Gepirone in Depression and Anxiety Disorders

Abstract

Gepirone is an azapirone derivative with partial agonist activity at the post-synaptic serotonin (5-hydroxytryptamine) 5-HT1A receptor. In contrast to buspirone, gepirone lacks appreciable in vitro affinity for the dopamine D2 receptor, and exhibits only limited dopaminergic activity in vivo. The drug is active in several animal models considered predictive of antidepressant and anxiolytic activity, and is currently under development as a potential treatment for affective and anxiety disorders. The limited number of controlled clinical trials performed to date indicate that gepirone is of superior therapeutic efficacy to placebo on short term (≤ 10 weeks) administration to outpatients with generalised anxiety disorder (dosage range ≤ 60 mg/day) and major depressive disorder or atypical depression (dosage range ≤ 90 mg/day). The antidepressant effect of gepirone appears to be additional to its anxiolytic effect. As with buspirone, onset of the anxiolytic effect of gepirone appears to be delayed (≈ 2 to 4 weeks) relative to that of the benzodiazepines. The tolerability profile of gepirone mirrors that of buspirone: gepirone is nonsedating, lacks anticholinergic effects, and appears to be of low abuse potential. Gepirone has a possible role in the treatment of major depression, particularly that of the milder, non-endogenous or non-melancholic subtype, major depression associated with generalised anxiety, atypical depression, and chronic generalised anxiety disorder.