Double-blind, placebo-substitution study of nefazodone in the prevention of relapse during continuation treatment of outpatients with major depression.

The efficacy of nefazodone in prevention of relapse of depression was evaluated in a 36-week double-blind, placebo-substitution, continuation treatment trial. After 16 weeks of acute, single-blind treatment with nefazodone, 131 patients responding to treatment and in stable remission were randomized in a 36-week double-blind trial to either nefazodone (n = 65) or placebo (n = 66). Patients were defined as having relapsed if they had a total score > or = 18 on the 17-item Hamilton Depression Scale on two consecutive visits or if they discontinued treatment for lack of efficacy. Relapse rates were significantly lower for patients randomized to continued nefazodone treatment than for patients switched to placebo. Kaplan-Meier estimates of relapse rates 9 months (36 weeks) after the end of acute treatment were 1.8% for nefazodone versus 18.3% for placebo (P = 0.009) by the Hamilton Depression Scale and 17.3% versus 32.8% (P = 0.028) by discontinuation for lack of efficacy. The mean modal dose of nefazodone was 412 mg/day at study endpoint. These results demonstrate the clinical effectiveness of up to 1 year's treatment (16 weeks acute and 36 weeks continuation) with nefazodone in depressed patients. Long-term efficacy of nefazodone was accompanied by a good safety profile without any weight gain and with minimal symptoms of withdrawal upon abrupt discontinuation of treatment.

A double-blind, randomized, placebo-controlled trial of once-daily venlafaxine extended release (XR) and fluoxetine for the treatment of depression.

BACKGROUND: We compared the efficacy and tolerability of venlafaxine XR with that of fluoxetine in a multicenter, randomized, double-blind, placebo-controlled study in depressed outpatients. METHODS: Outpatients, 18 years and older, who met DSM-IV criteria for major depressive disorder were included (n = 301 randomized; 232 completed). Patients were randomly assigned to eight weeks of treatment with either venlafaxine XR 75-225 mg/day (n = 100), fluoxetine 20-60 mg/day (n = 103), or placebo (n = 98). The primary efficacy outcome measures were the final ratings on the Hamilton Rating Scale for Depression (HAM-D21) total score, HAM-D21 depressed mood item, Montgomery-Asberg Depression Rating Scale total score, and Clinical Global Impressions Scale. RESULTS: Withdrawal from the study due to adverse events occurred in 6% of the patients in the venlafaxine XR group and 9% of the patients in the fluoxetine group. Patients treated with venlafaxine XR, but only rarely those treated with fluoxetine, had statistically significant improvements in their depression ratings compared with placebo at the end of the study. The percentages of patients who achieved full remission of their depression (HAM-D21 total score < or = 7) at the end of treatment were 37%, 22% and 18% for the venlafaxine XR, fluoxetine and placebo groups, respectively. The differences in remission rates between venlafaxine XR and the other groups were statistically significant (p < 0.05). LIMITATIONS: The superior remission outcome observed with venlafaxine XR treatment needs to be replicated in additional studies. CONCLUSION: Venlafaxine XR is a well-tolerated and efficacious treatment for depression. The results of this study suggest that venlafaxine XR is as well-tolerated as fluoxetine but may have some efficacy advantages over fluoxetine.

A double-blind comparison of gepirone extended release, imipramine, and placebo in the treatment of outpatient major depression.

We report the results from one site of a two-site, double-blind, placebo-controlled comparison study of gepirone extended release (ER) and imipramine in the management of major depression. In the study, 123 subjects with DSM-III-R major depression were randomized to 8 weeks of treatment with gepirone ER (10-60 mg/day), imipramine (50-300 mg/day), or placebo. According to last observation carried forward (LOCF) analyses of 120 intent-to-treat subjects, both gepirone ER and imipramine were superior to placebo at Weeks 6 and 8 on the Hamilton Rating Scale for Depression 17- and 28-item (HAM-D-17 and HAM-D-28) instruments, the Clinical Global Impressions (CGI) Severity of illness scale, and the total Bech Six-Item Core Depression Cluster score. Gepirone ER was better tolerated than imipramine when judged by dropout rates for adverse events.