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.
Amsterdam
Jay D
JD
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
Brunswick
David J
DJ
Gibertini
Michael
M
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