Pramipexole for Anhedonic Depression

NCT05355337 | Completed Phase 3 DMC

• 2 other identifiers: 2021-06876-012022-001563-26
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief 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 randomized controlled trials (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.

Conditions

Psychiatric Disorders Mood; Anhedonia; Depression

Keywords

Pramipexole

Outcome Measures

Primary Outcomes (1)

• Effect on anhedonia symptoms

  Change in Snaith-Hamilton Pleasure Scale (SHAPS) self-report total score from baseline to week 9. Higher scores equal more severe anhedonoa. Score range 14-56

  9 weeks

Secondary Outcomes (44)

• Effect on core depression symptoms

  9 weeks

• Effect on other anhedonic domains not measured by SHAPS

  9 weeks

• Effect on general depressive symptoms

  9 weeks

• Effect on sleep disturbances

  9 weeks

• Effect on apathy symptoms

  9 weeks

Study Arms (3)

Pramipexole

ACTIVE COMPARATOR

Pramipexole prolonged-release tablet, 0.26 mg base to 3.15 mg base / day for 9 weeks (individually varying dose titrating during these weeks).

Drug: Pramipexole

Placebo

PLACEBO COMPARATOR

Tablets in appearance identical to the active comparator tablets, but without the the active substance (pramipexole).

Drug: Placebo

Healthy controls

NO INTERVENTION

40 healthy controls who will carry out blood sampling, lumbar puncture and fMRI according to the same protocol as the depressed patients.

Interventions

Pramipexole DRUG

9 weeks of treatment with Pramipexole

Pramipexole

Placebo DRUG

9 weeks of treatment with Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 years and 75 years.
• Informed consent
• Diagnosis of unipolar depressive episode or bipolar disorder in depressive phase or dysthymia.
• Clinically significant anhedonia symptoms: SHAPS self-report score 3 or 4 on ≥ 3 items.
• Ongoing stable treatment with at least one antidepressant or mood stabilizing medication for at least 4 weeks. Has tried an antidepressant at a therapeutic dose but not achieved remission (refractory stage 1 depression)

You may not qualify if:

• Ongoing pregnancy, breastfeeding or planned pregnancy.
• High risk of suicide according to the overall clinical assessment of the research physician.
• Substance abuse within the last 6 months.
• Diagnosis of current psychotic disorder.
• Known diagnosis of Emotionally unstable personality disorder.
• Ongoing treatment under the Compulsory Psychiatric Care Act.
• Medical history or strong clinical suspicion of impulse control disorder (including current binge-eating disorder) or a current Attention Deficit Hyperactivity Disorder diagnosis with hyperactivity.
• Diagnosis of intellectual disability, dementia, or other circumstances that makes it difficult to understand the meaning of participating in the trial and provide informed consent.
• Diagnosis of renal failure (eGFR \< 50 ml/min/1.73m2) or severe cardiovascular disease (specifically symptomatic heart failure New York Heart Association Class II or greater).
• Recently started psychotherapy (within 6 weeks) or planning to start such treatment during participation in the trial.
• Ongoing treatment with electroconvulsive therapy (ECT), ketamine or repetitive transcranial magnetic stimulation (rTMS), except maintenance ECT, ketamine or rTMS. (Maintenance treatment is defined as the use of ECT/ketamine/rTMS for a period exceeding 3 months after a series of ECT/ketamine/rTMS treatment in order to prevent the onset of a new episode.
• Other medical conditions or other concomitant drug treatment which, in the opinion of the investigators, may affect the evaluability of the trial or conditions that increase trial risk. For example, Parkinson's disease, hepatic insufficiency, ongoing cancer not in remission for more than one year, obesity surgery affecting the absorption of extended-release tablets.
• Ongoing treatment with drugs that affect plasma levels of pramipexole or have similar or antagonistic mechanism of action as pramipexole are not allowed. Ongoing treatment with neuroleptics are not allowed except for low-dose quetiapine 27 (≤150 mg/day) since it has very low binding to dopamine receptors at such low doses.
• Known or suspected allergy to any active substance or excipient in the medicinal product included in the trial.
• Participation in other treatment studies

Sponsors & Collaborators

• Region Skane: lead
• Lund University: collaborator

Study Sites (1)

Region Skåne

Lund, Skåne County, 221 85, Sweden

Location

Related Publications (1)

• Lindahl J, Asp M, Stahl D, Tjernberg J, Eklund M, Bjorkstrand J, van Westen D, Jensen J, Mansson K, Tornberg A, Svensson M, Deierborg T, Ventorp F, Lindqvist D. Add-on pramipexole for anhedonic depression: study protocol for a randomised controlled trial and open-label follow-up in Lund, Sweden. BMJ Open. 2023 Nov 30;13(11):e076900. doi: 10.1136/bmjopen-2023-076900.

  PMID: 38035737 DERIVED

MeSH Terms

Conditions

Mood Disorders; Anhedonia; Depression

Interventions

Pramipexole

Condition Hierarchy (Ancestors)

Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Benzothiazoles; Thiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized placebo-controlled with two arms plus one arm of healthy controls with no intervention

Study Record Dates

• First Submitted: April 19, 2022
• First Posted: May 2, 2022
• Study Start: February 8, 2023
• Primary Completion: June 4, 2025
• Study Completion: June 4, 2025
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)