neurotransmitter release (Sari. Neurosci Biobehav Rev. 2004 Oct;28(6):565-82). As an autoreceptor, 5-HT1B inhibits the release of 5-HT, but it also plays an important role as a heteroreceptor, inhibiting the release of other neurotransmitters, including glutamate, GABA, dopamine, and acetylcholine (Boscher et al. (1994) Neuroscience 58:167-182.). According to the present disclosure, the 5-HT1B agonistic properties of the triptans described herein modulate the behavioral symptoms of ASD.

[0026]

[0030] In some embodiments, the triptan used in the formulations and methods of the present disclosure is selected from the group consisting of sumatriptan, zolmitriptan, naratriptan, rizatriptan, almotriptan, frovatriptan, eletriptan, donitriptan, avitriptan, or a pharmaceutically acceptable salt thereof.

[0027]

[0031] In some embodiments, the triptan used in the disclosed formulations and methods is sumatriptan or a pharmaceutically acceptable salt thereof. In some embodiments, the triptan used in the disclosed formulations and methods is sumatriptan hydrochloride. In some embodiments, the triptan used in the disclosed formulations and methods is sumatriptan succinate.

[0028]

[0032] In some embodiments, the methods of the present disclosure comprise administering to a patient in need thereof a therapeutically effective amount of zolmitriptan or a pharmaceutically acceptable salt thereof.

[0029]

[0033] In some embodiments, the methods of the present disclosure comprise administering to a patient in need thereof a therapeutically effective amount of naratriptan or a pharmaceutically acceptable salt thereof, in some embodiments, the pharmaceutically acceptable salt is naratriptan hydrochloride.

[0030]

[0034] In some embodiments, the methods of the present disclosure comprise administering to a patient in need thereof a therapeutically effective amount of rizatriptan or a pharmaceutically acceptable salt thereof, in some embodiments, the pharmaceutically acceptable salt is rizatriptan benzoate.

[0031]

[0035] In some embodiments, the methods of the present disclosure comprise administering a therapeutically effective amount of almotriptan or a pharmaceutically acceptable salt thereof to a patient in need thereof.

[0032]

[0036] In some embodiments, the methods of the present disclosure comprise administering a therapeutically effective amount of frovatriptan or a pharmaceutically acceptable salt thereof to a patient in need thereof.

[0033]

[0037] In some embodiments, the methods of the present disclosure comprise administering to a patient in need thereof a therapeutically effective amount of eletriptan or a pharmaceutically acceptable salt thereof, in some embodiments, the pharmaceutically acceptable salt is eletriptan hydrobromide.

[0034] formulation

[0038] The methods of the present disclosure can employ a variety of pharmaceutical compositions in unit dosage forms, such as tablets, capsules, pills, powders, granules, sterile parenteral solutions or suspensions, inhalable dry powders, dispersions, solutions or suspensions, and oral solutions or suspensions, and oil-in-water emulsions, containing a suitable amount of a triptan, or a pharmaceutically acceptable salt thereof, for administration to patients, e.g., humans and animals.

[0035]

[0039] In some embodiments, the pharmaceutical compositions of the present disclosure are prepared for oral administration. In some embodiments, the pharmaceutical compositions are formulated by combining one or more triptans with a pharmaceutically acceptable carrier. Some of these carriers allow the pharmaceutical compositions to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions, etc. for oral ingestion by a subject. Suitable excipients include, but are not limited to, sugars, including lactose, sucrose, mannitol, or sorbitol; modified celluloses, such as corn starch, wheat starch, rice starch, potato starch, gelatin, tragacanth gum, methylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, etc., and / or fillers such as polyvinylpyrrolidone (PVP). In certain embodiments, the mixture is optionally milled, and auxiliary agents are optionally added. In certain embodiments, the pharmaceutical composition is formed to obtain tablets or dragee cores. In certain embodiments, disintegrating agents are added, such as cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate.

[0036]

[0040] Aqueous carriers suitable for use in the present disclosure include, but are not limited to, water, ethanol, alcoholic / aqueous solutions, glycerol, emulsions or suspensions, including saline and buffered media. Oral carriers can be elixirs, syrups, capsules, tablets, and the like.

[0037]

[0041] Liquid carriers suitable for use in the present disclosure can be used to prepare solutions, suspensions, emulsions, syrups, and elixirs. The triptan can be dissolved or suspended in a pharmaceutically acceptable liquid carrier, such as water, an organic solvent, a mixture of both, or a pharmaceutically acceptable oil or fat. The liquid carrier can contain other suitable pharmaceutical additives, such as solubilizers, emulsifiers, buffers, preservatives, sweeteners, flavorings, suspending agents, thickeners, colorants, viscosity regulators, stabilizers, or osmotic pressure regulators.

[0038]

[0042] Liquid carriers suitable for use herein include, but are not limited to, water (partially containing additives as described above, such as cellulose derivatives, preferably sodium carboxymethylcellulose solution), alcohols (including monohydric and polyhydric alcohols, such as glycols) and their derivatives, and oils (e.g., fractionated coconut oil and peanut oil).

[0039]

[0043] In some embodiments, the pharmaceutical compositions of the present disclosure are prepared for administration by injection (e.g., intravenous, subcutaneous, intramuscular, etc.). In some such embodiments, the pharmaceutical composition comprises a carrier and is formulated in an aqueous solution such as water or a physiologically compatible buffer, e.g., Hank's solution, Ringer's solution, or physiological saline buffer. In certain embodiments, other ingredients (e.g., ingredients that aid in solubility or act as preservatives) are included. In certain embodiments, injectable suspensions are prepared using appropriate liquid carriers, suspending agents, etc. Some injectable pharmaceutical compositions are provided in unit dosage form, e.g., in ampoules or multi-dose containers. Some injectable pharmaceutical compositions are suspensions, solutions, or emulsions in oily or aqueous vehicles and may contain formulatory agents such as suspending agents, stabilizing agents, and / or dispersing agents. Certain solvents suitable for use in injectable pharmaceutical compositions include, but are not limited to, lipophilic solvents such as sesame oil and fatty oils, synthetic fatty acid esters such as ethyl oleate or triglycerides, and liposomes. Aqueous injection suspensions may contain substances which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, such suspensions may also contain suitable stabilizers or agents which increase the solubility of the drugs, to allow for the preparation of highly concentrated solutions.

[0040]

[0044] Sterile injectable preparations may also be sterile injectable solutions or suspensions in non-toxic, parenterally acceptable diluents or solvents, such as a solution in 1,3-butanediol, or may be prepared as lyophilized powders. Among the acceptable vehicles and solvents that may be used are water, Ringer's solution, and isotonic saline. Additionally, sterile, fixed oils are conventionally used as solvents or suspending media. For this purpose, any bland fixed oil can be used, including synthetic mono- or diglycerides. Additionally, fatty acids, such as oleic acid, can also be used to prepare injectable solutions. Intravenous formulations may include solutions in sterile, isotonic aqueous buffer. Where necessary, the formulation may also include a solubilizing agent and a local anesthetic to ease pain at the injection site. Generally, these ingredients are supplied separately or mixed together in a unit dosage form, for example, as a dry, lyophilized powder or waterless concentrate in a hermetically sealed container, such as an ampoule or sachet, indicating the quantity of active agent. Where the compound is to be administered by infusion, the compound in the formulation may be dispensed with an infusion bottle containing sterile pharmaceutical grade water, saline, or dextrose / water. Where the compound is administered by injection, an ampoule of sterile water for injection or saline may be provided so that the ingredients can be mixed prior to administration.

[0041]

[0045] Suitable formulations further include aqueous and non-aqueous sterile injection solutions which may contain antioxidants, buffers, bacteriostats, bactericidal antibiotics and solutes which render the formulation isotonic with the body fluids of the intended recipient; and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents.

[0042]

[0046] In certain embodiments, the pharmaceutical composition of the present disclosure is formulated as a depot preparation.Some of these depot preparations are typically longer-acting than non-depot preparations.In certain embodiments, these preparations are administered by implantation (for example, subcutaneously or intramuscularly) or intramuscular injection.In certain embodiments, depot preparations are prepared using suitable polymers or hydrophobic materials (for example, emulsions in acceptable oils) or ion exchange resins, or as sparingly soluble derivatives, for example, as sparingly soluble salts.

[0043]

[0047] In some embodiments, the pharmaceutical compositions of the present disclosure are formulated for intranasal administration.

[0044] Administration and Dosage

[0048] The present disclosure provides methods for treating symptoms associated with autism spectrum disorder (ASD) by administering an effective amount of a triptan or a pharmaceutically acceptable salt thereof to a patient in need thereof. In some embodiments, the effective amount is an amount sufficient to eliminate or significantly reduce one or more symptoms associated with ASD, or to alleviate those symptoms (e.g., reduce symptoms such as irritability, aggression, or improve socialization compared to symptoms observed before treatment). In some embodiments, the effective amount is an amount sufficient to eliminate or significantly reduce irritability associated with ASD compared to before treatment. In some embodiments, the effective amount is an amount sufficient to eliminate or significantly improve socialization compared to before treatment.

[0045]

[0049] The reduction of autism symptoms in ASD patients can be determined by various methods. In some embodiments, the effectiveness of dosage regimen can be determined by assessment according to OSU Autism Rating Scale (OARS-5), Vineland Adaptive Behavior Scales, ADOS-2, CGI-S and CGI-C Social Deficit Subscale, Autism Behavior Inventory, and Childhood Autism Rating Scale, Interpersonal Responsiveness Scale, Aberrant Behavior Checklist, Social Development Disorders Behavior Inventory, Top 3 Caregiver Concerns, Autism Behavior Inventory, and Autism Treatment Evaluation Checklist (ATEC), Interpersonal Responsiveness Scale-2 (SRS-2), or any combination thereof.

[0046]

[0050] According to some embodiments of the present disclosure, the administration frequency and dosage per administration of the triptan are selected to provide a therapeutic effect for the treatment of one or more symptoms associated with ASD.

[0047]

[0051] In some embodiments, the dosing frequency and dosage per administration of the triptan are selected to provide a therapeutic effect for treating irritability symptoms associated with ASD.

[0048]

[0052] In some embodiments, the dosing frequency and dosage per administration of the triptan are selected to provide a therapeutic effect for treating aggressive symptoms associated with ASD.

[0049]

[0053] In some embodiments, the dosing frequency and dosage per administration of the triptan are selected to provide a therapeutic effect for treating social symptoms associated with ASD.

[0050]

[0054] In some embodiments, the disclosed methods for treating symptoms associated with autism include administering a therapeutically effective amount of sumatriptan or a pharmaceutically acceptable salt thereof to a patient in need thereof. In some embodiments, the methods ... This involves administering to a patient in need thereof about 1 mg to about 200 mg (including all values ​​and ranges therebetween) of sumatriptan or a pharmaceutically acceptable salt thereof, including about 90 mg, about 95 mg, and about 100 mg, about 105 mg, about 110.0 mg, about 115 mg, about 120 mg, about 125 mg, about 130 mg, about 135 mg, about 140 mg, about 145 mg, about 150 mg, about 155 mg, about 160 mg, about 165 mg, about 170 mg, about 175 mg, about 180 mg, about 185 mg, about 190 mg, about 195 mg, and about 200 mg. In some embodiments, about 25 mg to about 200 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 25 mg to about 100 mg of sumatriptan or a pharmaceutically acceptable salt is administered to a patient in need thereof.

[0051]

[0055] In some embodiments, the methods of the disclosure provide a method for administering a therapeutically effective amount of a medicament for the treatment of a patient with ... mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, about 100 mg, about 105 mg, about 110.0 mg, about 115 mg, about 120 mg, about 125 mg, about 130 mg, about 135 mg, about 140 mg, about 145 mg, about 150 mg, about 155 mg, about 160 mg, about 165 mg, about 170 mg, about 175 mg, about 180 mg, about 185 mg, about 190 mg, about 195 mg, or about 200 mg of sumatriptan or a pharmaceutically acceptable salt thereof to a patient in need thereof.

[0052]

[0056] In some embodiments, about 3 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 6 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 5 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 10 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 20 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof.

[0053]

[0057] In some embodiments, sumatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, sumatriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, sumatriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0054]

[0058] In some embodiments, about 3 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 3 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 3 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered three times daily. In some embodiments, about 3 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered four times daily.

[0055]

[0059] In some embodiments, about 6 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 6 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered twice daily.

[0056]

[0060] In some embodiments, about 5 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 5 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered twice daily.

[0057]

[0061] In some embodiments, about 10 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 10 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 10 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0058]

[0062] In some embodiments, about 20 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 20 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 20 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0059]

[0063] In some embodiments, about 22 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 22 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 22 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0060]

[0064] In some embodiments, about 25 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 25 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 25 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0061]

[0065] In some embodiments, about 50 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 50 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 50 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0062]

[0066] In some embodiments, about 100 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 100 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 100 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0063]

[0067] In some embodiments, the methods of the present disclosure result in plasma levels of sumatriptan (e.g., mean steady-state plasma levels) that correlate with one or more statistically significant therapeutic effects. In some embodiments, therapeutically effective plasma levels of sumatriptan resulting from the methods of the present disclosure are about 10 ng / ml, about 20 ng / ml, about 30 ng / ml, about 40 ng / ml, about 50 ng / ml, about 60 ng / ml, about 70 ng / ml, about 80 ng / ml, about 90 ng / ml, about 100 ng / ml, about 110 ng / ml, about 120 ng / ml, about 130 ng / ml, about 140 ng / ml, about 150 ng / ml, about 160 ng / ml, about 170 ng / ml, about 180 ng / ml, about 190 ng / ml, about 210 ng / ml, about 220 ng / ml, about 230 ng / ml, about 240 ng / ml, about 250 ng / ml, about 260 ng / ml, about 270 ng / ml, about 280 ng / ml, about 290 ng / ml, about 300 ng / ml, about 310 ng / ml, about 320 ng / ml, about 330 ng / ml, about 340 ng / ml, about 350 ng / ml, about 360 ng / ml, about 370 ng / ml, about 380 ng / ml, about 390 ng / ml, about 400 ng / ml, about 410 ng / ml, about 420 ng / ml, about 430 ng / ml, about 440 ng / ml, about 450 ng / ml, about 460 ng / ml, about The range is from about 10 ng / mL to about 300 ng / mL (including all values ​​and ranges therebetween), including about 170 ng / mL, about 180 ng / mL, about 190 ng / mL, about 200 ng / mL, about 210 ng / mL, about 220 ng / mL, about 230 ng / mL, about 240 ng / mL, about 250 ng / mL, about 260 ng / mL, about 270 ng / mL, about 280 ng / mL, about 290 ng / mL, and about 300 ng / mL.

[0064]

[0068] In some embodiments, the disclosed methods result in a plasma Cmax of sumatriptan of about 10 ng / mL to about 150 ng / mL (including all values ​​and ranges therebetween), including about 10 ng / mL, about 20 ng / mL, about 30 ng / mL, about 40 ng / mL, about 50 ng / mL, about 60 ng / mL, about 70 ng / mL, about 80 ng / mL, about 90 ng / mL, about 100 ng / mL, about 110 ng / mL, about 120 ng / mL, about 130 ng / mL, about 140 ng / mL, and about 150 ng / mL. In some embodiments, the disclosed methods result in a plasma Cmax of sumatriptan of about 10 ng / mL to about 100 ng / mL.

