The heterogeneity of depression suggests that different neurocircuits and pathophysiological
mechanisms are involved. Anhedonia - the inability to experience pleasure from, or the lack
of motivation to carry out, usually enjoyable activities - is an endophenotype within the
depression spectrum, with a distinct pathophysiology of dopaminergic mesolimbic projections.
Anhedonia is common in depression and associated with treatment resistance. Pramipexole, an
agonist to the dopamine -receptor 3, is an established treatment of Parkinson's disease.
Based on its mechanism of action, pramipexole might be efficacious in a subtype of depression
characterized by anhedonia and lack of motivation - symptoms linked to dopaminergic
hypofunction. In this proof-of-concept pilot study the investigators test the anti-anhedonic
and antidepressant effects of add-on pramipexole using an "enriched population study design"
including only depressed patients with significant anhedonia. To understand the neurobiology
of anhedonia in depression and to identify treatment predictors, the investigators also do
assessments of anhedonia-related neurocircuitry using (f)MRI and blood biomarkers.