Therapeutic Combinations for the Treatment or Prevention of Depression

Abstract

Therapeutic combinations useful in the treatment or prevention of depression or other mood disorders, to pharmaceutical compositions containing said combinations, and to their use in the treatment or prophylaxis of depression or other mood disorders are provided. Such compounds are of formula I:or a pharmaceutically acceptable salt thereof, wherein each of R1, R2, R3, n, y, and Ar are as defined and described herein.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to U.S. Provisional Patent Application Ser. No. 60 / 674,048, filed Apr. 22, 2005, the entirety of which is hereby incorporated herein by reference.FIELD OF THE INVENTION[0002]The present invention relates to therapeutic combinations of compounds useful for the treatment or prophylaxis of depression, to pharmaceutical compositions containing such combinations, and to their use in the treatment or prophylaxis of depression.BACKGROUND OF THE INVENTION[0003]Between 5-10% of adults worldwide suffer from depression. Even more experience depression-related mood disorders such as dysthymia, seasonal affective disorder, and postpartum depression, bipolar disorder, anxiety disorder, posttraumatic stress disorder, panic disorder, and obsessive-compulsive disorder.[0004]The economic costs to society, and person costs to individuals and families, associated with depression are enormous. Within a 15-month period after ha...

AI Technical Summary

Benefits of technology

[0088]Agents used in inventive combinations or compositions may be administered simultaneously, in the same or different pharmaceutical formulation, or sequentially. The timing of the sequential administration may desirably be selected to preserve the advantageous effects of the combination and said timing can be determined by a skilled practitioner. In other embodiments, the combinations are combined in a single unit dosage form.

[0089]A therapeutically effective amount of the combination will be understood to be an amount which treats, inhibits, prevents or ameliorates one or more symptoms of the depression or mood disorder in question. In certain embodiments of the invention, the combination will show improved efficacy as compared with that achieved by administration of the same amount of either the compound of formula I or the antidepressant agent alone. Furthermore, in certain embodiments, the effective amount of the combination produces fewer side effects than are observed when the antidepressant agent is administered alone at a dose that achieves substantially similar therapeutic efficacy.

[0090]The dosages of each of the drugs in the inventive combination may be determined by a physician and will often depend upon the specific circumstances of the depression or mood disorder, as well as the size, age and response pattern of the patient. Dosage guidelines are provided here. For the combination, the dosage guideline for each of the drugs of the combination would be considered.

[0091]In general, suitable doses of compound of formula I from about 0.5 mg per day to about 500 mg per day; in some embodiments from about 1 to about 500 mg per day.

[0092]A suitable dose of antidepressant agent may be in the range recommended by the manufacturer or reported in the literature. In some embodiments of the invention, the antidepressant agent is used at the low end of the range recommended by the manufacturer, or even below the range, in light of synergistic benefits that can be achieved according to the present invention. The following guidelines are provided for certain antidepressants useful in the practice of the present invention:

[0095]Citalopram: from about 5 to about 50 mg once / day; preferred, from about 10 to about 30 mg once / day;

Problems solved by technology

The economic costs to society, and person costs to individuals and families, associated with depression are enormous.

However, even with these options available, many patients fail to respond, or respond only partially to treatment.

Additionally, many of these agents show delayed onset of activity, so that patients are required to undergo treatment for weeks or months before receiving benefits.

Traditional therapies can also have significant side effects.

Other problematic side effects include gastrointestinal disturbances, often manifested as nausea and occasional vomiting, agitation, insomnia, weight gain, onset of diabetes, prolongation of the heart rate corrected interval (QTc), agranylocytosis, etc.

These side effects often discourage patients from following their recommended therapeutic regimen.

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