Once-daily venlafaxine extended release (XR) and venlafaxine immediate release (IR) in outpatients with major depression. Venlafaxine XR 208 Study Group.
This was a randomized, double-blind, placebo-controlled comparison of the efficacy and safety of once-daily venlafaxine extended release (XR) and venlafaxine immediate release (IR). Outpatients with DSM-III-R major depression were randomly assigned to venlafaxine XR, 75 mg once daily, venlafaxine IR, 37.5 mg twice daily, or placebo for a maximum of 12 weeks. If the response was inadequate after 2 weeks of treatment, the dosage of venlafaxine XR or IR could be increased to 150 mg daily. The primary efficacy variables were the 21-item Hamilton Depression (HAM-D) Rating Scale total score and depressed mood item, the Montgomery-Asberg Rating Scale (MADRS) total scores, and the Clinical Global Impressions (CGI) severity scale. Two hundred seventy-eight patients were evaluated for efficacy. Venlafaxine XR was significantly superior (p < 0.05) to placebo beginning at week 2 for the HAM-D, week 3 for the MADRS, and week 4 for the CGI severity. Similarly, venlafaxine IR was significantly superior (p < 0.05) to placebo beginning at week 2 on the HAM-D total and depressed mood item, week 3 on the MADRS total, and week 6 on the CGI severity scales. Venlafaxine XR exhibited superiority (p < 0.05) over venlafaxine IR at week 12 for all efficacy variables. The most common treatment-emergent adverse event with venlafaxine XR was nausea. The incidence of nausea was highest during the first 2 weeks with a low likelihood of developing nausea thereafter. The results of this study indicate that venlafaxine XR is safe, effective, and well tolerated for the treatment of major depression at once-daily doses ranging from 75 to 150 mg.