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 efficacyand tolerability of venlafaxine and fluoxetine.

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

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

Conclusion: These results support the efficacyand tolerability of venlafaxine in comparison with fluoxetine fortreating outpatients with major depression.