GEPIRONE TREATMENT OF ATYPICAL DEPRESSION - PRELIMINARY EVIDENCE OF SEROTONERGIC INVOLVEMENT

This is a report of a controlled trial of gepirone, a 5-hydroxytryptam ine (5-HT1A) partial agonist azapirone related to buspirone, in the tr eatment of atypical depression. The azapirones are of particular inter est because their highly selective actions on the serotonergic system may possibly make them useful pharmacologic probes and potentially sel ective therapeutic agents. Sixty outpatients meeting Columbia criteria for definite or probable atypical depression were enrolled in a doubl e-blind, randomized, placebo-controlled, 8-week clinical trial at a si ngle site. The dosage schedule was fixed flexible, with 10-mg capsules given on a thrice-daily schedule, with doses of up to 120 mg daily. T he response rate at 8 weeks for the intention-to-treat sample analyzed with the last observation carried forward was 62% (18 of 29 patients) for gepirone and 20% (6 of 30 patients) for placebo (X(2) = 9.1; df = 1; P < 0.001). Robust and consistent drug-placebo differences are see n across virtually all rating scales posttreatment. The effect of gepi rone was consistent across the levels of concomitant variables, includ ing duration of episode and presence of dysthymia or panic. Gepirone i s a novel antidepressant that holds promise for the treatment of atypi cal depression and that may be of heuristic value because of its relat ively specific actions on the serotonergic system.