Nefazodone: aspects of efficacy

Abstract

Background: Nefazodone hydrochloride, a 5-HT2 receptor antagonist and serotonin (5-HT) uptake inhibitor, was evaluated in four Phase 3 double-blind, imipramine- and placebo-controlled studies involving outpatients with major depression.

Method: Patients who qualified for well-controlled efficacy trials in major depression were enrolled in a series of active- and placebo-controlled trials to establish the comparative efficacy of nefazodone and a standard tricyclic antidepressant drug. The primary efficacy measures employed were the 17-item Hamilton Rating Scale for Depression (HAM-D-17) and the Clinical Global Improvement (CGI) scale. Safety profiles were also compared as well as survival analyses of double-blind acute and continuation treatment of patients in efficacy trials.

Results: Three of four Phase 3 active- and placebo-controlled studies showed nefazodone to be an effective antidepressant drug with overall efficacy generally similar to that of imipramine. The remaining study did not differentiate either active drug from placebo controls. Superiority of nefazodone and imipramine over placebo was evidenced by greater improvement on core depression symptoms in addition to the primary outcome measures (HAM-D-17 and CGI). The incidence of side effects and premature treatment discontinuations for imipramine-treated patients was higher than for nefazodone therapy. Both drugs showed evidence of continuing efficacy during long-term treatment with significantly fewer dropouts (p < .05) than for placebo controls.

Conclusion: Nefazodone, an antidepressant that modulates serotonin receptors and enhances serotonin-mediated neurotransmission, has been shown to be an effective and well-tolerated new antidepressant drug with greater patient acceptability and safety than imipramine.