The use of venlafaxine in the treatment of major depression and major depression associated with anxiety: a dose-response study. Venlafaxine Investigator Study Group

This 12-week, double-blind, placebo-controlled study evaluated the efficacy and safety of venlafaxine as first-line therapy for the treatment of major depression and major depression associated with anxiety in 384 adult outpatients. Fixed total daily dosages of 75, 150, and 200 mg of venlafaxine were administered in a twice-a-day regimen. Primary efficacy parameters were the Hamilton Rating Scale for Depression (HAM-D) total score, the HAM-D Depressed Mood Item, the Montgomery-Asberg Depression Rating Scale total score, and the Clinical Global Impressions Scale. Overall, a higher percentage of patients responded to venlafaxine than to placebo. Efficacy data indicated a dose-related response, most evident in the onset of clinical improvement; statistically significant improvements in some primary parameters were seen as early as 1 to 2 weeks after initiation of treatment, especially in the 150-and 200-mg/day groups. These dose-related clinical improvements continued through week 12. Venlafaxine-treated patients who had depression associated with anxiety showed significant dose-related improvements compared with placebo-treated patients; improvement was noted by scores on the HAM-D Anxiety-Psychic Item and Anxiety-Somatization Factor. Few clinically significant changes were observed in laboratory values, vital signs, or electrocardiogram tracings. Venlafaxine was generally well tolerated at all dosages. The most common study events included nausea, dizziness, somnolence, insomnia, dry mouth, and asthenia, which are consistent with findings of previous studies. The current study demonstrated that 75 to 200 mg/day of venlafaxine twice daily produced a dose-related improvement in the primary efficacy parameters and in the onset of significant antidepressant effects, which was noted at weeks 1 to 2 with the highest dosage tested (200 mg/day). The study also demonstrated that these dosages of venlafaxine were safe and effective as first-line therapy for major depression and depression associated with anxiety.