[0065]

[0069] In some embodiments, the disclosed methods for treating symptoms associated with autism include administering a therapeutically effective amount of zolmitriptan or a pharmaceutically acceptable salt thereof to a patient in need thereof. In some embodiments, the methods include administering a therapeutically effective amount of about 1.0 mg, about 1.25 mg, about 1.5 mg, about 1.75 mg, about 2.0 mg, about 2.25 mg, about 2.5 mg, about 3.0 mg, about 3.5 mg, about 4.0 mg, about 4.5 mg, about 5.0 mg, about 5.5 mg, about 6.0 mg, about 6.5 mg, about 7.0 mg, about 7.5 mg, about 8.0 mg, about 8.5 mg, about 9.0 mg, about 9.5 mg, about 10.0 mg, about 10.5 mg, about 11.0 mg, about 11.5 mg, about 12.0 mg, about 12.5 mg, about 13.0 mg, about 13.5 mg, about 14.0 mg, about 14.5 mg, about 15.0 mg, about 15.5 mg, about 16.0 mg, about 16.5 mg, about 17.0 mg, about 17.5 mg, about 18.0 mg, about 18.5 mg, about 19.0 mg, about 19.5 mg, about 20.0 mg, about 20.5 mg, about 21.0 mg, about 21.5 mg, about 22.0 mg, about 22.5 mg, about 23.0 mg, about 23.5 mg, about 24.0 mg, about 24.5 mg, about 25.0 mg, about 25.5 mg, about 26.0 mg, about 26.5 mg, about 27.0 mg, about 27.5 mg, about 28.0 mg, about 28.5 mg 3.0mg, about 13.5mg, about 14.0mg, about 14.5mg, about 15.0mg, about 15.5mg, about 16.0mg, about 16.5mg, about 17.0mg, about 17.5mg, about 18.0mg, about 18.5mg, about 19.0mg, about 19.5mg, about 20.0mg, about 20.5mg, about 21.0mg, about 21.5mg, about 22.0mg, about 22.5mg, about 23.0mg, about 23.5mg, about 24.0mg, about 24.5mg, about 25.0mg, about 25.5mg, about 26.0mg, about 2 6.5mg, about 27.0mg, about 27.5mg, about 28.0mg, about 28.5mg, about 29.0mg, about 29.5mg, about 30.0mg, about 30.5mg, about 31mg, about 31.5mg, about 32mg, about 32.5mg, about 33mg, about 33. 5mg, about 34mg, about 34.5mg, about 35mg, about 35.5mg, about 36mg, about 36.5mg, about 37mg, about 37.5mg, about 38mg, about 38.5mg, about 39mg, about 39.5mg, about 40mg, about 40.5mg, about 41mg, It involves administering to a patient in need thereof about 1.0 mg to about 50 mg (including all values ​​and ranges therebetween) of zolmitriptan or a pharmaceutically acceptable salt thereof, including about 41.5 mg, about 42 mg, about 42.5 mg, about 43 mg, about 43.5 mg, about 44 mg, about 44.5 mg, about 45.0 mg, about 45.5 mg, about 46 mg, about 46.5 mg, about 47 mg, about 47.5 mg, about 48 mg, about 48.5 mg, about 49.0 mg, about 49.5 mg, and about 50 mg.In some embodiments, about 1.25 mg to about 35 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 1.7 mg to about 30 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, the methods of the present disclosure provide a method for administering a dose of about 1.0 mg, about 1.25 mg, about 1.5 mg, about 1.75 mg, about 2.0 mg, about 2.25 mg, about 2.5 mg, about 3.0 mg, about 3.5 mg, about 4.0 mg, about 4.5 mg, about 5.0 mg, about 5.5 mg, about 6.0 mg, about 6.5 mg, about 7.0 mg, about 7.5 mg, about 8.0 mg, about 8.5 mg, about 9.0 mg, about 9.5 mg, about 10.0 mg, about 10.5 mg, about 11.0 mg, about 11.5 mg, about 12.0 mg, about 13.0 mg, about 14.0 mg, about 15.0 mg, about 16.0 mg, about 17.0 mg, about 18.0 mg, about 19.0 mg, about 20.0 mg, about 21.0 mg, about 22.0 mg, about 23.0 mg, about 24.0 mg, about 25.0 mg, about 26.0 mg, about 27.0 mg, about 28.0 mg, about 29.0 mg, about 30.0 mg, about 31.0 mg, about 32.0 mg, about 33.0 mg, about 34.0 mg, about 35.0 mg, about 36.0 mg, about 37.0 mg, about 38.0 mg, about 39.0 mg, about 39.5 mg, about mg, about 12.5 mg, about 13.0 mg, about 13.5 mg, about 14.0 mg, about 14.5 mg, about 15.0 mg, about 15.5 mg, about 16.0 mg, about 16.5 mg, about 17.0 mg, about 17.5 mg, about 18.0 mg, about 18.5 mg, about 19.0mg, about 19.5mg, about 20.0mg, about 20.5mg, about 21.0mg, about 21.5mg, about 22.0mg, about 22.5mg, about 23.0mg, about 23.5mg, about 24.0mg, about 24.5mg, about 25.0 mg, about 25.5mg, about 26.0mg, about 26.5mg, about 27.0mg, about 27.5mg, about 28.0mg, about 28.5mg, about 29.0mg, about 29.5mg, about 30.0mg, about 30.5mg, about 31mg, about 31.5m g, about 32mg, about 32.5mg, about 33mg, about 33.5mg, about 34mg, about 34.5mg, about 35mg, about 35.5mg, about 36mg, about 36.5mg, about 37mg, about 37.5mg, about 38mg, about 38.5mg, about 39m g, about 39.5 mg, about 40 mg, about 40.5 mg, about 41 mg, about 41.5 mg, about 42 mg, about 42.5 mg, about 43 mg, about 43.5 mg, about 44 mg, about 44.5 mg, about 45.0 mg, about 45.5 mg, about 46 mg, about 46.5 mg, about 47 mg, about 47.5 mg, about 48 mg, about 48.5 mg, about 49.0 mg, about 49.5 mg, or about 50 mg of zolmitriptan or a pharmaceutically acceptable salt thereof to a patient in need thereof.

[0066]

[0070] In some embodiments, about 2.0 mg to about 15 mg (including all values ​​and ranges therebetween) of zolmitriptan or a pharmaceutically acceptable salt, including about 1.0 mg, about 1.5 mg, about 2.0 mg, about 2.5 mg, about 3.0 mg, about 3.5 mg, about 4.0 mg, about 4.5 mg, about 5.0 mg, about 5.5 mg, about 6.0 mg, about 6.5 mg, about 7.0 mg, about 7.5 mg, about 8.0 mg, about 8.5 mg, about 9.0 mg, about 9.5 mg, about 10.0 mg, about 10.5 mg, about 11 mg, about 11.5 mg, about 12 mg, about 12.5 mg, about 13 mg, about 13.5 mg, about 14 mg, about 14.5 mg, and about 15 mg, is administered to a patient three times daily. In some embodiments, about 2.0 mg to about 10 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient three times daily.

[0067]

[0071] In some embodiments, about 1.25 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 2.5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 7.5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 10 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 15 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 20 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 25 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 30 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 35 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 40 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 45 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 50 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof.

[0068]

[0072] In some embodiments, zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily to a patient in need thereof. In some embodiments, zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily to a patient in need thereof. In some embodiments, zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily to a patient in need thereof.

[0069]

[0073] In some embodiments, about 1.25 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 1.25 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 1.25 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily. In some embodiments, about 1.25 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered four times daily.

[0070]

[0074] In some embodiments, about 2.5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 2.5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 2.5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0071]

[0075] In some embodiments, about 5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0072]

[0076] In some embodiments, about 7.5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 7.5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 7.5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0073]

[0077] In some embodiments, about 10 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 10 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 10 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0074]

[0078] In some embodiments, about 15 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 15 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 15 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0075]

[0079] In some embodiments, about 20 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 20 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 20 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0076]

[0080] In some embodiments, about 25 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 25 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 25 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0077]

[0081] In some embodiments, about 30 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 30 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 30 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0078]

[0082] In some embodiments, about 35 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 35 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 35 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0079]

[0083] In some embodiments, about 40 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 40 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 40 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0080]

[0084] In some embodiments, about 45 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 45 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 45 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0081]

[0085] In some embodiments, about 50 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 50 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 50 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0082]

[0086] In some embodiments, the disclosed methods for treating symptoms associated with autism further comprise titrating the dose of zolmitriptan or a pharmaceutically acceptable salt thereof over a period of at least about one week until a steady state is achieved in the patient. In some embodiments, the titration occurs for about two weeks until a steady state is achieved in the patient. In some embodiments, the titration occurs for about seven days to about 30 days until a steady state is achieved in the patient. In some embodiments, the titration occurs for about 12 days to about 20 days until a steady state is achieved in the patient.

[0083]

[0087] In some embodiments, during titration, increasing doses of zolmitriptan or a pharmaceutically acceptable salt thereof are administered until a steady state is achieved in the patient. In some embodiments, during titration, increasing doses of zolmitriptan or a pharmaceutically acceptable salt thereof are administered until an effective dose of about 5 mg, about 7.5 mg, about 10.0 mg, about 12.5 mg, or about 15 mg is achieved in the patient.

[0084]

[0088] In some embodiments, titration begins at a dose of about 2.5 mg administered three times daily. In some embodiments, titration begins at a dose of about 5 mg administered three times daily.

[0085]

[0089] In some embodiments, the disclosed methods for treating symptoms associated with autism include starting with a dose of about 2.5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof three times daily and titrating to a dose of about 5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof three times daily. In some embodiments, the disclosed methods for treating symptoms associated with autism include starting with a dose of about 5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof three times daily and titrating to a dose of about 7.5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof three times daily. In some embodiments, the disclosed methods for treating symptoms associated with autism include starting with a dose of about 5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof three times daily and titrating to a dose of about 10 mg of zolmitriptan or a pharmaceutically acceptable salt thereof three times daily.

[0086]

[0090] In some embodiments, the methods of the present disclosure result in CSF levels of zolmitriptan that correlate with one or more statistically significant therapeutic effects. In some embodiments, therapeutically effective CSF levels of zolmitriptan resulting from the methods of the present disclosure are about 0.05 ng / mL, about 0.075 ng / mL, about 0.1 ng / mL, about 0.125 ng / mL, about 0.15 ng / mL, about 0.175 ng / mL, about 0.2 ng / mL, about 0.25 ng / mL, about 0.3 ng / mL, about 0.35 ng / mL, about 0.4 ng / mL, about 0.45 ng / mL, about 0.5 ng / mL, about 0.55 ng / mL, about 0.6 ng / mL, about 0.65 ng / mL, about 0.7 ng / mL, about 0.75 ng / mL, about 0.8 ng / mL, about 0.85 ng / mL, about 0.9 ...5 ng / mL, about 0.175 ng / mL, about 0.2 ng / mL, about 0. The range is from about 0.05ng / mL to about 2ng / mL (including all values ​​and ranges therebetween), including about 0.95ng / mL, about 1ng / mL, about 1.1ng / mL, about 1.15ng / mL, about 1.2ng / mL, about 1.25ng / mL, about 1.3ng / mL, about 1.35ng / mL, about 1.4ng / mL, about 1.45ng / mL, about 1.5ng / mL, about 1.55ng / mL, about 1.6ng / mL, about 1.65ng / mL, about 1.7ng / mL, about 1.75ng / mL, about 1.8ng / mL, about 1.85ng / mL, about 1.9ng / mL, about 1.95ng / mL, and about 2ng / mL. In some embodiments, the therapeutically effective CSF levels of zolmitriptan achieved by the methods of the present disclosure range from about 0.078 ng / mL to about 1.24 ng / mL. In some embodiments, the therapeutically effective CSF levels of zolmitriptan achieved by the methods of the present disclosure range from about 0.103 ng / mL to about 0.93 ng / mL.

[0087]

[0091] In some embodiments, the disclosed methods for treating symptoms associated with autism include administering naratriptan or a pharmaceutically acceptable salt thereof to a patient in need thereof. In some embodiments, the methods include administering about 0.5 mg, about 1.0 mg, about 1.5 mg, about 2.0 mg, about 2.5 mg, about 3.0 mg, about 3.5 mg, about 4.0 mg, about 4.5 mg, about 5.0 mg, about 5.5 mg, about 6.0 mg, about 6.5 mg, about 7.0 mg, about 7.5 mg, about 8.0 mg, about 8.5 mg, about 9.0 mg, about 9.5 mg, about 10.0 mg, about 10.5 mg, about 11.0 mg, about 11.5 mg, about 12.0 mg, about 12.5 mg, about 13.0 mg, about 13.5 mg, about 14.0 mg, about 14.5 mg, about 15.0 mg, about 15.5 mg, about 16.0 mg, about 16.5 mg, about 17.0 mg, about 17.5 mg, about 18.0 mg, about 18.5 mg, about 19.0 mg, about 19.5 mg, about 20.0 mg, about 20.5 mg, about 21.0 mg, about 21.5 mg, about 22.0 mg, about 22.5 mg, about 23.0 mg, about 23.5 mg, about 24.0 mg, about 24.5 mg, about 25.0 mg, about 25.5 mg, about 26.0 mg, about 26.5 mg, about 27.0 mg, about 27.5 mg, about 28.0 mg, about 28.5 mg, about 29.0 mg, about 29.5 mg, about 30.0 mg, about 30. In some embodiments, about 0.5 mg to about 20 mg (including all values ​​and ranges therebetween) of naratriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 0.5 mg to about 9 mg of naratriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 1 mg to about 5 mg of naratriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, the methods of the disclosure provide a method for administering a therapeutically effective amount of a medicament for the treatment of a patient with ... The method comprises administering 2.0 mg, about 12.5 mg, about 13.0 mg, about 13.5 mg, about 14.0 mg, about 14.5 mg, about 15.0 mg, about 15.5 mg, about 16.0 mg, about 16.5 mg, about 17.0 mg, about 17.5 mg, about 18.0 mg, about 18.5 mg, about 19.0 mg, about 19.5 mg, or about 20.0 mg of naratriptan or a pharmaceutically acceptable salt thereof to a patient in need thereof.In some embodiments, about 1 mg of naratriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof, hi some embodiments, about 2.5 mg of naratriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof.

[0088]

[0092] In some embodiments, naratriptan or a pharmaceutically acceptable salt thereof is administered once daily to a patient in need thereof. In some embodiments, naratriptan or a pharmaceutically acceptable salt thereof is administered twice daily to a patient in need thereof. In some embodiments, naratriptan or a pharmaceutically acceptable salt thereof is administered three times daily to a patient in need thereof.

[0089]

[0093] In some embodiments, about 1 mg of naratriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 1 mg of naratriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 1 mg of naratriptan or a pharmaceutically acceptable salt thereof is administered three times daily. In some embodiments, about 1 mg of naratriptan or a pharmaceutically acceptable salt thereof is administered four times daily.

[0090]

[0094] In some embodiments, about 2.5 mg of naratriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 2.5 mg of naratriptan or a pharmaceutically acceptable salt thereof is administered twice daily.

[0091]

[0095] In some embodiments, the methods of the present disclosure provide plasma levels of naratriptan (e.g., mean steady-state plasma levels) that correlate with one or more statistically significant therapeutic effects. In some embodiments, therapeutically effective plasma levels of naratriptan provided by the methods of the present disclosure are about 5 ng / mL, about 10 ng / ml, about 20 ng / ml, about 30 ng / ml, about 40 ng / ml, about 50 ng / ml, about 60 ng / ml, about 70 ng / ml, about 80 ng / ml, about 90 ng / ml, about 100 ng / ml, about 110 ng / ml, about 120 ng / ml, about 130 ng / ml, about 140 ng / ml, about 150 ng / ml, about In some embodiments, the therapeutically effective plasma levels of naratriptan produced by the methods of the present disclosure range from about 10 ng / mL to about 300 ng / mL, including all values ​​and ranges therebetween, such as 160 ng / mL, about 170 ng / mL, about 180 ng / mL, about 190 ng / mL, about 200 ng / mL, about 210 ng / mL, about 220 ng / mL, about 230 ng / mL, about 240 ng / mL, about 250 ng / mL, about 260 ng / mL, about 270 ng / mL, about 280 ng / mL, about 290 ng / mL, and about 300 ng / mL.

[0092]

[0096] In some embodiments, the methods of the disclosure provide a method for determining the level of a plasma concentration of about 5 ng / mL, 10 ng / ml, about 20 ng / ml, about 30 ng / ml, about 40 ng / ml, about 50 ng / ml, about 60 ng / ml, about 70 ng / ml, about 80 ng / ml, about 90 ng / ml, about 100 ng / ml, about 110 ng / ml, about 120 ng / ml, about 130 ng / ml, about 140 ng / ml, about 150 ng / ml, about 160 ng / ml, about 170 ng / ml, about 180 ng / ml, about 200 ng / ml, about 210 ng / ml, about 220 ng / ml, about 230 ng / ml, about 240 ng / ml, about 250 ng / ml, about 260 ng / ml, about 270 ng / ml, about 280 ng / ml, about 290 ng / ml, about 300 ng / ml, about 310 ng / ml, about 320 ng / ml, about 330 ng / ml, about 340 ng / ml, about 350 ng / ml, about 360 ng / ml, about 370 ng / ml, about 380 ng / ml, about 390 ng / ml, about 400 ng / ml, about 410 ng / ml, about 420 ng / ml, about 430 ng / ml, about 440 ng / ml, about 450 ng / ml, about 460 ng / ml, about 470 ng / ml, about 480 ng / ml, about 490 ng / ml, about 500 ng / ml, about In some embodiments, the disclosed methods result in a plasma Cmax of naratriptan of about 5 ng / mL to about 300 ng / mL, including 0 ng / mL, about 190 ng / mL, about 200 ng / mL, about 210 ng / mL, about 220 ng / mL, about 230 ng / mL, about 240 ng / mL, about 250 ng / mL, about 260 ng / mL, about 270 ng / mL, about 280 ng / mL, about 290 ng / mL, and about 300 ng / mL, inclusive of all values ​​and ranges therebetween. In some embodiments, the disclosed methods result in a plasma Cmax of naratriptan of about 12 ng / mL.

