Pramipexole to Target "Anhedonic Depression"

Phase 2

Completed

• Conditions: Dysthymia; Anhedonia; Depression, Bipolar; Depression, Unipolar
• Interventions: Drug: Pramipexole Pill

• Registration Number: NCT04121091
• Lead Sponsor: Region Skane

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-10-04
• Study First Submitted: 2019-10-04
• Study First Submitted QC: 2019-10-08
• Study First Posted: 2019-10-09
• Primary Completion: 2021-03-18
• Study Completion: 2021-03-18
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-14
• Last Update Posted: 2021-09-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

1. Age ≥18 and ≤75.
2. Diagnosis of unipolar depression; bipolar disorder in depressive phase or dysthymia.
3. Symptoms of depression; Total-score ≥ 18, measured by Montgomery-Åsberg Depression Rating Scale (MADRS).
4. Symptoms of anhedonia; Total-score < 27, measured by Dimensional Anhedonia Rating Scale (DARS).
5. Ongoing treatment with at least one antidepressant drug ≥ 4 weeks without major changes in dosage. Patients with bipolar disorder must have a mood-stabilizing drug treatment.
6. Must sign an informed consent. -

Exclusion Criteria

1. Ongoing pregnancy, breastfeeding or planning for pregnancy.
2. High suicidality assessed by the researcher with medical degree.
3. Ongoing substance use disorder (last 12 month).
4. Diagnosis of psychosis.
5. Ongoing involuntary psychiatric treatment.
6. History of Impulse-control disorder or current ADHD diagnosis.
7. Diagnosis of Intellectual disability, dementia, or other circumstances leading to difficulties to understand the implications of participating in the study and to give informed consent.
8. Diagnosis of renal failure (eGFR < 50 ml/min/1,73 m2 ) or severe cardiovascular disease (defined as symptoms of heart failure NYHA class 2).
9. Recently committed to psychotherapy (during the last 6 weeks) or planning for psychotherapy during the participation of the study.
10. Ongoing ECT-treatment.
11. Other diseases, disorders or medical treatments that according to the researchers might influence the results of the study or increases the risks of the study. Such as Parkinson's disorder, liver failure, cancer not in remission (for at least over a year).
12. Confirmed or suspected allergy to the active substance or excipients of the drug used in this study.
13. Committed to other trials
14. Other reasons that according to the researcher might prevent the subject to fulfill the obligations of the study. For example insufficient drug compliance. -

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pramipexole	Pramipexole Pill	-

Primary Outcome Measures

Name	Time	Method
Dimensional Anhedonia Rating Scale (DARS) score	baseline to week 10	Change in anhedonia symptoms (total score on the DARS). The range is 0-68, lower score indicating more severe anhedonia.

Secondary Outcome Measures

Name	Time	Method
Response/remission	baseline to week 10	Montgomery Åsberg Depression Rating Scale (MADRS) reduction 50%, MADRS ≤ 10 respectively
Montgomery Åsberg Depression Rating Scale (MADRS) score	baseline to week 10	Change in depression symptoms (total score on the MADRS)
Change in inflammatory biomarkers	baseline to week 10	The investigators will measure blood levels of Interleukin-6, C-reactive protein, Tumor Necrosis Factor Alpha, and White Blood Cell count at baseline and at study completion. The investigators will test if baseline levels and treatment-associated change in inflammatory markers can predict treatment response
Generalized Anxiety Disorder-7	baseline to week 10	Change in anxiety symptoms (total score on the the Generalized Anxiety Disorder-7 scale)
Fatigue Severity Scale	baseline to week 10	Change in fatigue symptoms (total score on the the Fatigue Severity scale)
The Apathy Evaluation Scale	baseline to week 10	Change in apathy symptoms (total score on the the The Apathy Evaluation Scale)
Change in brain imaging parameters	baseline to week 10 (and baseline data as potential predictor)	Structural imaging, followed by resting-state functional imaging, diffusion tensor imaging and thereafter the monetary incentive delay task
Snaith-Hamilton Anhedonia Pleasure Scale	baseline to week 10	Change in anhedonia symptoms (total score on the Snaith-Hamilton Anhedonia Pleasure Scale)
the Motivation and Pleasure Scale	baseline to week 10	Change in motivation/anhedonia symptoms (total score on the the Motivation and Pleasure Scale)
Insomnia Severity Index	baseline to week 10	Change in insomnia symptoms (total score on the the Insomnia Severity Index scale)

Trial Locations

Locations (1)

Psychiatry Clinic, Lund, Region Skåne; 🇸🇪 Lund, Sweden