Pramipexole, a Dopamine Agonist, in Major Depression: Antidepressant Effects and Tolerability in an Open-Label Study with Multiple Doses

Summary: The safety, tolerability, and the antidepressant effects of pramipexole, a dopaminergic agonist, were assessed in 26 patients hospitalized for major depression. Total daily doses ranged from 1.75 to 9.0 mg using a 14-day dose escalation phase to reach the target or highest attainable dose, which was then administered unchanged for an additional 14 days. The study was terminated at the 6.25-mg dose level because nausea, restlessness, headache, and insomnia became dose-limiting. No clinically important laboratory, electrocardiographic, or vital sign abnormalities were noted. Ninety-six percent of the patients (25/26) were markedly or severely ill by the Clinical Global Impression severity scale at the start of the study, whereas only 27% (7/26) remained in this category at the final visit. Pramipexole administration resulted in consistent reductions in clinical depression. Scores on three major rating scales showed reductions of ≥35% in 13, 12, and 10 of the 26 patients, respectively. A more marked improvement of at least 50% was also noted in a substantial number of patients (MADRS 9/26, BRMES 7/26, and HAMD-17 6/26). This escalating dose-tolerance study with preliminary efficacy data demonstrated sufficient safety and antidepressant properties of pramipexole in severely depressed patients to justify a larger doubleblind, placebo-controlled trial.