[0093]

[0097] In some embodiments, the disclosed methods for treating symptoms associated with autism include administering a therapeutically effective amount of rizatriptan or a pharmaceutically acceptable salt thereof to a patient in need thereof. In some embodiments, the methods include administering a therapeutically effective amount of about 1.0 mg, about 1.5 mg, about 2.0 mg, about 2.5 mg, about 3.0 mg, about 3.5 mg, about 4.0 mg, about 4.5 mg, about 5.0 mg, about 5.5 mg, about 6.0 mg, about 6.5 mg, about 7.0 mg, about 7.5 mg, about 8.0 mg, about 8.5 mg, about 9.0 mg, about 9.5 mg, about 10.0 mg, or about 10.5 mg of rizatriptan or a pharmaceutically acceptable salt thereof to a patient in need thereof. , about 11.0 mg, about 11.5 mg, about 12.0 mg, about 12.5 mg, about 13.0 mg, about 13.5 mg, about 14.0 mg, about 14.5 mg, about 15.0 mg, about 15.5 mg, about 16.0 mg, about 16.5 mg, about 17.0 mg, about 17.5 mg, about 18.0 mg, about 18.5 mg, about 19.0 mg, about 19.5 mg, about 20.0 mg, about 25 mg about 1 mg to about 200 mg (including all values ​​and ranges therebetween) of rizatriptan or a pharmaceutically acceptable salt thereof to a patient in need thereof. In some embodiments, about 11 mg to about 200 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 5 mg to about 30 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 5 mg to about 10 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof.In some embodiments, the methods of the disclosure provide a method for administering a therapeutically effective amount of a medicament for the treatment of a patient with ... .0mg, approximately 10.5mg, approximately 11.0mg, approximately 11.5mg, approximately 12.0mg, approximately 12.5mg, approximately 13.0mg, approximately 13.5mg, approximately 14.0mg, approximately 14.5mg, approximately 15.0mg, approximately 15.5mg, approximately 16.0mg, approximately 16.5mg, approximately 17.0mg, approximately 17.5mg, approximately 18.0mg, approximately 18.5mg, approximately 19.0mg, approximately The present invention relates to a method for administering 19.5 mg, about 20.0 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, about 100 mg, about 105 mg, about 110 mg, about 115 mg, about 120 mg, about 125 mg, about 130 mg, about 135 mg, about 140 mg, about 145 mg, about 150 mg, about 155 mg, about 160 mg, about 165 mg, about 170 mg, about 175 mg, about 180 mg, about 185 mg, about 190 mg, about 195 mg, or about 200 mg of rizatriptan or a pharmaceutically acceptable salt thereof to a patient in need thereof. In some embodiments, about 5 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof, hi some embodiments, about 10.0 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof.

[0094]

[0098] In some embodiments, rizatriptan or a pharmaceutically acceptable salt thereof is administered once daily to a patient in need thereof. In some embodiments, rizatriptan or a pharmaceutically acceptable salt thereof is administered twice daily to a patient in need thereof. In some embodiments, rizatriptan or a pharmaceutically acceptable salt thereof is administered three times daily to a patient in need thereof.

[0095]

[0099] In some embodiments, about 5 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 5 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 5 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered three times daily. In some embodiments, about 5 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered four times daily.

[0096]

[0100] In some embodiments, about 10 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 10 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 10 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered three times daily. In some embodiments, about 10 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered four times daily.

[0097]

[0101] In some embodiments, the methods of the present disclosure provide plasma levels of rizatriptan (e.g., mean steady-state plasma levels) that correlate with one or more statistically significant therapeutic effects. In some embodiments, therapeutically effective plasma levels of rizatriptan provided by the methods of the present disclosure are about 5 ng / mL, about 10 ng / ml, about 20 ng / ml, about 30 ng / ml, about 40 ng / ml, about 50 ng / ml, about 60 ng / ml, about 70 ng / ml, about 80 ng / ml, about 90 ng / ml, about 100 ng / ml, about 110 ng / ml, about 120 ng / ml, about 130 ng / ml, about 140 ng / ml, about 150 ng / ml, about The range is from about 5 ng / mL to about 300 ng / mL (including all values ​​and ranges therebetween), including 160 ng / mL, about 170 ng / mL, about 180 ng / mL, about 190 ng / mL, about 200 ng / mL, about 210 ng / mL, about 220 ng / mL, about 230 ng / mL, about 240 ng / mL, about 250 ng / mL, about 260 ng / mL, about 270 ng / mL, about 280 ng / mL, about 290 ng / mL, and about 300 ng / mL.

[0098]

[0102] In some embodiments, the methods of the disclosure provide a method for determining the level of a plasma concentration of about 5 ng / mL, 10 ng / ml, about 20 ng / ml, about 30 ng / ml, about 40 ng / ml, about 50 ng / ml, about 60 ng / ml, about 70 ng / ml, about 80 ng / ml, about 90 ng / ml, about 100 ng / ml, about 110 ng / ml, about 120 ng / ml, about 130 ng / ml, about 140 ng / ml, about 150 ng / ml, about 160 ng / ml, about 170 ng / ml, about 180 ng / ml, about 200 ng / ml, about 210 ng / ml, about 220 ng / ml, about 230 ng / ml, about 240 ng / ml, about 250 ng / ml, about 260 ng / ml, about 270 ng / ml, about 280 ng / ml, about 290 ng / ml, about 300 ng / ml, about 310 ng / ml, about 320 ng / ml, about 330 ng / ml, about 340 ng / ml, about 350 ng / ml, about 360 ng / ml, about 370 ng / ml, about 380 ng / ml, about 390 ng / ml, about 400 ng / ml, about 410 ng / ml, about 420 ng / ml, about 430 ng / ml, about 440 ng / ml, about 450 ng / ml, about 460 ng / ml, about 470 ng / ml, about 480 ng / ml, about 490 ng / ml, about 500 ng / ml, about The disclosed methods result in a plasma Cmax of rizatriptan of about 5 ng / mL to about 300 ng / mL (including all values ​​and ranges therebetween), including 0 ng / mL, about 190 ng / mL, about 200 ng / mL, about 210 ng / mL, about 220 ng / mL, about 230 ng / mL, about 240 ng / mL, about 250 ng / mL, about 260 ng / mL, about 270 ng / mL, about 280 ng / mL, about 290 ng / mL, and about 300 ng / mL. In some embodiments, the disclosed methods result in a Cmax of rizatriptan of about 5 ng / mL to about 50 ng / mL. In some embodiments, the disclosed methods result in a Cmax of rizatriptan of about 6 ng / mL, about 13 ng / mL, about 29 ng / mL, or about 44.8 ng / mL.

[0099]

[0103] In some embodiments, the disclosed methods for treating symptoms associated with autism include administering a therapeutically effective amount of almotriptan or a pharmaceutically acceptable salt thereof to a patient in need thereof. In some embodiments, the methods ... 12.5 mg, about 13 mg, about 13.5 mg, about 14 mg, about 14.5 mg, and about 15 mg, about 15.5 mg, about 15.75 mg, about 16.0 mg, about 16.25 mg, about 16.5 mg, about 16.75 mg, about 17.0 mg, about 17.5 mg, about 18.0 mg, about 18.5 mg, about 19.0 mg, about 19.5 mg, about 20.0 mg, about 20.5 mg This involves administering to a patient in need thereof about 5.0 mg to about 30.0 mg (including all values ​​and ranges therebetween) of almotriptan or a pharmaceutically acceptable salt thereof, including about 21 mg, about 21.5 mg, about 22 mg, about 22.5 mg, about 23 mg, about 23.5 mg, about 24 mg, about 24.5 mg, about 25 mg, about 25.5 mg, about 26 mg, about 26.5 mg, about 27 mg, about 27.5 mg, about 28 mg, about 28.5 mg, about 29 mg, about 29.5 mg, and about 30 mg. In some embodiments, about 6 mg to about 25 mg of almotriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof.In some embodiments, the methods of the disclosure provide a method for administering a dose of about 5.0 mg, about 5.25 mg, about 5.5 mg, about 5.75 mg, about 6.0 mg, about 6.25 mg, about 6.5 mg, about 6.75 mg, about 7.0 mg, about 7.5 mg, about 8.0 mg, about 8.5 mg, about 9.0 mg, about 9.5 mg, about 10.0 mg, about 10.5 mg, about 11 mg, about 11.5 mg, about 12 mg , about 12.5mg, about 13mg, about 13.5mg, about 14mg, about 14.5mg, about 15mg, about 15.5mg, about 15.75mg, about 16.0mg, about 16.25mg, about 16.5mg, about 16.75mg, about 17.0mg, about 17.5mg, about 18.0mg, about 18.5mg, about 19.0mg, about 19.5mg, about 20.0mg, about 20.5mg Some embodiments include administering about 21 mg, about 21.5 mg, about 22 mg, about 22.5 mg, about 23 mg, about 23.5 mg, about 24 mg, about 24.5 mg, about 25 mg, about 25.5 mg, about 26 mg, about 26.5 mg, about 27 mg, about 27.5 mg, about 28 mg, about 28.5 mg, about 29 mg, about 29.5 mg, and about 30 mg of almotriptan or a pharmaceutically acceptable salt thereof to a patient in need thereof. In some embodiments, about 6.25 mg of almotriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 12.5 mg of almotriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof.

[0100]

[0104] In some embodiments, almotriptan or a pharmaceutically acceptable salt thereof is administered once daily to a patient in need thereof. In some embodiments, almotriptan or a pharmaceutically acceptable salt thereof is administered twice daily to a patient in need thereof. In some embodiments, almotriptan or a pharmaceutically acceptable salt thereof is administered three times daily to a patient in need thereof.

[0101]

[0105] In some embodiments, about 6.25 mg of almotriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 6.25 mg of almotriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 6.25 mg of almotriptan or a pharmaceutically acceptable salt thereof is administered three times daily. In some embodiments, about 6.25 mg of almotriptan or a pharmaceutically acceptable salt thereof is administered four times daily.

[0102]

[0106] In some embodiments, about 12.5 mg of almotriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 12.5 mg of almotriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 12.5 mg of almotriptan or a pharmaceutically acceptable salt thereof is administered three times daily. In some embodiments, about 12.5 mg of almotriptan or a pharmaceutically acceptable salt thereof is administered four times daily.

[0103]

[0107] In some embodiments, the methods of the present disclosure provide plasma levels of almotriptan (e.g., mean steady-state plasma levels) that correlate with one or more statistically significant therapeutic effects. In some embodiments, therapeutically effective plasma levels of almotriptan provided by the methods of the present disclosure are about 20 ng / ml, about 30 ng / ml, about 40 ng / ml, about 50 ng / ml, about 60 ng / ml, about 70 ng / ml, about 80 ng / ml, about 90 ng / ml, about 100 ng / ml, about 110 ng / ml, about 120 ng / ml, about 130 ng / ml, about 140 ng / ml, about 150 ng / ml, about 160 ng / ml, about 170 ng / ml, about 180 ng / ml, about 190 ng / ml, about 210 ng / ml, about 220 ng / ml, about 230 ng / ml, about 240 ng / ml, about 250 ng / ml, about 260 ng / ml, about 270 ng / ml, about 280 ng / ml, about 290 ng / ml, about 300 ng / ml, about 310 ng / ml, about 320 ng / ml, about 330 ng / ml, about 340 ng / ml, about 350 ng / ml, about 360 ng / ml, about 370 ng / ml, about 380 ng / ml, about 390 ng / ml, about 400 ng / ml, about 410 ng / ml, about 420 ng / ml, about 430 ng / ml, about 440 ng / ml, about 450 ng / ml, about 460 ng / ml, about 470 ng / ml, about 4 ml, about 150ng / ml, about 160ng / ml, about 170ng / ml, about 180ng / ml, about 190ng / ml, about 200ng / ml, about 210ng / ml, about 220ng / ml, about 2 30ng / ml, about 240ng / ml, about 250ng / ml, about 260ng / ml, about 270ng / ml, about 280ng / ml, about 290ng / ml, about 300ng / ml, about 310ng / ml ml, about 320ng / ml, about 330ng / ml, about 340ng / ml, about 350ng / ml, about 360ng / ml, about 370ng / ml, about 380ng / ml, about 390ng / ml, about 4 00ng / ml, approx. 410ng / ml, approx. 420ng / ml, approx. 430ng / ml, approx. 440ng / ml, approx. 450ng / ml, approx. 460ng / ml, approx. 470ng / ml, approx. 480ng / The range is from about 20 to about 600 ng / ml (including all values ​​and ranges therebetween), including about 490 ng / ml, about 500 ng / ml, about 510 ng / ml, about 520 ng / ml, about 530 ng / ml, about 540 ng / ml, about 550 ng / ml, about 560 ng / ml, about 570 ng / ml, about 580 ng / ml, about 590 ng / ml, and about 600 ng / ml.

[0104]

[0108] In some embodiments, the methods of the disclosure provide a method for detecting a plasma concentration of about 20 ng / ml, about 30 ng / ml, about 40 ng / ml, about 50 ng / ml, about 60 ng / ml, about 70 ng / ml, about 80 ng / ml, about 90 ng / ml, about 100 ng / ml, about 110 ng / ml, about 120 ng / ml, about 130 ng / ml, about 140 ng / ml, about 150 ng / ml, about 160 ng / ml, about 170 ng / ml, about 180 ng / ml, about 190 ng / ml, about 20 ng / ml, about 210 ng / ml, about 220 ng / ml, about 230 ng / ml, about 240 ng / ml, about 250 ng / ml, about 260 ng / ml, about 270 ng / ml, about 280 ng / ml, about 290 ng / ml, about 300 ng / ml, about 310 ng / ml, about 320 ng / ml, about 330 ng / ml, about 340 ng / ml, about 350 ng / ml, about 360 ng / ml, about 370 ng / ml, about 380 ng / ml, about 390 ng / ml, about 400 ng / ml, about 410 ng / ml, about 420 ng / ml, about 430 ng / ml, about 440 ng / ml, about 450 ng / ml, about 460 ng / ml, about 470 ng / ml, about 480 ng / ml, about 490 ng / ml, about 500 ng / ml, about 510 ng / ml, about g / ml, approximately 180ng / ml, approximately 190ng / ml, approximately 200ng / ml, approximately 210ng / ml, approximately 220ng / ml, approximately 230ng / ml, approximately 240ng / ml, approximately 250ng / m l, about 260ng / ml, about 270ng / ml, about 280ng / ml, about 290ng / ml, about 300ng / ml, about 310ng / ml, about 320ng / ml, about 330ng / ml, about 3 40ng / ml, approximately 350ng / ml, approximately 360ng / ml, approximately 370ng / ml, approximately 380ng / ml, approximately 390ng / ml, approximately 400ng / ml, approximately 410ng / ml, approximately 420n g / ml, approx. 430ng / ml, approx. 440ng / ml, approx. 450ng / ml, approx. 460ng / ml, approx. 470ng / ml, approx. 480ng / ml, approx. 490ng / ml, approx. 500ng / ml In some embodiments, the disclosed methods result in a plasma Cmax of almotriptan of about 20 ng / mL to about 600 ng / mL, including about 510 ng / mL, about 520 ng / mL, about 530 ng / mL, about 540 ng / mL, about 550 ng / mL, about 560 ng / mL, about 570 ng / mL, about 580 ng / mL, about 590 ng / mL, and about 600 ng / mL. In some embodiments, the disclosed methods result in a plasma Cmax of almotriptan of about 52 ng / mL to about 55 ng / mL.

