Comparison of Venlafaxine and Imipramine in the Acute Treatment of Major Depression in Outpatients

Background: Venlafaxine is a new phenylethylamine antidepressant that exhibits monoamine reuptake inhibition. The current study evaluates the efficacy of venlafaxine compared to that of imipramine in outpatients suffering from major depression of moderate-to-marked severity.

Method: We conducted a double-blind, placebo-controlled, 6-week treatment study of 224 outpatients who met DSM-III-R criteria for major depression, and who had a score of at least 20 on the 21-item Hamilton Rating Scale for Depression (HAM-D). Dosage was flexible and administered on a three-times-a-day schedule, with a mean maximum daily dose of 182 mg for venlafaxine and 176 mg for imipramine.

Results: For patients completing 6 weeks of treatment with venlafaxine, the HAM-D total score improved by 16.6 +/- 4.9 points. Improvement at 6 weeks was 13.6 +/- 6.3 points for patients treated with imipramine and 10.6 +/- 7.8 points for patients treated with placebo (p < .05 for active drug vs. placebo). Ninety percent of venlafaxine completers were rated as "much" or "very much" improved on the Clinical Global Impression-Improvement scale, compared to 79% treated with imipramine and 53% treated with placebo (p < .05). An endpoint analysis, where the last scores of patients who dropped out were carried forward to subsequent visits, showed significant efficacy only for venlafaxine and not imipramine, probably because of the higher attrition for the latter drug. Overall, both venlafaxine and imipramine were well-tolerated, with venlafaxine having a somewhat lower attrition rate due to adverse effects than imipramine (16% vs. 25%).

Conclusion: These results, together with those of previously reported studies, suggest that venlafaxine has antidepressant efficacy comparable to that provided by available antidepressants.