Randomized, Double-Blind Comparison of Venlafaxine and Fluoxetine in Outpatients With Major Depression

Background: This was an 8-week, multicenter, randomized, double-blind, parallel-group study of the efficacy and tolerability of venlafaxine and fluoxetine.

Method: Outpatients with DSM-III-R major depression, a minimum score of 20 on the 21item Hamilton Rating Scale for Depression (HAM-D), and depressive symptoms for at least 1 month were eligible. Patients were randomly assigned to treatment with venlafaxine, 37.5 mg twice daily, or fluoxetine, 20 mg once daily. The dose could be increased to venlafaxine, 75 mg twice daily, or fluoxetine, 20 mg twice daily, after 3 weeks for a poor response. The primary efficacy variables were the final on-therapy scores on the HAM-D, Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impressions Severity of Illness (CGI-S) and Improvement (CGII) scales.

Results: Three hundred eighty-two patients were randomly assigned to therapy and included in the intent-to-treat analysis. Both venlafaxine and fluoxetine produced significant reductions from baseline to day 56 in mean HAM-D, MADRS, and CGI-S scores, but no significant differences were noted between groups. Among patients who increased their dose at 3 weeks, significantly (p < .05) more patients taking venlafaxine than taking fluoxetine had a CGI-I score of 1 (very much improved) at the final evaluation. The most frequent adverse events were nausea, headache, and dizziness with venlafaxine and nausea, headache, and insomnia with fluoxetine.

Conclusion: These results support the efficacy and tolerability of venlafaxine in comparison with fluoxetine for treating outpatients with major depression.

J Clin Psychiatry 1998;59(7):352-357