REVIEW OF: Browning M et al, Lancet Psychiatry 2025;12:579–589; Mishra BR et al, J Affect Disord 2025;390:119891
STUDY TYPE: RCTs

Two recent RCTs evaluated pramipexole, a dopamine agonist used for Parkinson’s disease, in treatment-resistant depression (TRD).

In the UK PAX-D trial (Browning et al), 151 patients with difficult-to-treat depression took pramipexole (up to 2.5 mg/day) or placebo for nearly a year, in addition to antidepressants. At 12 weeks, symptom scores, response, and remission rates all favored pramipexole, and gains held at 48 weeks. Side effects led to 20% discontinuation, mostly from nausea or dizziness. Some patients reported mild, reversible impulse-control issues, and there were rare cases of psychosis and hypomania.

In an Indian open-label RCT (Mishra et al), 150 patients with TRD received sertraline plus an add-on—low-dose pramipexole (0.375 mg/day), 200 mg/day of amantadine, or 100 mg/day of quetiapine—for 8 weeks. All groups improved, but pramipexole produced greater reductions in depression scores (HAM-D, CGI) and achieved higher response (36%) and remission (50%) rates. Side effects were mild and similar across groups, with no psychosis or impulse-control problems.

CARLAT TAKE
These studies suggest pramipexole has genuine antidepressant effects. Although it was open-label, the low-dose augmentation strategy reported solid efficacy with fewer side effects. While not yet mainstream, pramipexole deserves a place on your radar for TRD—just start low and monitor closely for dopaminergic side effects.