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 ofa 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 OSM-IY) 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 (x²=1.2, P=.27) and remission (x²=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.