A DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF 2 DOSE RANGES OF NEFAZODONE IN THE TREATMENT OF DEPRESSED OUTPATIENTS

Background: Nefazodone hydrochloride, a 5-HT2 receptor antagonist that selectively inhibits serotonin reuptake, was evaluated in a double-bl ind, dose-finding study of novel design, involving 240 patients with m ajor depression. Method: Patients were randomly assigned to three trea tment groups and received either placebo (2-6 capsules per day), a low er-dose range of nefazodone (50-300 mg/day), or a higher-dose range of nefazodone (100-600 mg/day) for 6 weeks. Results: At the end of treat ment, the Hamilton Rating Scale for Depression and the clinician- and patient-rated Inventory for Depressive Symptomatology scores showed si gnificant improvement (p less than or equal to .05) for patients recei ving higher-dose range nefazodone (mean = 392 mg/day) compared with pl acebo treatment. The percentage of responders (at least ''much improve d'' on the Clinical Global Impressions-Improvement scale) in the highe r-dose range nefazodone group (58%) was significantly greater (p less than or equal to .05) than in the placebo group (39%). The treatment g roup receiving nefazodone in the lower-dose range was not differentiat ed in clinical response from placebo controls. The rate of discontinua tion for adverse experience (14%) was similar for patients treated wit h higher-dose range nefazodone and placebo. Conclusion: The findings o f this study indicate that nefazodone is an effective and well-tolerat ed antidepressant drug, with a recommended therapeutic dose range of 1 00 to 600 mg/day and a starting dose of 100 mg b.i.d.