LONG-TERM SAFETY AND CLINICAL ACCEPTABILITY OF VENLAFAXINE AND IMIPRAMINE IN OUTPATIENTS WITH MAJOR DEPRESSION

The antidepressant efficacy and safety of venlafaxine was shown previo usly in 6-week, placebo-controlled trials. We evaluated the long-term safety and clinical acceptability of venlafaxine and imipramine in a d ouble-blind, parallel-group, comparative study. Two hundred ninety dep ressed outpatients were treated with venlafaxine, and an additional 91 received imipramine for as long as clinically necessary, up to 1 year . The total daily dose of each drug could vary from 75 to 225 mg. The Clinical Global Impressions Scale and a therapeutic response rate that was based on Clinical Global Impressions Scale-Improvement and incorp orated discontinuation information were used to evaluate efficacy. Saf ety determinations and patient subjective ratings were used to evaluat e safety and clinical acceptability. During the study, the adverse eve nts were generally mild to moderate and most subsided with continued t reatment; the most frequent were nausea for venlafaxine and dry mouth for imipramine. The anticholinergic side effect burden was significant ly higher in the imipramine group than in the venlafaxine group. Venla faxine was judged significantly more acceptable than imipramine, on th e basis of the subjective ratings by patients. Fewer venlafaxine-treat ed patients than imipramine-treated patients withdrew because of adver se events and unsatisfactory response. There was a consistent trend in the therapeutic response rates in favor of venlafaxine that reached s tatistical significance at months 2, 6, and 12. In this long-term stud y, patient acceptability was greater for venlafaxine than for imiprami ne, suggesting therapeutic advantages for venlafaxine in the long-term treatment of depression. Additional studies with other active compara tors are underway to confirm and extend these encouraging results.