The heterogeneity of depression suggests that several 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 a promising
endophenotype within the depression spectrum, with a distinct pathophysiology involving
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. This is supported by animal data, clinical
experience, and recent pilot study data, but RCTs are lacking. In this double-blind
placebo-controlled RCT the anti-anhedonic and antidepressant effects of add-on pramipexole
will be tested, using an "enriched population study design" including only depressed patients
with significant anhedonia. To better understand the neurobiology of anhedonia in depression
and to identify treatment predictors, simultaneous assessments of anhedonia-related
neurocircuitry using (f)MRI will be done, and anhedonia-related biomarkers in blood and
cerebrospinal fluid analyzed. The aim of the study is to confirm the efficacy of pramipexole
in this depression subtype, which would be an important step towards personalized medicine in
psychiatry.