A Randomized, Double-Blind, Placebo-Controlled Trial of Pramipexole Augmentation in Treatment-Resistant Major Depressive Disorder

Background: Multiple treatments for patients with major depressive disorder (MDD) have demonstrated efficacy, but up to one-third of individuals with MDD do not achieve symptomatic remission despite various interventions. Existing augmentation or combination strategies can have substantial safety concerns that may limit their application.

Method: This study investigated the antidepressant efficacy of a flexible dose of the dopamine agonist pramipexole as an adjunct to standard antidepressant treatment in an 8-week, randomized, double-blind, placebo-controlled trial conducted in a tertiary-level depression center. We randomized 60 outpatients (aged 18 to 75 years) with treatment-resistant nonpsychotic MDD (diagnosed according to DSM-IV) to either pramipexole (n = 30) or placebo (n = 30). Treatment resistance was defined as continued depression (Montgomery-Asberg Depression Rating Scale [MADRS] score ≥ 18) despite treatment with at least 1 prior antidepressant in the current depressive episode. Patients were recruited between September 2005 and April 2008. The primary outcome measure was the MADRS score.

Results: The analyses that used a mixed-effects linear regression model indicated a modest but statistically significant benefit for pramipexole (P = .038). The last-observation-carried-forward analyses indicated that 40% and 33% of patients randomized to augmentation with pramipexole achieved response (χ2 = 1.2, P = .27) and remission (χ2 = 0.74, P = .61), respectively, compared to 27% and 23% with placebo; however, those differences were not statistically significant. Augmentation with pramipexole was well-tolerated, with no serious adverse effects identified.

Conclusion: For patients who have failed to respond to standard antidepressant therapies, pramipexole is a safe and potentially efficacious augmentation strategy.

Trial Registration: ClinicalTrials.gov identifier: NCT00231959

J Clin Psychiatry 2013;74(7):e636-e641

© Copyright 2013 Physicians Postgraduate Press, Inc.

Submitted: August 13, 2012; accepted December 17, 2012 (doi:10.4088/JCP.12m08093).

Corresponding author: Cristina Cusin, MD, Depression Clinical and Research Program, Massachusetts General Hospital, One Bowdoin Square, Ste 630, Boston, MA 02114 ([email protected]).