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 > or = 20 were treated with open-label gepirone-IR 20 to 90 mg/day for 6 weeks. Responders with a HAM-D(17) total score < or = 12 or with a > or = 50% 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 [(1) return to > or = 75% 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 (> or = 4); 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 (P < or = 0.05) 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.
Depression Research Unit, Department of Psychiatry, University of Pennsylvania School of Medicine, University Science Center, 3535 Market Street, 3rd Floor, Philadelphia, PA 19104, USA. jamsterd@mail.med.upenn.edu
Jay D
JD
Amsterdam
David J
DJ
Brunswick
Michael
M
Gibertini
D000284:Administration, Oral; D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000928:Antidepressive Agents; D010919:Placebos; D011743:Pyrimidines; C039979:gepirone