A DOUBLE-BLIND COMPARISON OF NEFAZODONE, IMIPRAMINE, AND PLACEBO IN MAJOR DEPRESSION

Background. Nefazodone is a 5-HT2-receptor antagonist and serotonin (5 -HT) selective reuptake inhibitor. This study evaluates the safety and efficacy of nefazodone in patients with major depressive disorder (MD D) in comparison to imipramine and placebo treatments. It also compare s two dose ranges of nefazodone to investigate its optimal dose range. Method. Nefazodone was evaluated in a 6-week, double-blind trial of n ovel design involving 180 patients meeting Research Diagnostic Criteri a for major depressive disorder and having a minimum pretreatment scor e of 22 on the first 17 items of the Hamilton Rating Scale for Depress ion (HAM-D). Patients were randomly assigned to placebo (2-10 capsules /day), imipramine (50-250 mg/day), or nefazodone in two dose ranges (5 0-250 mg/day or 100-500 mg/day). Results: Improvement on depression me asures with nefazodone in the 100-500-mg/day dose range (endpoint mean = 460 mg/day) and imipramine (endpoint mean = 214 mg/day) exceeded th at with placebo. Some benefit was also observed in the nefazodone 50-2 50-mg/day treatment group (endpoint mean = 242 mg/day), but it was sub optimal. Evidence of nefazodone's efficacy as an antidepressant was co nsistently observed on physician- (HAM-D, Clinical Global Impressions [CGI]) and patient-rated (CGI-patient rated) scales. By patient self-r eport, improvement of anxiety symptoms associated with depression was evident with nefazodone as early as the first week of treatment, and b enefit was seen with both nefazodone dosage groups. Analyses of the ph ysician's global assessments of therapeutic effect and side effects at end of treatment showed therapeutic benefit for both nefazodone and i mipramine treatments; however, patients in the nefazodone treatment gr oups were significantly less troubled by adverse experiences than were imipramine-treated patients, resulting in a lower dropout rate for ad verse experience. Conclusion: Nefazodone is a well-tolerated and effec tive antidepressant for the treatment of major depressive disorder.