A Small Placebo-Controlled Trial Links Pramipexole to Reduced Anhedonia in Mood Disorders

A single-center RCT (n=85) finds the Parkinson's drug pramipexole, added to existing treatment, was associated with significantly lower anhedonia scores — but researchers caution the findings are preliminary.

Anhedonia — the diminished ability to feel pleasure — is one of the most disabling and treatment-resistant features of mood disorders, and existing antidepressants often leave it largely unaddressed. A small randomized trial published in Nature Medicine now offers one of the first controlled signals that a dopamine-targeting drug may help.

Researchers at Skane University Hospital in Lund, Sweden enrolled 85 adults with major depressive disorder, dysthymia, or bipolar depression who had clinically elevated scores on the Snaith-Hamilton Pleasure Scale (SHAPS), a validated measure of anhedonia. In the single-center, double-blind, placebo-controlled trial, participants were randomly assigned to add flexible-dose oral pramipexole — a D2/D3 dopamine receptor agonist approved for Parkinson’s disease and restless legs syndrome — or placebo on top of their existing treatments for 9 weeks.

The trial met its primary endpoint. Adults with mood disorders who received pramipexole showed a significantly greater reduction in SHAPS scores compared with placebo (mean difference: -4.04; 95% CI: -6.89 to -1.18; p = 0.006; Hedges’ g = 0.62), an effect size in the moderate range. Exploratory neuroimaging analyses found that pramipexole was associated with relative preservation of reward-related ventral striatal activation on fMRI — biological evidence suggesting the drug engaged its intended dopaminergic target. A separate 6-month open-label extension found improvements sustained, though without a placebo comparator this phase cannot establish whether benefit persisted due to the drug alone.

Important limitations: This is a single-center RCT with 82 participants in the primary analysis, making it a preliminary finding that requires replication in larger, multicenter trials. The study population was specifically adults with mood disorders and elevated anhedonia — results cannot be generalized beyond that group. The trial tested pramipexole as an add-on strategy, not as a replacement for standard antidepressant therapy, and pramipexole is not approved for depression or anhedonia. No head-to-head comparison with standard antidepressants was conducted.

This article reports preliminary research findings and does not constitute medical advice. Patients should not change medications without consulting a physician.

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