Pramipexole Add-On Reduces Anhedonia in Treatment-Resistant Depression: Lund RCT with 7T fMRI Target Engagement

The Lund University study enrolled adults with documented anhedonia who had failed at least two adequate antidepressant trials. Participants received pramipexole or placebo added to stable medication; primary outcomes included anhedonia scales, actigraphy-derived activity, and 7T fMRI BOLD response in the ventral striatum during reward tasks. The pramipexole arm demonstrated larger reductions in anhedonia scores, increased daily movement, and enhanced striatal activation, consistent with dopamine D3 receptor agonism restoring reward processing.

This repurposing approach builds on earlier open-label and small controlled studies of pramipexole in major depression that reported modest overall response rates but rarely isolated anhedonia or included imaging. The current design strengthens causal inference by linking clinical change to a predefined neural target, yet the modest sample size and single-site recruitment limit generalizability; common side effects of nausea and sleep disturbance were manageable with titration, though impulse-control risks require ongoing monitoring.

Larger multicenter trials with longer follow-up and active comparators are required to establish whether benefits persist beyond six months and whether pramipexole outperforms or augments existing augmentation strategies such as aripiprazole or ketamine. Regulatory interest in dopamine agonists for motivational symptoms may accelerate if these findings replicate.