Pramipexole to Target "Anhedonic Depression"

• Pramipexole Pill (Drug): Add-on pramipexole

Primary outcomes

• 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 outcomes

• Response [baseline to week 10]: Montgomery Åsberg Depression Rating Scale (MADRS). The range is 0-60, lower score indicating less general depressive symptoms. Response definition: reduction of at least 50% Remission definition: MADRS total score equal to or below 10
• Montgomery Åsberg Depression Rating Scale (MADRS) Score [baseline to week 10]: Change in depression symptoms (total score on the MADRS). The range is 0-60, lower score indicating less general depressive symptoms.
• Snaith-Hamilton Anhedonia Pleasure Scale [baseline to week 10]: Change in anhedonia symptoms (total score on the Snaith-Hamilton Anhedonia Pleasure Scale) score 0-1-2-3. Range 0-32. Higher score indicating more intense anhedonic symptoms.
• Generalized Anxiety Disorder-7 [baseline to week 10]: Change in anxiety symptoms (total score on the the Generalized Anxiety Disorder-7 scale = GAD-7). Range 0-21. Higher score indicating more anxiety.
• Insomnia Severity Index [baseline to week 10]: Change in insomnia symptoms (total score on the the Insomnia Severity Index scale = ISI). Range 0-28. Higher score indicating more insomnia symptoms.
• Fatigue Severity Scale [baseline to week 10]: Change in fatigue symptoms (total score on the the Fatigue Severity scale = FSS). Range 9-63. Higher score indicating more fatigue.
• The Apathy Evaluation Scale [baseline to week 10]: Change in apathy symptoms (total score on the the The Apathy Evaluation Scale = AES). Range 0-54. Higher score indicating more severe apathy.
• Change in Inflammatory Biomarkers [baseline to week 10]: The investigators will measure blood levels of Interleukin-6 (IL-6), C-reactive protein (CRP), Tumor Necrosis Factor Alpha (TNF), and White Blood Cell count (WBC) at baseline and at study completion. The investigators will test if baseline levels and treatment-associated change in inflammatory markers can predict treatment response
• Participation in fMRI With MID-task [baseline to week 10 (and baseline data as potential predictor)]: fMRI = functional magnetic resonance tomography. Structural imaging, followed by resting-state functional imaging, diffusion tensor imaging and thereafter the MID (monetary incentive delay) task.

Sex: All, ages: 18 Years to 75 Years

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. -

Participant flow

Outcome results

• Dimensional Anhedonia Rating Scale (DARS) Score (Primary), Mean, score on a scale: Pramipexole 15.75 +/- 6.440
• Response (Secondary), Count of participants, Participants: Pramipexole 4
• Montgomery Åsberg Depression Rating Scale (MADRS) Score (Secondary), Mean, score on a scale: Pramipexole 26.33 +/- 4.185
• Snaith-Hamilton Anhedonia Pleasure Scale (Secondary), Mean, score on a scale: Pramipexole 30.00 +/- 5.592
• Generalized Anxiety Disorder-7 (Secondary), Mean, score on a scale: Pramipexole 9.64 +/- 6.087
• Insomnia Severity Index (Secondary), Mean, score on a scale: Pramipexole 15.73 +/- 6.182
• Fatigue Severity Scale (Secondary), Mean, score on a scale: Pramipexole 46.45 +/- 12.581
• The Apathy Evaluation Scale (Secondary), Mean, score on a scale: Pramipexole 52.55 +/- 6.905
• Change in Inflammatory Biomarkers (Secondary), Mean, mg/L: Pramipexole 3.8 +/- 4.7
• Participation in fMRI With MID-task (Secondary), Count of participants, Participants: Pramipexole 8

Adverse events

Time frame: For each participant, adverse event data was collected for 14 weeks: every week for 10 weeks and an additional check-up at week 14.

Other adverse events by term

Limitations and caveats: Inherent limitations and caveats of this test-of-feasibility study: small-scale (small sample) and open-label design.

• Study Protocol and Statistical Analysis Plan (PDF, 2019-06-17)

NIH grants: 2019