[0105]

[0109] In some embodiments, the disclosed methods for treating symptoms associated with autism include administering a therapeutically effective amount of frovatriptan or a pharmaceutically acceptable salt thereof to a patient in need thereof. In some embodiments, the methods include administering a therapeutically effective amount of about 1.0 mg, about 1.5 mg, about 2.0 mg, about 2.5 mg, about 3.0 mg, about 3.5 mg, about 4.0 mg, about 4.5 mg, about 5.0 mg, about 5.5 mg, about 6.0 mg, about 6.5 mg, about 7.0 mg, about 7.5 mg, about 8.0 mg, about 8.5 mg, about 9.0 mg, about 9.5 mg, about 10.0 mg, or about 10.5 mg. , about 11.0 mg, about 11.5 mg, about 12.0 mg, about 12.5 mg, about 13.0 mg, about 13.5 mg, about 14.0 mg, about 14.5 mg, about 15.0 mg, about 15.5 mg, about 16.0 mg, about 16.5 mg, about 17.0 mg, about 17.5 mg, about 18.0 mg, about 18.5 mg, about 19.0 mg, about 19.5 mg, about 20.0 mg, about 25 mg, The method comprises administering about 1.0 mg to about 200 mg (including all values ​​and ranges therebetween) of frovatriptan or a pharmaceutically acceptable salt thereof to a patient in need thereof, including about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, about 100 mg, about 105 mg, about 110 mg, about 115 mg, about 120 mg, about 125 mg, about 130 mg, about 135 mg, about 140 mg, about 145 mg, about 150 mg, about 155 mg, about 160 mg, about 165 mg, about 170 mg, about 175 mg, about 180 mg, about 185 mg, about 190 mg, about 195 mg, and about 200 mg. In some embodiments, about 11 mg to about 193 mg of frovatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof, hi some embodiments, about 2 mg to about 7.5 mg of frovatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof.

[0106]

[0110] In some embodiments, the methods of the disclosure provide a method for administering a therapeutically effective amount of a medicament for the treatment of a patient with ... .0mg, approximately 10.5mg, approximately 11.0mg, approximately 11.5mg, approximately 12.0mg, approximately 12.5mg, approximately 13.0mg, approximately 13.5mg, approximately 14.0mg, approximately 14.5mg, approximately 15.0mg, approximately 15.5mg, approximately 16.0mg, approximately 16.5mg, approximately 17.0mg, approximately 17.5mg, approximately 18.0mg, approximately 18.5mg, approximately 19.0mg, approximately The present invention relates to a method for administering 19.5 mg, about 20.0 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, about 100 mg, about 105 mg, about 110 mg, about 115 mg, about 120 mg, about 125 mg, about 130 mg, about 135 mg, about 140 mg, about 145 mg, about 150 mg, about 155 mg, about 160 mg, about 165 mg, about 170 mg, about 175 mg, about 180 mg, about 185 mg, about 190 mg, about 195 mg, or about 200 mg of frovatriptan or a pharmaceutically acceptable salt thereof to a patient in need thereof. In some embodiments, about 2.5 mg of frovatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof.

[0107]

[0111] In some embodiments, frovatriptan or a pharmaceutically acceptable salt thereof is administered once daily to a patient in need thereof. In some embodiments, frovatriptan or a pharmaceutically acceptable salt thereof is administered twice daily to a patient in need thereof. In some embodiments, frovatriptan or a pharmaceutically acceptable salt thereof is administered three times daily to a patient in need thereof.

[0108]

[0112] In some embodiments, about 2.5 mg of frovatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 2.5 mg of frovatriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 2.5 mg of frovatriptan or a pharmaceutically acceptable salt thereof is administered three times daily. In some embodiments, about 2.5 mg of frovatriptan or a pharmaceutically acceptable salt thereof is administered four times daily.

[0109]

[0113] In some embodiments, the methods of the present disclosure result in plasma levels of frovatriptan (e.g., mean steady-state plasma levels) that correlate with one or more statistically significant therapeutic effects. In some embodiments, the therapeutically effective plasma levels of frovatriptan resulting from the methods of the present disclosure range from about 2 ng / mL to about 60 ng / mL (including all values ​​and ranges therebetween), including about 2 ng / mL, about 2.5 ng / mL, about 3 ng / mL, about 3.5 ng / mL, about 4 ng / mL, about 4.5 ng / mL, about 5 ng / mL, about 6 ng / mL, about 7 ng / mL, about 8 ng / mL, about 9 ng / mL, about 10 ng / mL, about 15 ng / mL, 20 ng / mL, about 25 ng / mL, about 30 ng / mL, about 35 ng / mL, about 40 ng / mL, about 45 ng / mL, about 50 ng / mL, about 55 ng / mL, and about 60 ng / mL.

[0110]

[0114] In some embodiments, the disclosed methods result in a plasma Cmax of frovatriptan of about 2 ng / mL to about 60 ng / mL (including all values ​​and ranges therebetween), including about 2 ng / mL, about 2.5 ng / mL, about 3 ng / mL, about 3.5 ng / mL, about 4 ng / mL, about 4.5 ng / mL, about 5 ng / mL, about 6 ng / mL, about 7 ng / mL, about 8 ng / mL, about 9 ng / mL, about 10 ng / mL, about 15 ng / mL, about 20 ng / mL, about 25 ng / mL, about 30 ng / mL, about 35 ng / mL, about 40 ng / mL, about 45 ng / mL, about 50 ng / mL, about 55 ng / mL, and about 60 ng / mL. In some embodiments, the disclosed methods result in a plasma Cmax of frovatriptan of about 2.5 ng / mL.

[0111]

[0115] In some embodiments, the disclosed methods for treating symptoms associated with autism include administering a therapeutically effective amount of eletriptan or a pharmaceutically acceptable salt thereof to a patient in need thereof. In some embodiments, the methods include administering a therapeutically effective amount of about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, about 100 mg, about 105 mg, about 110 mg, about 115 mg, about 120 mg, about 125 mg, about 130 mg, about 135 mg, about 140 mg, about 145 mg, about 150 mg, about This includes administering about 10 mg to about 250 mg of eletriptan (including all values ​​and ranges therebetween), including about 155 mg, about 160 mg, about 165 mg, about 170 mg, about 175 mg, about 180 mg, about 185 mg, about 190 mg, about 195 mg, about 200 mg, about 205 mg, about 210 mg, about 215 mg, about 220 mg, about 225 mg, about 230 mg, about 235 mg, about 240 mg, and about 250 mg, to a patient in need thereof. In some embodiments, about 13 mg to about 235 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 20 mg to about 40 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 20 mg to about 80 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof.In some embodiments, the methods of the disclosure provide a method for administering a therapeutically effective amount of a medicament for a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a medicament for a patient in need thereof, the method ... The present invention relates to a method for administering eletriptan or a pharmaceutically acceptable salt thereof to a patient in need thereof, the method comprising administering about 145 mg, about 150 mg, about 155 mg, about 160 mg, about 165 mg, about 170 mg, about 175 mg, about 180 mg, about 185 mg, about 190 mg, about 195 mg, about 200 mg, about 205 mg, about 210 mg, about 215 mg, about 220 mg, about 225 mg, about 230 mg, about 235 mg, about 240 mg, or about 250 mg of eletriptan or a pharmaceutically acceptable salt thereof to a patient in need thereof. In some embodiments, about 20 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof. In some embodiments, about 40 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need thereof.

[0112]

[0116] In some embodiments, eletriptan or a pharmaceutically acceptable salt thereof is administered once daily to a patient in need thereof. In some embodiments, eletriptan or a pharmaceutically acceptable salt thereof is administered twice daily to a patient in need thereof. In some embodiments, eletriptan or a pharmaceutically acceptable salt thereof is administered three times daily to a patient in need thereof.

[0113]

[0117] In some embodiments, about 20 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 20 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 20 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered three times daily. In some embodiments, about 20 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered four times daily.

[0114]

[0118] In some embodiments, about 40 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 40 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 40 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered three times daily. In some embodiments, about 40 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered four times daily.

[0115]

[0119] In some embodiments, the methods of the present disclosure provide plasma levels of eletriptan (eg, mean steady-state plasma levels) that correlate with one or more statistically significant therapeutic effects. In some embodiments, the therapeutically effective plasma levels of eletriptan provided by the methods of the present disclosure are about 40 ng / ml, about 60 ng / mL, about 80 ng / ml, about 100 ng / ml, about 120 ng / ml, about 140 ng / ml, about 160 ng / ml, about 180 ng / ml, about 200 ng / ml, about 220 ng / ml, about 240 ng / ml, about 260 ng / ml, about 280 ng / ml, about 300 ng / ml, about 320 ng / ml, about 340 ng / ml, about 360 ng / ml, about 380 ng / ml, about 400 ng / ml, about 420 ng / ml, about 440 ng / ml, about 460 ng / ml, about 480 ng / ml, about 500 ng / ml, about 520 ng / ml, about 540 ng / ml, about 560 ng / ml, about The range is from about 40ng / mL to about 1200ng / mL (including all values ​​and ranges therebetween), including 580ng / mL, about 600ng / mL, about 620ng / mL, about 640ng / mL, about 660ng / mL, about 680ng / mL, about 700ng / mL, about 720ng / mL, about 740ng / mL, about 760ng / mL, about 780ng / mL, about 800ng / mL, about 820ng / mL, about 840ng / mL, about 860ng / mL, about 880ng / mL, about 900ng / mL, about 920ng / mL, about 940ng / mL, about 960ng / mL, about 980ng / mL, about 1000ng / mL, about 1050ng / mL, about 1100ng / mL, about 1150ng / mL, and about 1200ng / mL.

[0116]

[0120] In some embodiments, the methods of the disclosure provide a method for determining the level of a plasma concentration of about 40 ng / ml, about 60 ng / ml, about 80 ng / ml, about 100 ng / ml, about 120 ng / ml, about 140 ng / ml, about 160 ng / ml, about 180 ng / ml, about 200 ng / ml, about 220 ng / ml, about 240 ng / ml, about 260 ng / ml, about 280 ng / ml, about 300 ng / ml, about 320 ng / ml, about 340 ng / ml, about 360 ng / ml, about 380 ng / ml, about 400 ng / ml, about 420 ng / ml, about 440 ng / ml, about 460 ng / ml, about 480 ng / ml, about 500 ng / ml, about 520 ng / ml, about 540 ng / ml, about 560 ng / ml, about 580 ng / ml, about 600 ng / ml, about 6 provides a plasma Cmax of eletriptan of about 40 ng / mL to about 1200 ng / mL (including all values ​​and ranges therebetween), including 20 ng / mL, about 640 ng / mL, about 660 ng / mL, about 680 ng / mL, about 700 ng / mL, about 720 ng / mL, about 740 ng / mL, about 760 ng / mL, about 780 ng / mL, about 800 ng / mL, about 820 ng / mL, about 840 ng / mL, about 860 ng / mL, about 880 ng / mL, about 900 ng / mL, about 920 ng / mL, about 940 ng / mL, about 960 ng / mL, about 980 ng / mL, about 1000 ng / mL, about 1050 ng / mL, about 1100 ng / mL, about 1150 ng / mL, and about 1200 ng / mL. In some embodiments, the disclosed methods result in a plasma Cmax of eletriptan of about 45 ng / mL to about 210 ng / mL, hi some embodiments, the disclosed methods result in a plasma Cmax of eletriptan of about 46.5 ng / mL, about 94.5 ng / mL, or about 200 ng / mL.

[0117]

[0121] In some embodiments, the triptan is administered one or more times per day. In some embodiments, the triptan is administered once per day. In some embodiments, the triptan is administered twice per day. In some embodiments, the triptan is administered three times per day. In some embodiments, the triptan is administered more than three times per day.

[0118]

[0122] In some embodiments, the present disclosure provides a method for treating irritability associated with autism, comprising administering a therapeutically effective amount of a triptan. In some embodiments, the present disclosure provides a method for treating autism-associated aggression, comprising administering an effective amount of a triptan or a pharmaceutically acceptable salt thereof. In some embodiments, the present disclosure provides a method for treating apathy associated with autism, comprising administering an effective amount of a triptan or a pharmaceutically acceptable salt thereof. In some embodiments, the present disclosure provides a method for treating social symptoms associated with autism, comprising administering an amount of a triptan effective to improve socialization. In some embodiments, the present disclosure provides a method for reducing social deficits associated with autism, comprising administering an effective amount of a triptan or a pharmaceutically acceptable salt thereof.

[0119]

[0123] In some embodiments, after treatment, the patient experiences a substantial reduction in symptoms associated with ASD (e.g., social symptoms, aggression, or irritability) compared to before said treatment. Non-limiting examples of ASD symptoms include irritability, difficulty communicating, difficulty with social interaction, obsessive-compulsive interests, repetitive behaviors, inappropriate social interactions, poor eye contact, compulsive behaviors, impulsivity, repetitive movements, self-injury, persistent repetitive speech or behaviors, learning disabilities, delayed speech, a strong interest in a limited number of things, problems paying attention, lack of awareness of others' emotions, depression, anxiety, changes in voice, sensitivity to sounds, and tics. In some embodiments, the patient in need thereof experiences a substantial reduction in irritability associated with ASD compared to before said treatment. In some embodiments, the patient in need thereof experiences a substantial improvement in socialization compared to before said treatment. In some embodiments, the patient in need thereof experiences a substantial reduction in aggression associated with ASD compared to before said treatment.

[0120]

[0124] The Vineland Adaptive Behavior Scales (VABS), Third Edition, is a standardized measure of adaptive behavior used to assess an individual's personal and social skills from birth to adulthood. Individuals can be assessed on the VABS by either a teacher or caregiver. According to the VABS, individuals are assigned a VABS Adaptive Behavior Composite Score, which measures the individual's functioning relative to others of their age. Individuals are also assigned domain scores in communication, daily living skills, socialization, and motor skills, which assess the strengths and weaknesses of the individual's adaptive behavior. Individuals are assigned a score from 20 to 140 for each domain score and the VABS Adaptive Behavior Composite Score. A score of 20 to 70 indicates poor adjustment. A score of 71 to 85 indicates moderately poor adjustment. A score of 86 to 114 indicates moderately adequate adjustment. A score of 115 to 129 indicates moderately adequate adjustment. A score of 130-140 indicates a high level of adaptation.

[0121]

[0125] In some embodiments, after said treatment, the patient experiences a reduction in symptoms associated with ASD characterized by an increase of at least one point on the VABS Adaptive Behavior Composite score compared to before said treatment. In some embodiments, the increase in the VABS Adaptive Behavior score is about 1 point, about 2 points, about 3 points, about 4 points, about 5 points, about 6 points, about 7 points, about 8 points, about 9 points, about 10 points, about 11 points, about 12 points, about 13 points, about 14 points, about 15 points, about 16 points, about 17 points, about 18 points, about 19 points, about 20 points, about 21 points, about 22 points, about 23 points, about 24 points, about 25 points, about 26 points, about 27 points, about 28 points, about 29 points, about 30 points, about 31 points, about 32 points, about 33 points, or about 34 points compared to before said treatment. about 34 points, about 35 points, about 36 points, about 37 points, about 38 points, about 39 points, about 40 points, about 41 points, about 42 points, about 43 points, about 44 points, about 45 points, about 46 points, about 47 points, about 48 points, about 49 points, about 50 points, about 51 points, about 52 points, about 53 points, about 54 points, about 55 points, about 56 points, about 57 points, about 58 points, about 59 points, about 60 points, about 61 points, about 62 points, about 63 points, about 64 points, about 65 points, about 66 points, about 67 points, about 68 points, about 69 points, or about 70 points.

[0122]

[0126] In some embodiments, the increase in the VABS Adaptive Behavior Composite score compared to before said treatment is at least about 1%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, or at least about 60%.

[0123]

[0127] In some embodiments, after said treatment, the patient exhibits increased sociability, characterized by an increase in the VABS Adaptive Behavior and Socialization domain score compared to before said treatment. In some embodiments, the increase in the VABS Adaptive Behavior and Socialization domain score is about 1 point, about 2 points, about 3 points, about 4 points, about 5 points, about 6 points, about 7 points, about 8 points, about 9 points, about 10 points, about 11 points, about 12 points, about 13 points, about 14 points, about 15 points, about 16 points, about 17 points, about 18 points, about 19 points, about 20 points, about 21 points, about 22 points, about 23 points, about 24 points, about 25 points, about 26 points, about 27 points, about 28 points, about 29 points, about 30 points, about 31 points, about 32 points, or about 33 points compared to before said treatment. , about 33 points, about 34 points, about 35 points, about 36 points, about 37 points, about 38 points, about 39 points, about 40 points, about 41 points, about 42 points, about 43 points, about 44 points, about 45 points, about 46 points, about 47 points, about 48 points, about 49 points, about 50 points, about 51 points, about 52 points, about 53 points, about 54 points, about 55 points, about 56 points, about 57 points, about 58 points, about 59 points, about 60 points, about 61 points, about 62 points, about 63 points, about 64 points, about 65 points, about 66 points, about 67 points, about 68 points, about 69 points, or about 70 points.

