An eight-week, open-label, uncontrolled, multicenter, phase IV study of remission rates in outpatients and inpatients with major depression treated with venlafaxine

Background: Venlafaxine is a structurally novel antidepressant that is believed to potentiate monoamine activity in the central nervous system. In preclinical studies, venlafaxine was shown to inhibit the neuronal uptake of serotonin and norepinephrine and, to a lesser degree, dopamine reuptake, but was without effect on monoamine oxidase (MAO) activity. Clinical trial results from similar to3000 patients suggest that venlafaxine is a safe and effective antidepressant with the potential to invoke an early onset of clinical activity. Objective: The purpose of this 8-week, open-label, uncontrolled, multi-center, Phase IV study was to examine the extent of remission and symptom relief in outpatients and inpatients with major depressive disorder treated with venlafaxine. Methods: This study was conducted at 12 centers across Belgium and Luxembourg. Consecutive, severely depressed inpatients and moderately depressed outpatients aged 18 to 70 years were eligible. Patients were administered open-label venlafaxine for 8 weeks. Dosing was initiated at venlafaxine 75 mg/d (37.5 mg BID), with dose adjustments made throughout the study, to a maximum daily dose of 375 mg for inpatients and 225 mg for outpatients. Results were measured using the Hamilton Depression (HAM-D) scale, the Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impression (CGI) scale. Results: A total of 149 consecutive patients (84 females, 65 males; mean age, 46.5 years; 88 outpatients, 61 inpatients) were enrolled; the intent-to-treat (ITT) population comprised 144 patients (84 outpatients, 60 inpatients); 111 patients (64 outpatients, 47 inpatients) completed the study. At the week 8 visit, 71.3% of patients (77/108) were considered to be responders according to the HAM-D scale; 73.8% (79/107) according to the MADRS; and 78.7% (85/108) according to the CGI scale. A sustained response was achieved in 33.3% of the ITT population (48/144), and at week 8, 50.8% of outpatients (32/63) and 37.8% of inpatients (17/45) were in remission according to the HAM-D scale. Venlafaxine was well tolerated at all doses, with the most frequently experienced adverse events (AEs) being nausea, sweating, and headache. Fewer inpatients than outpatients reported greater than or equal to 1 AE (57.4% [35/61] and 73.9% [65/88], respectively), despite receiving a higher maximum daily dose of venlafaxine. Conclusion: The results of this study indicate that venlafaxine was a tolerable and effective antidepressant in both outpatients and inpatients, with a significant proportion of patients achieving remission.