A randomized, double-blind comparison of a rapidly escalating dose of venlafaxine and imipramine in inpatients with major depression and melancholia

Abstract

A double-blind, randomized, parallel study in 167 hospitalized patients with major depression and melancholia was conducted to determine if rapidly escalated doses of venlafaxine produced an earlier response, compared with rapidly escalated doses of imipramine. The daily dose of venlafaxine was rapidly increased to 375 mg/day over a five-day period, was maintained at this level for 10 days, and then was reduced to 150 mg/day for the remainder of the study. The imipramine dose was rapidly increased to 200 mg/day over five days and was maintained at this level to the end of the study. The primary efficacy variables were time to response and time to sustained response on the HAM-D and MADRS. No differences in the response rates on the HAM-D or MADRS were observed between treatments. However, among patients who demonstrated a response on the HAM-D, there was a significantly faster onset of response (p = 0.036) and sustained response (p = 0.018) in the venlafaxine group. The median time to response on the HAM-D among responders was 14 days with venlafaxine and 21 days with imipramine. However, no differences between treatments were observed among responders on the MADRS (median time to response: 15 days for venlafaxine, 18 days for imipramine). Study events were reported in 69% of venlafaxine-treated patients and 76% of imipramine-treated patients. In severely depressed patients with melancholia, a faster onset of response was observed with venlafaxine on the HAM-D, but not the MADRS, and maximal tolerated doses of venlafaxine and imipramine were comparable for overall efficacy. These results confirm and extend previous observations and suggest that venlafaxine may have an early onset of action and may produce a rapid response in hospitalized patients with severe depression complicated by melancholia.