[0124]

[0128] In some embodiments, the increase in the VABS Adaptive Behavior Socialization domain score compared to before said treatment is at least about 1%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, or at least about 60%. In some embodiments, the patient experiences at least a 10% improvement in the VABS Socialization domain score after treatment. In some embodiments, the patient experiences at least a 35% improvement in the VABS Socialization domain score after treatment.

[0125]

[0129] In some embodiments, after the treatment, the patient experiences improved communication characterized by an increase in the VABS Adaptive Behavior Communication domain score compared to before treatment. In some embodiments, the increase in the VABS Adaptive Behavior Communication domain is about 1 point, about 2 points, about 3 points, about 4 points, about 5 points, about 6 points, about 7 points, about 8 points, about 9 points, about 10 points, about 11 points, about 12 points, about 13 points, about 14 points, about 15 points, about 16 points, about 17 points, about 18 points, about 19 points, about 20 points, about 21 points, about 22 points, about 23 points, about 24 points, about 25 points, about 26 points, about 27 points, about 28 points, about 29 points, about 30 points, about 31 points, about 32 points, or about 33 points compared to before treatment. , about 33 points, about 34 points, about 35 points, about 36 points, about 37 points, about 38 points, about 39 points, about 40 points, about 41 points, about 42 points, about 43 points, about 44 points, about 45 points, about 46 points, about 47 points, about 48 points, about 49 points, about 50 points, about 51 points, about 52 points, about 53 points, about 54 points, about 55 points, about 56 points, about 57 points, about 58 points, about 59 points, about 60 points, about 61 points, about 62 points, about 63 points, about 64 points, about 65 points, about 66 points, about 67 points, about 68 points, about 69 points, or about 70 points.

[0126]

[0130] In some embodiments, the increase in the VABS Adaptive Behavioral Communication domain score compared to before said treatment is at least about 1%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, or at least about 60%.

[0127]

[0131] The Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) is an instrument capable of accurately assessing and diagnosing ASD across all age groups, developmental levels, and language skills. The ADOS-2 is a clinician-administered observational assessment that includes two behavioral domains: social-emotional (SA) and restricted repetitive behaviors (RRB). Individuals complete one of five ADOS-2 modules, selected based on the individual's expressive language level and chronological age. The Toddler Module is for children aged 12 to 30 months who do not use consistent phrased speech. Module 1 is for children aged 31 months and older who do not use consistent phrased speech. Module 2 is for children of any age who use phrased speech but are not fluent. Module 3 is for children and young adolescents who are fluent speakers. Module 4 is for older adolescents and adults who are fluent speakers. Individuals are assigned an ADOS-2 composite total score ranging from 1 to 10. Individuals with ASD are characterized by an ADOS-2 composite total score of 6 to 10.

[0128]

[0132] In some embodiments, the patient experiences a reduction in symptoms associated with ASD associated with at least a 1-point decrease in the ADOS-2 composite total score compared to before said treatment, hi some embodiments, the patient experiences an improvement in symptoms of ASD characterized by a decrease of at least 1 point, at least 2 points, at least 3 points, at least 4 points, or at least 5 points on the ADOS-2 composite total score compared to before said treatment.

[0129]

[0133] In some embodiments, the patient experiences an improvement in symptoms of ASD characterized by an improvement of at least about 5%, or at least about 10%, or at least about 15%, or at least about 20%, or at least about 25%, or at least about 30%, or at least about 35%, or at least about 40%, or at least about 45%, or at least about 50%, or at least about 55%, or at least about 60%, or at least about 65%, or at least about 70%, or at least about 75%, or at least about 80%, or at least about 85%, or at least about 90% in ADOS-2 composite score compared to before said treatment.

[0130]

[0134] In some embodiments, the patient experiences a reduction in symptoms associated with ASD characterized by a decrease of at least one point on an ADOS-2 Module 4 Social-Emotional score compared to before said treatment. In some embodiments, a decrease in ADOS-2 Module 4 Social-Emotional score correlates with improved sociality. In some embodiments, improved sociality is characterized by a decrease of at least one point, or at least two points, or at least three points, or at least four points, or at least five points, or at least six points on the Social-Emotional score on the ADOS-2 Module 4 compared to before said treatment.

[0131]

[0135] In some embodiments, the improvement in social skills is characterized by at least a 10%, or at least a 15%, or at least a 20%, or at least a 25%, or at least a 30%, or at least a 35%, or at least a 40%, or at least a 45%, or at least a 50%, or at least a 55% decrease in the Social Emotional scale on the ADOS-2 Module 4 compared to before said treatment. In some embodiments, the patient exhibits improvement in social skills characterized by at least a 10% decrease in the Social Interactions score on the Autism Diagnostic Observation Schedule Module 4 compared to before said treatment.

[0132]

[0136] The Clinical Global Impression-Severity (CGI-S) scale is used by clinicians to rate the severity of symptoms in individuals with ASD. Individuals are assigned a score of 1 to 7, with a score of 1 corresponding to a normal individual and a score of 7 corresponding to an individual with ASD.

[0133]

[0137] In some embodiments, after said treatment, the patient experiences a reduction in symptoms associated with ASD characterized by a decrease in CGI-S score of at least 1 point compared to before said treatment, hi some embodiments, the patient experiences a decrease of at least 1 point, or at least 2 points, or at least 3 points, or at least 4 points, or at least 5 points on the CGI-S scale compared to before said treatment.

[0134]

[0138] In some embodiments, the patient experiences at least a 5%, or at least a 10%, or at least a 15%, or at least a 20%, or at least a 25%, or at least a 30%, or at least a 35%, or at least a 40%, or at least a 45%, or at least a 50%, or at least a 55%, or at least a 60%, or at least a 65%, or at least a 70%, or at least a 75%, or at least a 80%, or at least a 85%, or at least a 90% reduction in the CGI-S scale compared to before said treatment.

[0135]

[0139] The Clinical Global Impression-Severity (CGI-C) scale is used by clinicians to assess symptom change in individuals with ASD. Individuals are assigned a score from 1 (much improved) to 7 (much worsened).

[0136]

[0140] In some embodiments, after said treatment, the patient experiences a reduction in symptoms associated with ASD, characterized by a decrease of at least one point on the CGI-C scale. In some embodiments, after said treatment, the patient experiences an improvement in irritability, characterized by a CGI-C score of 1 or less, 2 or less, 3 or less, or 4 or less. In some embodiments, after said treatment, the patient experiences an improvement in irritability, characterized by a Clinical Global Impression-Change (CGI-C) score of 3 or less. In some embodiments, after said treatment, the patient experiences an improvement in social skills, characterized by a CGI-C score of 1 or less, 2 or less, 3 or less, or 4 or less. In some embodiments, after said treatment, the patient experiences an improvement in social skills, characterized by a CGI-C score of 3 or less.

[0137]

[0141] The Autism Behavior Inventory (ABI) Social Deficits subscale is a scale used to assess change in core and associated symptoms of ASD. Individuals are administered the ABI-Full (93 items) or ABI-Condensed (36 items) scale. For each item on this scale, individuals are assigned a score from 0 to 6, where 0 is no symptoms and 6 is maximum symptoms. Individuals who score 0 exhibit no symptoms. Individuals assigned a score of 6 exhibit severe ASD symptoms.

[0138]

[0142] In some embodiments, the patient experiences an improvement in symptoms characterized by a decrease in ABI score of at least 1 point, hi some embodiments, the patient experiences an improvement in symptoms characterized by a decrease in ABI score of at least 1 point, or at least 2 points, or at least 3 points, or at least 4 points compared to before said treatment.

[0139]

[0143] In some embodiments, the patient experiences improvement in symptoms characterized by a reduction in ABI score of at least 5%, or at least 10%, or at least 15%, or at least 20%, or at least 25%, or at least 30%, or at least 35%, or at least 40%, or at least 45%, or at least 50%, or at least 55%, or at least 60%, or at least 65%, or at least 70%, or at least 75%, or at least 80%, or at least 85%, or at least 90%, or at least 95% compared to before said treatment.

[0140]

[0144] The Childhood Autism Rating Scale (CARS) is used to identify children aged 2 years and older with ASD. The CARS consists of 14 domains assessing behaviors associated with ASD, with a 15th domain assessing the overall impression of autism. Each domain is scored on a scale ranging from 1 to 4; higher scores are associated with greater levels of impairment. Total scores can range from a low of 15 to a high of 60; a score below 30 indicates the individual does not fall within the autism spectrum, a score of 30 to 36.5 indicates mild to moderate autism, and a score of 37 to 60 indicates severe autism.

[0141]

[0145] In some embodiments, after said treatment, the patient experiences a reduction in symptoms associated with ASD, characterized by a reduction in the CARS total score of about 1 point, about 2 points, about 3 points, about 4 points, about 5 points, about 6 points, about 7 points, about 8 points, about 9 points, about 10 points, about 11 points, about 12 points, about 13 points, about 14 points, about 15 points, about 16 points, about 17 points, about 18 points, about 19 points, about 20 points, about 21 points, about 22 points, about 23 points, about 24 points, about 25 points, about 26 points, about 27 points, about 28 points, about 29 points, or about 30 points compared to before said treatment.

[0142]

[0146] In some embodiments, after said treatment, the patient experiences a reduction in symptoms associated with ASD characterized by a reduction in CARS total score of at least 5%, or at least 10%, or at least 15%, or at least 20%, or at least 25%, or at least 30%, or at least 35%, or at least 40%, or at least 45%, or at least 50%, or at least 55%, or at least 60%, or at least 65%, or at least 70%, or at least 75%, or at least 80%, or at least 85%, or at least 90%, or at least 95% compared to before said treatment.

[0143]

[0147] The Interpersonal Responsiveness Scale, Second Edition (SRS-2) is used to obtain efficient quantitative measures of various dimensions of interpersonal behavior, communication, and repetitive / stereotypic behaviors associated with ASD. According to the SRS-2, individuals are assigned a proxy total t-score based on the SRS-2. This score reflects the sum of responses to the 65 Interpersonal Responsiveness Scale questions and is an indicator of social skill severity across the autism spectrum. Individuals who score a proxy t-score higher than 76 receive a severe clinical diagnosis of ASD. A proxy t-score of 66-75 is associated with clinically significant, moderate impairment in reciprocal social behavior that leads to substantial impairment in daily social interactions. A proxy t-score of 60-65 indicates mild to moderate impairment in social interaction. If a patient exhibits a proxy t-score of 59 or less, the patient exhibits normal social interaction.

[0144]

[0148] In some embodiments, prior to administering a therapeutically effective amount of a triptan to a patient in need thereof, the patient in need thereof exhibits a proxy-reported total t-score of 66 or greater.

[0145]

[0149] In some embodiments, the patient experiences improvement in symptoms characterized by a reduction in proxy-version total t-score of at least 1 point, or at least 2 points, or at least 3 points, or at least 4 points, or at least 5 points, or at least 6 points, or at least 7 points, or at least 8 points, or at least 9 points, or at least 10 points, or at least 11 points, or at least 12 points, or at least 13 points, or at least 14 points, or at least 15 points, or at least 16 points, or at least 17 points, or at least 18 points, or at least 20 points, or at least 21 points, or at least 22 points, or at least 23 points, or at least 24 points, or at least 25 points compared to before said treatment.

[0146]

[0150] In some embodiments, the patient experiences improvement in symptoms characterized by a reduction in the proxy version of the SRS-2 total t-score of at least 5%, or at least 10%, or at least 15%, or at least 20%, or at least 25%, or at least 30%, or at least 35%, or at least 40%, or at least 45%, or at least 50%, or at least 55%, or at least 60%, or at least 65%, or at least 70%, or at least 75%, or at least 80%, or at least 85%, or at least 90%, or at least 95% compared to before said treatment.

[0147]

[0151] The Interpersonal Responsiveness Scale for Adults (SRS-A) is a tool to assess interpersonal responsiveness in adults. The SRS-A includes 65 items scored from 0 to 3. If an individual scores 0, the individual does not have symptoms. If an individual scores 3, the individual has severe symptoms. An SRS-A total score of 67 indicates that the individual has ASD. The maximum possible SRS-A total score is 195.

[0148]

[0152] In some embodiments, after the treatment, the patient experiences a reduction in symptoms associated with ASD, characterized by a decrease in SRS-A score of at least 1 point compared to before the treatment. In some embodiments, the patient experiences an improvement in social skills, characterized by a decrease in SRS-A score of at least 1 point. In some embodiments, the patient's SRS-A score decreases by about 1 point, or about 5 points, or about 10 points, or about 15 points, or about 20 points, or about 25 points, or about 30 points, or about 35 points after the treatment.

[0149]

[0153] In some embodiments, after said treatment, the patient exhibits a reduction in symptoms associated with ASD characterized by a reduction in SRS-A score of about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, or about 70% compared to before said treatment. In some embodiments, after said treatment, the patient exhibits a reduction in symptoms associated with ASD characterized by at least a 10% reduction in SRS-A score compared to before said treatment.

[0150]

[0154] In some embodiments, improvement in social skills is associated with about a 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, or about 50% reduction in SRS-A score compared to before said treatment.

[0151]

[0155] The Aberrant Behavior Checklist (ABC) is a behavioral rating scale used to rate individuals on five subscales: (1) irritability, agitation, and crying; (2) lethargy and withdrawal; (3) stereotypic behaviors; (4) hyperactivity and noncompliance; and (5) inappropriate speech. Individuals can be assessed on the ABC by any adult who knows them well. The ABC includes a 58-item questionnaire used to rate the five subscales. Each item on the 58-item questionnaire is rated from 0 to 3. A score of 0 indicates the absence of symptoms. A score of 3 indicates the individual has high severity of symptoms. Items within each subscale are summed to determine the subscale score. Possible subscale scores on the ABC range from 0 to 48, with higher subscores indicating behavioral disturbances.

[0152]

[0156] In some embodiments, after the treatment, the patient experiences a reduction in symptoms associated with ASD, characterized by a decrease of at least one point in the ABC Irritability, Agitation, and Crying (ABC-I) subscore. In some embodiments, after the treatment, the patient experiences a reduction in irritability, characterized by a decrease in the ABC-I Communication domain score compared to before the treatment.

[0153]

[0157] In some embodiments, the patient presents with an ABC-I score of 18 or greater prior to treatment.

[0154]

[0158] In some embodiments, after said treatment, the patient experiences a reduction in irritability characterized by a decrease in ABC-I domain score of about 2, about 4, about 6, about 8, about 10, about 15, about 20, about 25, or about 30 points compared to before said treatment. In some embodiments, the decrease in ABC-I domain score is about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, or about 95% compared to before said treatment.

[0155]

[0159] In some embodiments, after the treatment, the patient experiences a reduction in symptoms associated with ASD characterized by a decrease of at least one point in the ABC-Apathy and Withdrawal (ABC-LSW) subscore compared to before the treatment. In some embodiments, after the treatment, the patient experiences a reduction in apathy and withdrawal characterized by a decrease in the ABC-LSW Communication domain score compared to before the treatment.

[0156]

[0160] In some embodiments, the reduction in the ABC-LSW Communication Domain score compared to before said treatment is about 2 points, about 4 points, about 6 points, about 8 points, about 10 points, about 15 points, about 20 points, about 25 points, or about 30 points.

[0157]

[0161] In some embodiments, the reduction in the ABC-LSW Communication Domain score compared to before said treatment is about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, or about 95%.

[0158]

[0162] The Social Communication Questionnaire is a tool used by physicians to screen individuals with ASD. An individual's caregiver rates the individual on a scale of 0 to 39 for verbal individuals or 0 to 33 for nonverbal individuals. Individuals with ASD are characterized by a Social Communication Questionnaire score above 15.

[0159]

[0163] In some embodiments, after said treatment, the patient experiences a reduction in symptoms associated with ASD characterized by at least a 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% decrease in a social communication questionnaire scale compared to before said treatment.

