Pramipexole for Anhedonic Depression

• Status: Not yet recruiting
• Trial end date: 2027-03-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Region Skane
• Collaborator: Lund University
• Treatments: Pramipexole

Criteria

Inclusion Criteria:

• Age between 18 years and 75 years.

• Informed consent

• Diagnosis of unipolar depressive episode, bipolar disorder in depressive phase, exhaustion disorder or dysthymia.

• All patients should have clinically significant anhedonia symptoms (SHAPS score 3 or 4 on ≥ 3 items).

• Subjects must have an ongoing stable treatment with at least one antidepressant / mood stabilizer for at least 4 weeks.

Exclusion Criteria:

• Ongoing pregnancy, breastfeeding or planned pregnancy.

• High risk of suicide.

• Substance abuse.

• Psychosis.

• Borderline personality disorder.

• Ongoing compulsory care.

• History of impulse control disorder.

• Diagnosis of moderate / severe kidney failure or severe cardiovascular disease.

• Recently started psychotherapy.

• Ongoing treatment with ECT, ketamine or TMS.

• Concomitant medication or somatic disorder that would be a risk for the subject or making it difficult to evaluate efficacy of the intervention (e.g. Parkinson's disease, cancer not in remission, other drugs with similar mechanisms of action defined in protocol)

• Allergic to pramipexole

• Participation in other interventional studies

• Other factors that in the investigators opinion could influence compliance