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 (MDD) in comparison to imipramine and placebo treatments. It also compares two dose ranges of nefazodone to investigate its optimal dose range.

METHOD

Nefazodone was evaluated in a 6-week, double-blind trial of novel design involving 180 patients meeting Research Diagnostic Criteria for major depressive disorder and having a minimum pretreatment score of 22 on the first 17 items of the Hamilton Rating Scale for Depression (HAM-D). Patients were randomly assigned to placebo (2-10 capsules/day), imipramine (50-250 mg/day), or nefazodone in two dose ranges (50-250 mg/day or 100-500 mg/day).

RESULTS

Improvement on depression measures with nefazodone in the 100-500-mg/day dose range (endpoint mean = 460 mg/day) and imipramine (endpoint mean = 214 mg/day) exceeded that with placebo. Some benefit was also observed in the nefazodone 50-250-mg/day treatment group (endpoint mean = 242 mg/day), but it was suboptimal. Evidence of nefazodone's efficacy as an antidepressant was consistently observed on physician- (HAM-D, Clinical Global Impressions [CGI]) and patient-rated (CGI-patient rated) scales. By patient self-report, improvement of anxiety symptoms associated with depression was evident with nefazodone as early as the first week of treatment, and benefit was seen with both nefazodone dosage groups. Analyses of the physician's global assessments of therapeutic effect and side effects at end of treatment showed therapeutic benefit for both nefazodone and imipramine treatments; however, patients in the nefazodone treatment groups were significantly less troubled by adverse experiences than were imipramine-treated patients, resulting in a lower dropout rate for adverse experience.

CONCLUSION

Nefazodone is a well-tolerated and effective antidepressant for the treatment of major depressive disorder.