[0160]

[0164] The Pervasive Developmental Disorders Behavior Inventory (PDDBI) is used to assess the effectiveness of ASD treatments. The PDDBI assesses both problem behaviors and appropriate social, language, and learning / memory skills. The PDDBI is divided into two behavioral dimensions: (a) Approach-Avoidance Problems, which assesses maladaptive behaviors, and (b) Receptive / Expressive Social Communication Skills, which assesses social communication skills. The Approach-Avoidance Problems dimension is subdivided into behavioral domains, including Sensory / Perceptual Approach Behavior, Ritual Behavior / Resistance to Change (RITUAL), Social Practical Problems (SOCPP), Semantic / Pragmatic Problems (SEMPP), Arousal Control Problems (AROUSE), Specific Fears (FEARS), and Aggression (AGG). The Receptive / Expressive Social Communication Skills (REXSCA), which assesses social communication skills, is subdivided into behavioral domains, including Social Approach Behavior (SOCAPP), Expressive Language (EXPRESS), and Learning, Memory, and Receptive Language (LMRL). Individuals receive a T-score for each domain and a composite score that is the sum of the scores for each domain. Individuals with ASD are assigned a T-score higher than 50.

[0161]

[0165] In some embodiments, the Pervasive Developmental Disorder Behavior Inventory (PDDBI) is utilized to characterize the reduction in symptoms associated with ASD provided by the methods of the present disclosure. In some embodiments, the patient exhibits a T-score of greater than 50 prior to said treatment. In some embodiments, after said treatment, the patient experiences a reduction in symptoms associated with ASD characterized by a decrease in the PDDBI of about 5%, or about 10%, or about 15%, or about 20%, or about 25%, or about 30%, or about 35%, or about 40%, or about 45%, or about 50%, or about 55%, or about 60%, or about 65%, or about 70%, or about 75%, or about 80%, or about 85%, or about 90%, or about 95% compared to before said treatment.

[0162]

[0166] The ATEC is a scale used to determine the effectiveness of ASD treatments. The ATEC is a one-page form designed to be completed by parents, teachers, or caregivers. The ATEC consists of four subtests: Speech / Verbal Communication, Social, Sensory / Cognitive Awareness, and Health / Physical / Behavior. Individuals are assigned a Speech / Verbal Communication subtest rating of 0-28. Individuals are assigned a Social subtest rating of 0-40. Individuals are assigned a Sensory / Cognitive Awareness subtest rating of 0-36. Individuals are assigned a Health / Physical / Behavior subtest rating of 0-75. Individuals' individual subsets are summed, allowing for a maximum score of 180.

[0163]

[0167] In some embodiments, after the treatment, the patient experiences a reduction in symptoms associated with ASD, characterized by a decrease in mean ATEC score compared to before the treatment. In some embodiments, after the treatment, the patient experiences an improvement in speech / verbal communication, characterized by a decrease in speech / verbal communication subtest rating compared to before the treatment. In some embodiments, after the treatment, the patient experiences an improvement in sociality, characterized by a decrease in social subtest rating compared to before the treatment. In some embodiments, after the treatment, the patient experiences an improvement in sensory / cognitive awareness, characterized by a decrease in sensory / cognitive awareness subtest rating compared to before the treatment. In some embodiments, after the treatment, the patient experiences an improvement in health / physical / behavioral, characterized by a decrease in health / physical / behavioral rating compared to before the treatment.

[0164]

[0168] In some embodiments, the patient exhibits a decrease of at least 1 point, or about 2 points, or about 3 points, or about 4 points, or about 5 points, or about 6 points, or about 7 points, or about 8 points, or about 9 points, or about 10 points, or about 11 points, or about 12 points, or about 13 points, or about 14 points, or about 15 points, or about 16 points, or about 17 points, or about 18 points, or about 19 points, or about 20 points on the social subsection of the ATEC compared to before said treatment. In some embodiments, the patient exhibits a decrease of at least 1 point on the social subsection of the ATEC compared to before said treatment.

[0165]

[0169] In some embodiments, the patient exhibits at least a 5%, or at least a 10%, or at least a 15%, or at least a 20%, or at least a 25%, or at least a 30%, or at least a 35%, or at least a 40%, or at least a 50% decrease on the social subsection of the ATEC compared to before said treatment, hi some embodiments, the patient exhibits at least a 10% decrease on the social subsection of the ATEC compared to before said treatment.

[0166]

[0170] An objective / performance-based assessment is utilized to measure the reduction in symptoms associated with ASD after administering a therapeutically effective amount of a triptan to a patient in need thereof. In some embodiments, the objective / performance-based assessment is selected from the group consisting of eye tracking of social stimuli, the Parental Engagement Rating Inventory (JERI), and Noldus Ethovision analysis. In some embodiments, eye tracking of social stimuli is utilized to characterize the reduction in symptoms associated with ASD resulting from the methods of the present disclosure. Patients with ASD exhibit significantly shorter eye contact than peers without ASD. Patients with ASD have greater difficulty finding and processing relevant social information when stimuli are presented more rapidly.

[0167]

[0171] PCIT provides a training method designed to help adults improve their parenting and language skills and to help children learn how to better manage their emotions. In some embodiments, the parent-child interaction task (PCIT) is used to improve relationships between caregivers and individuals with ASD. In some embodiments, PCIT helps reduce child behavior problems and improve communication and interaction skills within families. In some embodiments, children who participate in CPT develop higher self-esteem, experience less anger and frustration, improve social, organizational, and play skills, feel more secure and calm, and communicate more effectively.

[0168]

[0172] The Joint Engagement Ranking Inventory (JERI) is a tool used to measure early intervention goals for developmental disorders and delays, including ASD. The JERI is an 18-item inventory developed to measure relevant intervention goals, including disengagement, object engagement, joint engagement, routine, restricted, repetitive behaviors, attention to the caregiver, initiating communication, expressive language level and use, scaffolding, following, caregiver affect, fluency, and connectedness, and sharing routines and rituals. Individuals assessed using the JERI scale score from 1 to 7 for each item on the JERI inventory. A score of 7 is assigned to individuals with the most joint engagement. Individuals with no episodes of joint engagement are assigned a score of 1 on an item. Lower JERI scores correlate with ASD.

[0169]

[0173] In some embodiments, a reduction in ASD symptoms is associated with a lower JERI score compared to before treatment with the disclosed methods. In some embodiments, after the treatment, the patient experiences a reduction in symptoms associated with ASD, characterized by a lower JERI score compared to before treatment. In some embodiments, the JERI score is reduced by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, or about 70% compared to before treatment.

[0170]

[0174] The Ohio State University Autism Rating Scale (OARS-5) measures persistent social interaction impairments, restricted interests / activities and repetitive behaviors, and levels of social, academic, and community support (Hollway, JA, Arnold, LE, & Aman, MG (2017, September). OSU Autism Rating Scale - DSM-5 (OARS-5)). The OARS-5 was developed to provide three summary scores: (A) an autism symptom count (OARS-5 total score) based on a clinical interview; (B) a weighted mean severity score derived from the clinical interview based on the severity of autism symptoms; and (C) a disability index ranging from 0 to 9 based on the level of support needed due to the severity. The OARS-5 total score is equal to the OARS-5 social deficit subscale score plus the OARS-5 restricted interest pattern subscale score.

[0171]

[0175] The OARS-5 includes the following subscales: · Section A: Persistent social interaction impairment across multiple settings (OARS-5 Social Deficits subscale score); Section B: Restricted Interests / Activities and Repetitive Behavior Patterns (OARS-5 Restricted Interest Patterns subscale score) and Section C: Level of support for sections A (social interaction / communication) and B (restricted repetitive behaviors).

[0172]

[0176] In some embodiments, after the treatment, the patient experiences a reduction in symptoms associated with ASD characterized by a decrease in the OARS-5 total score compared to before the treatment. In some embodiments, after the treatment, the patient experiences a reduction in symptoms associated with ASD characterized by a decrease in the OARS-5 total score of about 1 point, about 2 points, about 3 points, or about 4 points, about 5 points, about 6 points, about 7 points, about 8 points, about 9 points, or about 10 points compared to before the treatment.

[0173]

[0177] In some embodiments, after the treatment, the patient experiences a reduction in symptoms associated with ASD characterized by a decrease in OARS-5 Social Deficit subscale score compared to before the treatment. In some embodiments, after the treatment, the patient experiences a reduction in symptoms associated with ASD characterized by a decrease in OARS-5 Social Deficit subscale score of about 1 point, about 2 points, about 3 points, or about 4 points, about 5 points, about 6 points, about 7 points, about 8 points, or about 9 points compared to before the treatment.

[0174]

[0178] In some embodiments, after the treatment, the patient experiences a reduction in symptoms associated with ASD, as characterized by a lower Ohio State University Autism Clinical Global Impression (OSU Autism CGI) total score compared to before the treatment. The OSU Autism CGI-S total score is equal to the OSU Autism CGI-Severity Scale (OSU Autism CGI-S) score plus the OSU Autism CGI-Improvement Scale (OSU Autism CGI-I) score.

[0175]

[0179] In some embodiments, after said treatment, the patient experiences a reduction in symptoms associated with ASD, characterized by a decrease in the OSU Autism CGI total score of about 1 point, about 2 points, about 3 points, or about 4 points, about 5 points, about 6 points, or about 7 points compared to before treatment.

[0176]

[0180] In some embodiments, after the treatment, the patient experiences a reduction in symptoms associated with ASD, characterized by a decrease in the Ohio State University Autism Clinical Global Impression-Improvement (OSU Autism CGI-I) score compared to before the treatment. In some embodiments, after the treatment, the patient experiences a reduction in symptoms associated with ASD, characterized by a decrease of about 1, about 2, about 3, or about 4, about 5, about 6, or about 7 points on the OSU Autism CGI-I compared to before the treatment.

[0177]

[0181] In some embodiments, after the treatment, the patient experiences a reduction in symptoms associated with ASD, characterized by a lower Ohio State University Autism Clinical Global Impression-Severity Scale (OSU Autism CGI-S) score compared to before the treatment. In some embodiments, after the treatment, the patient experiences a reduction in symptoms associated with ASD, characterized by a reduction of about 1, about 2, about 3, or about 4, about 5, about 6, or about 7 points on the OSU Autism CGI-S compared to before the treatment.

[0178] Patient population

[0182] In some embodiments, the present disclosure provides a method of treating symptoms associated with autism spectrum disorder (ASD), comprising administering a therapeutically effective amount of a triptan to a patient in need thereof.

[0179]

[0183] In some embodiments, the patient in need of treatment for ASD is a patient diagnosed with ASD according to DSM-5 diagnostic criteria.

[0180]

[0184] In some embodiments, prior to treatment according to the methods of the present disclosure, an ASD patient in need thereof has a full-scale IQ score of 70 or greater on the Weschsler Abbreviated Scale of Intelligence (WASI®)-II.

[0181]

[0185] In some embodiments, the present disclosure provides a method for treating symptoms associated with ASD that are refractory to treatment with existing ASD treatments.In some embodiments, the symptoms associated with ASD are refractory to treatment with aripiprazole.In some embodiments, the symptoms associated with ASD are refractory to treatment with risperidone.

[0182]

[0186] In some embodiments, the ASD patient being treated exhibits atypical sensory processing. Sensory processing refers to the ability to register, process, and organize sensory information and to implement appropriate responses to environmental demands, which manifests as hypersensitivity or hyposensitivity to stimuli. A patient in need with atypical sensory processing may have an aversion to the color, taste, smell, and / or texture of food or medicine. In some embodiments, atypical sensory processing manifests in a patient in need as non-compliance with prescribed medication. In some embodiments, the ASD patient being treated refuses to swallow prescribed medication. In some embodiments, the prescribed medication is a liquid formulation or a pill.

[0183]

[0187] In some embodiments, the ASD patient being treated is an infant. In some embodiments, the ASD patient being treated is a child. In some embodiments, the ASD patient being treated is an adolescent. In some embodiments, the ASD patient being treated is an adult. In some embodiments, the ASD patient being treated is an elderly patient. [Example]

[0184] Example

[0188] The present disclosure is further illustrated by reference to the following examples, however, it is noted that these examples, like the embodiments described above, are illustrative and should not be construed as limiting the scope of the invention in any way.

[0185]

[0189] General Protocol

[0190] In mouse pharmacokinetic studies, the plasma Cmax of zolmitriptan occurred at the first measured time point (i.e., Tmax of 15 minutes). The Tmax of IP injection of naratriptan, rizatriptan, frovatriptan, and eletriptan also occurred at 15 minutes (i.e., the first measured time point in these studies).

[0186] Example 1

[0191] The effect of zolmitriptan on aggressive behavior was investigated in a mouse model.

[0187]

[0192] The rodent resident-intruder assay (RI) was used to monitor aggressive behavior in relation to behavioral patterns exhibited in territory establishment and defense (Miczek et al., 1984). Correspondingly, this RI assay has been used preclinically to study the effects of drugs on rodent aggression (Miczek et al., 2001). RI assays typically rely on the interpretation and scoring of aggressive (resident animal) behavioral patterns and may also include analysis of defensive (intruder animal) behavioral patterns.

[0188]

[0193] Aggressive behavior was assessed using unfamiliar, naive, age-matched "intruder" C57BL / 6 mice placed in the home cages of "resident" male BALB / c mice at least 8 weeks old and allowed to interact for 5 min. Throughout the study, resident mice were quarantined for 1 week before testing for aggressive behavior, while intruders were group-housed (4 mice per cage). All mice had free access to food and water.

[0189]

[0194] After a 1-week isolation period, aggressive behavior was recorded daily (Monday–Friday) using a front-facing camera for up to 2 weeks until a stable baseline was reached before determining drug effects. Borris open-source event logging software was used to score interactions, scoring the total number of aggressions initiated by the resident and the cumulative duration of those aggressions. If a fight lasted longer than 60 seconds, the fight was terminated, followed by removal of the intruder from the resident cage. Additionally, if the intruder displayed aggressive behavior, recording was stopped and the intruder was removed from the resident cage.

[0190]

[0195] The effects of 3 and 10 mg / kg zolmitriptan on aggression were determined using a BALB / c-C57BL / 6 RI combination. Resident mice were treated with vehicle for two consecutive days and then weighed for a two-arm (3 and 10 mg / kg) crossover study. On day 3, mice (n=10) were treated with 3 mg / kg, and n=10 mice received 10 mg / kg zolmitriptan. Following consecutive vehicle treatments on days 4 and 5, day 6 was the final day of crossover treatment. The pretreatment period was 15 minutes, and the drug was delivered by intraperitoneal (ip) injection.

[0191]

[0196] Results: As shown in Figures 1 and 2, BALB / c mice showed a reduction in the number and duration of attacks with zolmitriptan treatment. After the crossover study was completed, a significant dose-dependent effect of zolmitriptan treatment in reducing aggressive behavior was observed (p<0.05, paired t-test). In addition, zolmitriptan doses of 3 and 10 mg / kg had no effect on the normal locomotor activity of treated mice.

[0192] Example 2

[0197] Using the CD-1-C57BL / 6 combination, the effect of zolmitriptan (10 mg / kg) on ​​aggressive behavior in CD-1 mice was determined using a rodent RI assay, which was performed using the protocol described in Example 1. Risperidone (0.3 mg / kg) was used as a control compound. Aggression latency was measured over a 5-minute period in a crossover design.

[0193]

[0198] Zolmitriptan administered at 3 and 10 mg / kg (ip) produced Cmax values ​​of 5.40 and 34.42 ng / ml, respectively, in the CSF of adult male CD-1 mice. N-desmethylzolmitriptan ("NDMZ," the primary metabolite of zolmitriptan found in humans) was below the lower limit of quantitation in male CD-1 mice administered at 3 and 10 mg / kg (ip). Results: As shown in Figure 3 (and summarized in the table below), CD-1 mice treated with zolmitriptan at 10 mg / kg showed a significant reduction in attack time (seconds) compared to risperidone (0.03 mg / kg) and vehicle controls.

[0194] [Table 1]

[0195] Example 3

[0199] We investigated the effects of zolmitriptan in a mouse model of valproic acid-induced autism spectrum disorder (VPA) (Nicolini C et al., 2018 Exp. Neurol., 2018, 217-227; Bey AL, and Jiang J. H, Current Protocols in Pharmacology, 01 Sep 2014, 66:5.66.1-26). Specifically, sociality was assessed in male C57 / Bl6 mice pre-exposed to VPA via intraperitoneal delivery of 500 mg / kg VPA to pregnant mothers at day 13 post-fertilization.

