Cusin, CristinaIovieno, NadiaIosifescu, Dan VNierenberg, Andrew AFava, MaurizioRush, A JohnPerlis, Roy H2022-04-142022-04-142013-070160-66891555-2101https://hdl.handle.net/10161/24821<h4>Background</h4>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.<h4>Method</h4>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.<h4>Results</h4>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 (χ(2) = 1.2, P = .27) and remission (χ(2) = 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.<h4>Conclusion</h4>For patients who have failed to respond to standard antidepressant therapies, pramipexole is a safe and potentially efficacious augmentation strategy.<h4>Trial registration</h4>ClinicalTrials.gov identifier: NCT00231959.HumansDopamine AgonistsAntidepressive AgentsDrug MonitoringTreatment OutcomeDrug Therapy, CombinationRemission InductionDouble-Blind MethodDepressive Disorder, MajorPsychiatric Status Rating ScalesDose-Response Relationship, DrugDrug SynergismDiagnostic and Statistical Manual of Mental DisordersAdultAgedMiddle AgedFemaleMaleBenzothiazolesDepressive Disorder, Treatment-ResistantPramipexoleJournal article2022-04-14