Sustained efficacy of gepirone-IR in major depressive disorder: a double-blind placebo substitution trial

The objective of this paper is to evaluate the efficacy of gepirone immediate-release (gepirone-IR) for relapse prevention in outpatients with MDD who had responded to initial gepirone-IR therapy. Patients with MDD and a HAM-D-25 score greater than or equal to20 were treated with open-label gepirone-IR 20 to 90 mg/day for 6 weeks. Responders with a HAM-D-17 total score less than or equal to12 or with a greater than or equal to50% reduction in total HAM-D-17 score and at least a much improved or very much improved CGI improvement score, were randomized to gepirone-IR or placebo for six additional weeks. Time to relapse was defined in six ways [(I) return to greater than or equal to75% of baseline HAM-D-17 total score; (2) CGI improvement score of no change or minimally worse, much worse or very much worse than baseline (greater than or equal to4); and four more definitions combining the HAM-D-17 or CGI criteria with discontinuation, or discontinuation due to lack of efficacy] and analyzed for the ITT population using the LOCF method. Of 134 patients in the open-label phase, 70 were responders. In the double-blind phase, the relapse rate was significantly lower with gepirone-IR than with placebo (Pless than or equal to0.05) for four of the six definitions of relapse. Discontinuations of gepirone-IR due to adverse events were observed for 26.9% of patients in the open-label phase, and four patients (6%) during the double-blind phase. The most frequent adverse events with gepirone-IR were dizziness, nausea, headache, and somnolence, and with placebo were headache and paresthesia. A relapse-prevention study of longer duration is needed to confirm these preliminary results. Gepirone-IR was significantly more effective than placebo for relapse prevention and demonstrated acceptable tolerability in outpatient responders with MDD. (C) 2003 Elsevier Ltd. All rights reserved.