[0196]

[0200] In this study, zolmitriptan was dissolved in 10% (2-hydroxypropyl)-β-cyclodextrin in saline and administered intraperitoneally (i.p.) 15 min before placing mice in the test chamber. Behavioral recordings were measured using an automated video tracking system (Noldus EthoVision v14) and analyzed and graphed using GraphPad Prism software v8. Sociality was assessed over a 10-min period in a three-chamber social interaction assay. The sociality score for each individual mouse was calculated using the time spent (in seconds) in the empty interaction zone (EIZ) and the social interaction zone (SIZ) in front of a juvenile, novel C57 / BL6 rat. The sociality index was calculated using the ratio SIZ / EIZ. Social interaction preference was calculated using (SIZ) / (SIZ + EIZ) × 100. Simultaneous recordings from up to four arenas were performed for this social interaction assay. Paired and unpaired t-tests were used as statistical tests.

[0197]

[0201] Zolmitriptan administered at 10 mg / kg (ip) produced a Cmax value (15 min post-dose) of 17.83 ng / ml in the CSF of adult male c57 / B16 mice (i.e., the Tg2576 background strain and the strain used for VPA treatment). NDMZ was below the lower limit of quantitation in the CSF of male c57 / B16 mice administered at 10 mg / kg (ip).

[0198]

[0202] As shown in Figure 4, zolmitriptan administered at 10 mg / kg (ip) increased the social index in adult male C57 / B16 mice pre-exposed to valproic acid (VPA). The improvement in sociality in zolmitriptan-treated mice was statistically significant compared to the vehicle-treated group.

[0199] Example 4

[0203] A study was conducted to assess the safety, tolerability, and pharmacokinetic response of oral zolmitriptan after multiple ascending doses in healthy adult volunteers.

[0200]

[0204] Zolmitriptan 2.5 mg or placebo tablets were administered three times daily (TID) during the titration period, the 7-day treatment period, and the titration period. The dosing regimen is shown in Table 1.

[0201] [Table 2]

[0202]

[0205] A lumbar puncture was performed for each subject to determine the concentration of zolmitriptan in the CSF. CSF samples were collected on day 5 of treatment for Cohort 1, day 7 of treatment for Cohorts 2 and 3, and day 8 of treatment for Cohorts 4 and 5. CSF collection was 2 hours (±30 minutes) after the morning dose. CSF concentrations were measured using a validated bioanalytical method. Results: As shown in Figure 5, CSF levels measured in humans were in a ratio of zolmitriptan:NDMZ = 1.0:0.75. Overall, zolmitriptan was safe and well tolerated in all cohorts.

[0203] Example 5.

[0206] Human PK studies correlating oral zolmitriptan dose administration with CSF concentrations (Example 4, i.e., mg of zolmitriptan administered with CSF Cmax achieved), effective CSF concentrations determined from the valproic acid ASD mouse model (Example 3), and species-specific binding assay data (human and mouse) were used to estimate an effective human dose for treating ASD symptoms with zolmitriptan.

[0204]

[0207] Specifically, the 5-HT1b receptor occupancy and efficacy model measured the potency of zolmitriptan and NDMZ at the 5-HT1b receptor and the zolmitriptan:NDMZ ratio in human CSF. The 5-HT1b receptor efficacy model was used to predict the level of 5-HT1b activation (i.e., efficacy) by both zolmitriptan and NDMZ based on the concentration of zolmitriptan in CSF (Table 5, column 2). This allowed the calculation of the target zolmitriptan dose range required to achieve effective CSF exposure in humans (Table 5, column 3). Those skilled in the art can apply similar methods to determine effective doses for treating ASD symptoms with the triptans described herein.

[0205] 35S-GTPγS binding assay

[0208] In this study, in vitro binding assays were performed to measure the affinities of zolmitriptan, its active metabolite NDMZ, eletriptan, naratriptan, and rizatriptan for rat and human 5-HT1B receptors.

[0206]

[0209] Zolmitriptan, eletriptan, naratriptan, and rizatriptan were tested in duplicate in an SPA-based 35S-GTPγS binding assay in cells expressing human 5-HT1b (h5-HT1b) receptors or rat recombinant 5-HT1b (r5-HT1b) receptors at 10 concentrations. EC50 values ​​are shown in Table 2.

[0207] [Table 3]

[0208]

[0210] All triptans exhibited lower apparent affinities (i.e., EC50) at rat 5-HT1b receptors than at human 5-HT1b receptors. In the case of zolmitriptan, the difference between species is 8.3-fold.

[0209]

[0211] The mouse and rat orthologues of 5-HT1b are 98% identical. They differ by only two amino acids, both of which are conservative changes that are outside the agonist-binding pocket (i.e., mouse / rat E152D in intracellular loop 1 and mouse / rat M192V in extracellular loop 2).

[0210]

[0212] Based on this data, the CSF levels required for zolmitriptan to produce a therapeutic effect in humans are approximately 8.3 times lower than those required for comparable activity in mice.

[0211]

[0213] Assuming that CSF values ​​reflect free drug concentrations in the brain, the estimated effective Cmax CSF value can be expressed as: CD-1 (mouse aggression model, Example 2); 3 mg / Kg (ip); CSF Cmax = 18.8 nM or EC36 (36% activity in GTPgS) c57 / B16 (ASD mouse model, Example 3); 10 mg / kg (ip); CSF Cmax = 62 nM EC65 (65% activity in GTPgS)

[0212] Radioligand binding competition assay

[0214] The affinities of zolmitriptan, NDMZ (the active metabolite of zolmitriptan in humans), eletriptan, naratriptan, rizatriptan, and frovatriptan for the human 5-HT1B receptor were determined in duplicate using a radioligand binding competition assay with 10 concentrations of 3H-5-CT and recombinant human 5-HT1B receptors. The affinities of the test compounds for the 5-HT1B receptor are shown in Table 3. Ki values ​​were calculated from the IC50 values ​​using the Cheng-Prusoff equation.

[0213] [Table 4]

[0214] 5-HT1b Receptor Occupancy and Efficacy Model

[0215] Using classical receptor theory, receptor occupancy when considering two ligands (i.e., entities) can be predicted using the following relationship: % Total Occupancy = (% Occupancy by A) + {[100% - (% Occupancy by A)] x (% Occupancy by B)}, where A and B are both considered to be constant concentrations.

[0215]

[0216] Given that the zolmitriptan:NDMZ ratio in humans is 1.0:0.75 in human CSF (FIG. 5), and that NDMZ is 2.83-fold more potent than zolmitriptan, a model for 5-HT1b occupancy was constructed using the % total occupancy equation above as a basis. This model was transformed to predict the level of 5-HT1b activation (i.e., efficacy) by both zolmitriptan and NDMZ based on the zolmitriptan concentration in CSF by substituting efficacy for occupancy as predicted by Clark's equation {efficacy = [L] / ([L]+Ki); [L] = ligand concentration} for both zolmitriptan and NDMZ: % Total Efficacy = {[zolmitriptan] / ([zolmitriptan] + Ki,Z)} + (100 - {[zolmitriptan] / ([zolmitriptan] + Ki,Z)} × {[NDMZ] / ([NDMZ] + Ki,N)}

[0216]

[0217] Using the measured EC50 value of zolmitriptan in the GTPgS assay, the 2.83-fold higher affinity of NMDZ for the human 5-HT1b receptor, and the measured relationship of zolmitriptan:NDMZ = 1.0:0.75, % total efficacy was calculated for a range of zolmitriptan concentrations, and the resulting % total efficacy predictions were fitted with a logistic equation:

[0217]

[0218] % Total Efficacy = 100 / (1 + 10^((LogEC50-[zolmitriptan]))) and Log EC50 is calculated as -8.963. The predicted concentration of zolmitriptan in human CSF that would produce 50% efficacy of 5-HT1b by zolmitriptan and NDMZ (i.e., EC50) is 1.09 nM or 0.31 ng / ml.

[0218]

[0219] The zolmitriptan concentration required to achieve 50% total efficacy is 3.7 times the zolmitriptan EC50 due to the combined effects of potent metabolites.

[0219]

[0220] Zolmitriptan Human Dose Ranges Across a range of 5-HT1b activity, as shown in Table 4, the doses required to achieve the predicted effective CSF concentration range in humans are determined.

[0220] [Table 5]

[0221] Dosage estimates for other triptans The CSF:plasma ratio for zolmitriptan exposure in humans is 3.0% (vs. 0.76% in mice). There is no evidence that other triptans exhibit this species-specific bias.

[0222] Dose predictions can be made based on the 5-HT1b EC50 and mouse CSF Cmax of each of the other triptans and by relating them to the zolmitriptan values ​​(Tables 3 and 5). Although the other triptans are not expected to produce as potent an active metabolite (i.e., NMDZ) as zolmitriptan, the contribution of any possible active metabolites for the other triptans can be derived using 5-HT1b receptor occupancy and efficacy models similar to those disclosed herein for zolmitriptan.

[0223] [Table 6]

[0224] Incorporation by Reference All references, articles, publications, patents, patent publications, and patent applications cited herein are incorporated by reference in their entirety for all purposes. However, reference to any reference, article, publication, patent, patent publication, or patent application cited herein is not, and should not be construed as, an admission or any form of suggestion that they constitute prior art or form part of the common general knowledge in any country in the world.

