NEFAZODONE - ASPECTS OF EFFICACY

Background: Nefazodone hydrochloride, a 5-HT2 receptor antagonist and serotonin (5-HT) uptake inhibitor, was evaluated in four Phase 3 doubl e-blind, imipramine- and placebo-controlled studies involving outpatie nts with major depression. Method: Patients who qualified for well-con trolled 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. T he 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 ana lyses of double-blind acute and continuation treatment of patients in efficacy trials. Results: Three of four Phase 3 active- and placebo-co ntrolled studies showed nefazodone to be an effective antidepressant d rug 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 e videnced by greater improvement on core depression symptoms in additio n 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 sh owed evidence of continuing efficacy during long-term treatment with s ignificantly fewer dropouts (p < .05) than for placebo controls. Concl usion: Nefazodone, an antidepressant that modulates serotonin receptor s and enhances serotonin-mediated neurotransmission, has been shown to be an effective and well-tolerated new antidepressant drug with great er patient acceptability and safety than imipramine.