Effectiveness of Pramipexole for Treatment-Resistant Depression

Inclusion Criteria: * Meets diagnostic criteria for major depressive disorder * Meets criteria for current major depressive episode * Score of at least 18 on the Montgomery-Asberg Depression Rating Scale (MADRS) at the baseline visit * Currently being treated with antidepressant monotherapy at an adequate dose for 6 weeks or willing to enter open lead-in treatment * Agrees to use an effective form of contraception throughout the study Exclusion Criteria: * Pregnant * At risk for suicide or homicide * Unstable medical illness (e.g., cardiovascular, liver, kidney, respiratory, endocrine, or neurologic disease, including uncontrolled seizure disorder) * History of a substance use disorder within 6 months of study enrollment * History of or current psychotic features * Currently being treated with typical or atypical antipsychotic medications * Currently being treated with a medication known to significantly decrease pramipexole clearance (e.g., cimetidine, ranitidine, diltazem, verapamil, quinine or triamterene) * Clinical or laboratory evidence of untreated hypothyroidism * History of a 2-week or longer course of pramipexole * Intolerance of pramipexole at any dose * Any investigational psychotropic drug use within the last three months * Level 3 or greater antidepressant resistance as assessed by the ATHF * Three or more episodes of self-harm in the year prior to study enrollment * Documented history of poor treatment adherence or frequently missed appointments * Parkinson's disease