Venlafaxine for Treatment-Resistant Unipolar Depression

TLDR

The study evaluated venlafaxine as a treatment for patients with treatment‑resistant unipolar depression. Eighty‑four patients meeting DSM‑III‑R criteria for major depression who had failed at least three adequate antidepressant trials, two classes or ECT, and one augmentation attempt received open‑label venlafaxine and were assessed at baseline and regular intervals using the HAM‑D‑21, MADRS, and CGI scales with predefined response thresholds. After 12 weeks, roughly one‑third of patients achieved full or partial response (32.9% HAM‑D‑21, 30% MADRS, 40% CGI), and nearly half of responders maintained improvement for at least three months, indicating venlafaxine benefits a small but significant minority of rigorously defined triple‑resistant patients.

Abstract

The purpose of this study is to evaluate the novel antidepressant venlafaxine for the management of treatment-resistant unipolar depression. We gave unblinded venlafaxine to 84 consecutive outpatients and inpatients who met DSM-III-R criteria for major depression and who had failed to respond to at least three adequate trials of antidepressants from at least two different antidepressant classes or electroconvulsive therapy, plus at least one attempt at augmentation. Patients were evaluated after a drug free period at baseline and regular intervals with the 21-item Hamilton Rating Scale for Depression (HAM-D-21), Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impressions Scale Improvement item (CGI). Full response for each scale was defined as follows: HAM-D-21 score of 8 or lower, a MADRS score of 12 or lower, and CGI score of 1; partial responses was defined as a 50% decrease in the HAM-D and MADRS, with final scores greater than 8 and 12, respectively, and for the CGI, a score equal to 2. About a third of patients were considered to be either full or partial responded (32.9% by HAM-D-21, 30.0% by MADRS, and 40% by CGI) after 12 weeks of venlafaxine treatment. To date, about 46% of responders have sustained their response for at least 3 months after the acute response. Venlafaxine is effective for a significant, but small, minority of patients with rigorously defined triple-resistant depression; the improvement was maintained for about half of the responders for the first 3 months of maintenance therapy.