Efficacy and Tolerability of Once-Daily Venlafaxine Extended Release (XR) in Outpatients With Major Depression

Background: This was a randomized, double-blind, placebo-controlled evaluation of the efficacy and safety of once-daily venlafaxine extended release (XR) in outpatients with DSM-IV major depression.

Method: Patients were randomly assigned to venlafaxine XR (75_225 mg) once daily or placebo for up to 8 weeks. The primary efficacy variables were the 21-item Hamilton Rating Scale for Depression (HAMD) total score and HAM-D depressed mood item, the Montgomery-Asberg Depression Rating Scale (MADRS) total scores, and the Clinical Global Impressions (CGI) Severity scale. Data were analyzed on a modified intent-to-treat basis using the last-observation- carried-forward method.

Results: Venlafaxine XR (N=91) was significantly more effective than placebo (N=100) beginning at Week 2 on the CGI Severity scale, at Week 3 on the HAM-D depressed mood item, and at Week 4 on the HAM-D and MADRS; this superiority was maintained through Week 8. The most common treatment-emergent adverse events associated with venlafaxine XR were nausea, insomnia, and somnolence. The incidence of nausea was highest during the first week, decreased by 50% during the second week, and was comparable to that of placebo from Week 3 onward.

Conclusion: These results demonstrate that venlafaxine XR is an effective and well-tolerated treatment of major depression.