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Recent studies have shown venlafaxine to be an effective first-line agent for patients who have depression of varying severity. Two representative clinical trials to assess the efficacy of venlafaxine were reviewed: one in severely ill hospitalized patients and the other in outpatients. Efficacy was assessed using scores on several rating scales for 93 inpatients in the placebo-controlled trial and 224 outpatients in the active-control trial. Demographics and baseline scores were similar among study patients in each trial. In both trials, venlafaxine was significantly more effective than placebo. The study of inpatients demonstrated a rapid onset of antidepressant efficacy of venlafaxine and a reduction in comorbid symptoms of anxiety. In the study of outpatients, anticholinergic side effects commonly associated with tricyclic antidepressants such as imipramine were not found to be associated with venlafaxine, although some nausea occurred. Results of these clinical studies confirm those of previous studies that have shown venlafaxine to be an effective first-line agent for the management of depression in both hospitalized patients and outpatients.