[0225] Embodiment 1. A method for treating symptoms associated with autism spectrum disorder (ASD), comprising administering a therapeutically effective amount of a triptan to a patient in need thereof. 2. The method of embodiment 1, wherein prior to said treatment, said patient has been diagnosed with ASD using DSM-5 diagnostic criteria. 3. The method of embodiment 1 or 2, wherein prior to said treatment, said patient has an Aberrant Behavior Checklist Irritability Subscale (ABC-I) score of 18 or greater. 4. The method of any one of embodiments 1 to 3, wherein prior to said treatment, said patient has a Social Responsiveness Scale, Second Edition (SRS-2), Proxy Version total t-score of 66 or greater. 5. The method of any one of embodiments 1-4, wherein prior to said treatment, said patient has a full-scale IQ score of 70 or greater on the Wechsler Abbreviated Scale of Intelligence (WASI®)-II. 6. The method of any one of embodiments 1-5, wherein prior to said treatment, said patient has severe irritability and / or aggression. 7. The method of any one of embodiments 1-6, wherein prior to said treatment, said patient has moderate irritability and / or aggression. 8. The method of any one of embodiments 1-7, wherein prior to said treatment, said patient has moderate lethargy and / or social deficits. 9. The method of any one of embodiments 1-8, wherein the patient's condition is refractory to treatment with aripiprazole and risperidone. 10. The method of any one of embodiments 1-9, wherein the patient is an adolescent. 11. The method of any one of embodiments 1-9, wherein the patient is a child. 12. The method of any one of embodiments 1-9, wherein the patient is an adult. 13. The method of any one of embodiments 1-12, wherein the triptan is selected from the group consisting of sumatriptan, zolmitriptan, naratriptan, rizatriptan, almotriptan, frovatriptan, eletriptan, donitriptan, and avitriptan, or a pharmaceutically acceptable salt thereof. 14. The method of any one of embodiments 1-13, wherein the triptan is administered orally. 15. The method of any one of embodiments 1-13, wherein the triptan is administered intranasally. 16. The method of any one of embodiments 1-13, wherein the triptan is administered subcutaneously. 17. The method of any one of embodiments 1-16, wherein the triptan is administered once daily. 18. The method of any one of embodiments 1-16, wherein the triptan is administered twice daily. 19. The method of any one of embodiments 1-16, wherein the triptan is administered three times a day. 20. The method of any one of embodiments 1-19, wherein the triptan is sumatriptan or a pharmaceutically acceptable salt thereof. 21. The method of any one of embodiments 1-20, wherein the triptan is sumatriptan hydrochloride. 22. The method of any one of embodiments 1-20, wherein the triptan is sumatriptan succinate. 23. The method of any one of embodiments 1-16 and 20-22, wherein about 3 mg of sumatriptan is administered once daily. 24. The method of any one of embodiments 1-16 and 20-22, wherein about 3 mg of sumatriptan is administered twice daily. 25. The method of any one of embodiments 1-16 and 20-22, wherein about 3 mg of sumatriptan is administered three times a day. 26. The method of any one of embodiments 1-16 and 20-22, wherein about 3 mg of sumatriptan is administered four times a day. 27. The method of any one of embodiments 1-16 and 20-22, wherein about 6 mg of sumatriptan is administered once daily. 28. The method of any one of embodiments 1-16 and 20-22, wherein about 6 mg of sumatriptan is administered twice daily. 29. The method of any one of embodiments 1-16 and 20-22, wherein about 5 mg of sumatriptan is administered once daily. 30. The method of any one of embodiments 1-16 and 20-22, wherein about 5 mg of sumatriptan is administered twice daily. 31. The method of any one of embodiments 1-16 and 20-22, wherein about 10 mg of sumatriptan is administered once a day. 32. The method of any one of embodiments 1-16 and 20-22, wherein about 10 mg of sumatriptan is administered twice daily. 33. The method of any one of embodiments 1-16 and 20-22, wherein about 10 mg of sumatriptan is administered three times a day. 34. The method of any one of embodiments 1-16 and 20-22, wherein about 20 mg of sumatriptan is administered once a day. 35. The method of any one of embodiments 1-16 and 20-22, wherein about 20 mg of sumatriptan is administered twice daily. 36. The method of any one of embodiments 1-16 and 20-22, wherein about 22 mg of sumatriptan is administered once daily. 37. The method of any one of embodiments 1-16 and 20-22, wherein about 22 mg of sumatriptan is administered twice daily. 38. The method of any one of embodiments 1-16 and 20-22, wherein about 25 mg of sumatriptan is administered once a day. 39. The method of any one of embodiments 1-16 and 20-22, wherein about 25 mg of sumatriptan is administered twice daily. 40. The method of any one of embodiments 1-16 and 20-22, wherein about 50 mg of sumatriptan is administered once daily. 41. The method of any one of embodiments 1-16 and 20-22, wherein about 50 mg of sumatriptan is administered twice daily. 42. The method of any one of embodiments 1-16 and 20-22, wherein about 100 mg of sumatriptan is administered once daily. 43. The method of any one of embodiments 1-16 and 20-22, wherein about 100 mg of sumatriptan is administered twice daily. 44. The method of any one of embodiments 1-19, wherein the triptan is zolmitriptan or a pharmaceutically acceptable salt thereof. 45. The method of any one of embodiments 1-16 and 44, wherein about 1.25 mg of zolmitriptan is administered once daily. 46. ​​The method of any one of embodiments 1-16 and 44, wherein about 1.25 mg of zolmitriptan is administered twice daily. 47. The method of any one of embodiments 1-16 and 44, wherein about 1.25 mg of zolmitriptan is administered three times a day. 48. The method of any one of embodiments 1-16 and 44, wherein about 2.5 mg of zolmitriptan is administered once daily. 49. The method of any one of embodiments 1-16 and 44, wherein about 2.5 mg of zolmitriptan is administered twice daily. 50. The method of any one of embodiments 1-16 and 44, wherein about 2.5 mg of zolmitriptan is administered three times daily. 51. The method of any one of embodiments 1-16 and 44, wherein about 5 mg of zolmitriptan is administered once a day. 52. The method of any one of embodiments 1-16 and 44, wherein about 5 mg of zolmitriptan is administered twice daily. 53. The method of any one of embodiments 1-16 and 44, wherein about 5 mg of zolmitriptan is administered three times a day. 54. The method of any one of embodiments 1-16 and 44, wherein about 7.5 mg of zolmitriptan is administered once daily. 55. The method of any one of embodiments 1-16 and 44, wherein about 7.5 mg of zolmitriptan is administered twice daily. 56. The method of any one of embodiments 1-16 and 44, wherein about 7.5 mg of zolmitriptan is administered three times a day. 57. The method of any one of embodiments 1-16 and 44, wherein about 10 mg of zolmitriptan is administered once a day. 58. The method of any one of embodiments 1-16 and 44, wherein about 10 mg of zolmitriptan is administered twice daily. 59. The method of any one of embodiments 1-16 and 44, wherein about 10 mg of zolmitriptan is administered three times a day. 59a. The method of any one of embodiments 1-16 and 44, wherein about 12.5 mg of zolmitriptan is administered once daily. 59b. The method of any one of embodiments 1-16 and 44, wherein about 12.5 mg of zolmitriptan is administered twice daily. 59c. The method of any one of embodiments 1-16 and 44, wherein about 12.5 mg of zolmitriptan is administered three times daily. 59d. The method of any one of embodiments 1-16 and 44, wherein about 15 mg of zolmitriptan is administered once daily. 59e. The method of any one of embodiments 1-16 and 44, wherein about 15 mg of zolmitriptan is administered twice daily. 59f. The method of any one of embodiments 1-16 and 44, wherein about 15 mg of zolmitriptan is administered three times daily. 59 g. The method of any one of embodiments 1-16 and 44, wherein about 17.5 mg of zolmitriptan is administered once daily. 59h. The method of any one of embodiments 1-16 and 44, wherein about 17.5 mg of zolmitriptan is administered twice daily. 59i. The method of any one of embodiments 1-16 and 44, wherein about 17.5 mg of zolmitriptan is administered three times daily. 59j. The method of any one of embodiments 1-16 and 44, wherein about 20 mg of zolmitriptan is administered once daily. 59k. The method of any one of embodiments 1-16 and 44, wherein about 20 mg of zolmitriptan is administered twice daily. 591. The method of any one of embodiments 1-16 and 44, wherein about 20 mg of zolmitriptan is administered three times daily. 59m. The method of any one of embodiments 1-16 and 44, wherein about 25 mg of zolmitriptan is administered once daily. 59n. The method of any one of embodiments 1-16 and 44, wherein about 25 mg of zolmitriptan is administered twice daily. 59o. The method of any one of embodiments 1-16 and 44, wherein about 25 mg of zolmitriptan is administered three times daily. 59p. The method of any one of embodiments 1-16 and 44, wherein about 30 mg of zolmitriptan is administered once daily. 59q. The method of any one of embodiments 1-16 and 44, wherein about 30 mg of zolmitriptan is administered twice daily. 59r. The method of any one of embodiments 1-16 and 44, wherein about 30 mg of zolmitriptan is administered three times daily. 59s. The method of any one of embodiments 1-16 and 44, wherein about 35 mg of zolmitriptan is administered once daily. 59t. The method of any one of embodiments 1-16 and 44, wherein about 35 mg of zolmitriptan is administered twice daily. The method of any one of embodiments 1-16 and 44, wherein about 35 mg of zolmitriptan is administered three times daily. 59v. The method of any one of embodiments 1-16 and 44, wherein about 40 mg of zolmitriptan is administered once daily. 59w. The method of any one of embodiments 1-16 and 44, wherein about 40 mg of zolmitriptan is administered twice daily. 59x. The method of any one of embodiments 1-16 and 44, wherein about 40 mg of zolmitriptan is administered three times daily. 59y. The method of any one of embodiments 1-16 and 44, wherein about 45 mg of zolmitriptan is administered once daily. 59z. The method of any one of embodiments 1-16 and 44, wherein about 45 mg of zolmitriptan is administered twice daily. 59a'. The method of any one of embodiments 1-16 and 44, wherein about 45 mg of zolmitriptan is administered three times daily. 60. The method of any one of embodiments 1-19, wherein the triptan is naratriptan or a pharmaceutically acceptable salt thereof. 61. The method of any one of embodiments 1-19 and 60, wherein the triptan is naratriptan hydrochloride. 62. The method of any one of embodiments 1-16 and 60-61, wherein about 1 mg of naratriptan is administered once daily. 63. The method of any one of embodiments 1-16 and 60-62, wherein about 1 mg of naratriptan is administered twice daily. 64. The method of any one of embodiments 1-16 and 60-62, wherein about 2.5 mg of naratriptan is administered once daily. 65. The method of any one of embodiments 1-16 and 60-62, wherein about 2.5 mg of naratriptan is administered twice daily. 66. The method of any one of embodiments 1-19, wherein the triptan is rizatriptan or a pharmaceutically acceptable salt thereof. 67. The method of any one of embodiments 1-19 and 66, wherein the triptan is rizatriptan benzoate. 68. The method of any one of embodiments 1-16 and 66-67, wherein about 5 mg of rizatriptan is administered once daily. 69. The method of any one of embodiments 1-16 and 66-67, wherein about 5 mg of rizatriptan is administered twice daily. 70. The method of any one of embodiments 1-16 and 66-67, wherein about 10 mg of rizatriptan is administered once daily. 71. The method of any one of embodiments 1-16 and 66-67, wherein about 10 mg of rizatriptan is administered twice daily. 72. The method of any one of embodiments 1-16 and 66-67, wherein about 10 mg of rizatriptan is administered three times a day. 73. The method of any one of embodiments 1-19, wherein the triptan is almotriptan or a pharmaceutically acceptable salt thereof. 74. The method of any one of embodiments 1-19 and 73, wherein the triptan is almotriptan malate. 75. The method of any one of embodiments 1-16 and 73-74, wherein about 6.25 mg of almotriptan is administered once daily. 76. The method of any one of embodiments 1-16 and 73-74, wherein about 6.25 mg of almotriptan is administered twice daily. 77. The method of any one of embodiments 1-16 and 73-74, wherein about 12.5 mg of almotriptan is administered once daily. 78. The method of any one of embodiments 1-16 and 73-74, wherein about 12.5 mg of almotriptan is administered twice daily. 79. The method of any one of embodiments 1-19, wherein the triptan is frovatriptan or a pharmaceutically acceptable salt thereof. 80. The method of any one of embodiments 1-19 and 79, wherein the triptan is frovatriptan succinate. 81. The method of any one of embodiments 1-16 and 79-80, wherein about 2.5 mg of frovatriptan is administered once daily. 82. The method of any one of embodiments 1-16 and 79-80, wherein about 2.5 mg of frovatriptan is administered twice daily. 83. The method of any one of embodiments 1-16 and 79-80, wherein about 2.5 mg of frovatriptan is administered three times daily. 84. The method of any one of embodiments 1-19, wherein the triptan is eletriptan or a pharmaceutically acceptable salt thereof. 85. The method of any one of embodiments 1-19 and 84, wherein the triptan is eletriptan hydrobromide. 86. The method of any one of embodiments 1-16 and 84-85, wherein about 20 mg of eletriptan is administered once daily. 87. The method of any one of embodiments 1-16 and 84-85, wherein about 20 mg of eletriptan is administered twice daily. 88. The method of any one of embodiments 1-16 and 84-85, wherein about 40 mg of eletriptan is administered once daily. 89. The method of any one of embodiments 1-16 and 84-85, wherein about 40 mg of eletriptan is administered twice daily. 90. The method of any one of embodiments 1-89, wherein after said treatment, said patient experiences a substantial reduction in symptoms associated with ASD compared to before said treatment. 91. The method of any one of embodiments 1-90, wherein the patient exhibits a substantial improvement in sociality after said treatment compared to before said treatment. 92. The method of any one of embodiments 1-91, wherein after said treatment, the patient exhibits improved social skills as characterized by a decrease of at least one point on the social subsection of the Autism Treatment Evaluation Checklist (ATEC) compared to before said treatment. 93. The method of any one of embodiments 1 to 92, wherein after said treatment, the patient exhibits improved sociality characterized by at least a 10% decrease in the social subsection of the ATEC compared to before said treatment. 94. The method of any one of embodiments 1-93, wherein after said treatment, the patient exhibits improved social skills as characterized by at least a one-point decrease in the Social Interactions score on the Autism Diagnostic Observation Schedule, Module 4, compared to before said treatment. 95. The method of any one of embodiments 1-94, wherein after said treatment, the patient exhibits improved social skills characterized by at least a 10% decrease in Social Interaction score on the Autism Diagnostic Observation Schedule Module 4 compared to before said treatment. 96. The method of any one of embodiments 1 to 95, wherein after said treatment, the patient exhibits improved social skills characterized by a decrease of at least one point in the Social Responsiveness Scale (SRS-A) score compared to before said treatment. 97. The method of any one of embodiments 1 to 96, wherein after said treatment, the patient exhibits an improvement in social function characterized by at least a 10% decrease in SRS-A score compared to before said treatment. 98. The method of any one of embodiments 1 to 97, wherein after the treatment, the patient exhibits an improvement in social skills associated with ASD, characterized by a Clinical Global Impression-Change (CGI-C) score of 3 or less. 99. The method of any one of embodiments 1-98, wherein after said treatment, said patient exhibits a substantial decrease in irritability associated with ASD compared to before said treatment. 100. The method of any one of embodiments 1-99, wherein after said treatment, said patient exhibits an improvement in irritability associated with ASD, characterized by a decrease of at least one point in the ABC-I score, compared to before said treatment. 101. The method of any one of embodiments 1-100, wherein after said treatment, said patient experiences an improvement in irritability associated with ASD characterized by at least a 10% decrease in ABC-I score compared to before said treatment. 102. The method of any one of embodiments 1-101, wherein after said treatment, said patient experiences an improvement in irritability associated with ASD characterized by at least a 35% decrease in ABC-I score compared to before said treatment. 103. The method of any one of embodiments 1-102, wherein after the treatment, the patient shows improvement in irritability associated with ASD, characterized by a Clinical Global Impression-Change (CGI-C) score of 3 or less. 104. The method of any one of embodiments 1-103, wherein after said treatment, said patient experiences an improvement in symptoms of ASD characterized by at least a 10% improvement in the socialization domain score on the Vineland 3 Adaptive Behavior Scale compared to before said treatment. 105. The method of any one of embodiments 1-104, wherein after said treatment, said patient experiences an improvement in symptoms of ASD characterized by at least a 35% improvement in the socialization domain score on the Vineland 3 Adaptive Behavior Scale compared to before said treatment. 106. The method of any one of embodiments 1-105, wherein after said treatment, the patient experiences an improvement in symptoms of ASD characterized by at least a 10% improvement in the communication domain score on the Vineland 3 Adaptive Behavior Scale compared to before said treatment. 107. The method of any one of embodiments 1-106, wherein after said treatment, the patient experiences an improvement in symptoms of ASD characterized by at least a 35% improvement in the communication domain score on the Vineland 3 Adaptive Behavior Scale compared to before said treatment. 108. The method of any one of embodiments 1-107, wherein after said treatment, said patient experiences an improvement in symptoms of ASD as characterized by at least a 1-point improvement in the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) composite total score compared to before said treatment. 109. The method of any one of embodiments 1-108, wherein after said treatment, the patient experiences an improvement in symptoms of ASD characterized by a decrease of at least 1 point in the OARS-5 total score compared to before said treatment. 110. The method of any one of embodiments 1-109, wherein after said treatment, the patient experiences an improvement in symptoms of ASD characterized by at least a 1-point decrease in OARS-5 Social Deficit Subscale score compared to before said treatment. 111. The method of any one of embodiments 1 to 110, wherein after said treatment, the patient experiences an improvement in symptoms of ASD characterized by at least a 1-point decrease in the OSU Autism CGI total score compared to before said treatment. 112. The method of any one of embodiments 1 to 111, wherein after said treatment, the patient experiences an improvement in symptoms of ASD characterized by at least a 1-point decrease in OSU Autism CGI-I score compared to before said treatment. 113. The method of any one of embodiments 1-111, wherein after said treatment, the patient experiences an improvement in symptoms of ASD characterized by at least a 1-point decrease in OSU Autism CGI-S score compared to before said treatment.

Claims

1. 1. A pharmaceutical composition for use in reducing irritability or improving sociality associated with autism spectrum disorder (ASD) in a patient, the pharmaceutical composition comprising zolmitriptan or a pharmaceutically acceptable salt thereof.

2. The pharmaceutical composition described in claim 1, wherein the patient has been diagnosed with ASD using the DSM-5 diagnostic criteria.

3. A pharmaceutical composition described in claim 1 or 2, wherein the patient's Aberrant Behavior Checklist Irritability Subscale (ABC-I) score is 18 or higher.

4. The pharmaceutical composition described in claim 1 or 2, wherein the patient's total t-score on the Social Responsiveness Scale, Second Edition (SRS-2), proxy version, is 66 or greater.

5. The pharmaceutical composition described in claim 1 or 2, wherein the patient has a full-scale IQ score of 70 or greater on the Wechsler Abbreviated Intelligence Scale (WASI (registered trademark))-II.

6. A pharmaceutical composition described in claim 1 or 2, wherein the patient has severe or moderate irritability and / or aggressiveness.

7. A pharmaceutical composition described in claim 1 or 2, wherein the patient has lethargy and / or social deficiency.

8. 3. The pharmaceutical composition of claim 1 or 2, wherein the patient's condition is refractory to treatment with aripiprazole and risperidone.

9. The pharmaceutical composition of claim 1 or 2, wherein the patient is an adolescent.

10. The pharmaceutical composition of claim 1 or 2, wherein the patient is a child.

11. The pharmaceutical composition of claim 1 or 2, wherein the patient is an adult.

12. The pharmaceutical composition of claim 1 or 2, wherein the improvement in sociality associated with ASD is characterized by at least a 10% decrease in the social subsection of ATEC compared to before treatment.

13. The pharmaceutical composition of claim 1 or 2, wherein the improvement in ASD-associated sociality is characterized by at least a 10% decrease in social interaction score on the Autism Diagnostic Observation Schedule Module 4 compared to pre-treatment.

14. The pharmaceutical composition of claim 1 or 2, wherein the improvement in ASD-related sociality is characterized by at least a 10% decrease in SRS-A score compared to before treatment.

15. The pharmaceutical composition of claim 1 or 2, wherein the improvement in sociality associated with ASD is characterized by a Clinical Global Impression-Change (CGI-C) score of 3 or less.

16. The pharmaceutical composition of claim 1 or 2, wherein the reduction in irritability associated with ASD is characterized by at least a 10% decrease in ABC-I score compared to before treatment.

17. The pharmaceutical composition of claim 1 or 2, wherein the reduction in irritability associated with ASD is characterized by at least a 35% decrease in ABC-I score compared to before treatment.

18. The pharmaceutical composition of claim 1 or 2, wherein the reduction in irritability associated with ASD is characterized by a Clinical Global Impression-Change (CGI-C) score of 3 or less.

19. 3. The pharmaceutical composition of claim 1 or 2, wherein the reduction in irritability or improvement in sociality associated with ASD is characterized by at least a 10% improvement in the socialization domain score of the Vineland-3 Adaptive Behavior Scale compared to before treatment.

20. 3. The pharmaceutical composition of claim 1 or 2, wherein the reduction in irritability or improvement in sociality associated with ASD is characterized by at least a 10% improvement in the communication domain score of the Vineland-3 Adaptive Behavior Scales compared to pre-treatment.

21. 3. The pharmaceutical composition of claim 1 or 2, wherein the reduction in ASD-associated irritability or improvement in sociality is characterized by at least a 1-point improvement in the Autism Diagnostic Observation Scale, Second Edition (ADOS-2) composite total score compared to before treatment.

22. 3. The pharmaceutical composition of claim 1 or 2, wherein the reduction in ASD-associated irritability or improvement in sociability is characterized by a decrease of at least one point in the OARS-5 total score compared to before treatment.

23. 3. The pharmaceutical composition of claim 1 or 2, wherein the reduction in ASD-associated irritability or improvement in sociality is characterized by at least a 1-point decrease in the OARS-5 Social Deficit Subscale score compared to before treatment.

24. 3. The pharmaceutical composition of claim 1 or 2, wherein the reduction in irritability or improvement in sociality associated with ASD is characterized by at least a 1-point decrease in the OSU Autism CGI total score compared to before treatment.

25. 3. The pharmaceutical composition of claim 1 or 2, wherein the reduction in irritability or improvement in sociality associated with ASD is characterized by a decrease of at least one point in the OSU Autism CGI-I score compared to before treatment.

26. 3. The pharmaceutical composition of claim 1 or 2, wherein the reduction in irritability or improvement in sociality associated with ASD is characterized by a decrease of at least one point in the OSU Autism CGI-S score compared to before treatment.

27. The pharmaceutical composition of claim 1 or 2, wherein a dose range of 1.0 mg to 50 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is for administration to a patient.

28. 28. The pharmaceutical composition of claim 27, wherein the zolmitriptan or a pharmaceutically acceptable salt thereof is for once-daily administration.

29. 28. The pharmaceutical composition of claim 27, wherein said administration results in a CSF level range of zolmitriptan of 0.05 ng / mL to 2 ng / mL.

30. 28. The pharmaceutical composition of claim 27, wherein the administration reduces the patient's Aberrant Behavior Checklist-2 Irritability Subscale (ABC-I) subscore, ABC-Apathy and Withdrawn (ABC-LSW) subscore, Autism Behavior Inventory (ABI) score, ABI Repetitive / Restricted Behaviors domain score, ABI Mood and Anxiety domain score, ABI Challenging Behavior domain score, ABI Self-Regulation domain score, ABI-Shortened Version (ABI-S) score, Clinical Global Impression-Improvement (CGI-I) score, Clinical Global Impression-Severity scale (CGI-S) score, Social Responsiveness Scale-Second Edition (SRS-2) score, and / or Vineland-3 (Domain Level Version) score by at least 1 or 2 points compared to before treatment.

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