Long-term Efficacy of Pramipexole in Anhedonic Depression (LONG-PRAXOL)

Long-term Efficacy and Tolerability of add-on Pramipexole for Anhedonic Depression - an Open Label Follow-up Study

The purpose of the study is to assess the long-term efficacy and safety of add-on pramipexole for treatment of patients with anhedonic depression.

Study Overview

• Status: Completed
• Conditions: Depression; Anhedonia
• Intervention / Treatment: Drug: Pramipexole

Detailed Description

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.

The aim of this open label follow-up study is to test the long-term efficacy and tolerability of add-on pramipexole in anhedonic depression. This is a continuation study of an RCT (EudraCT# 2022-001563-26) in which patients are randomized to either pramipexole or placebo for 9 weeks. After completion of the RCT, patients will be offered to participate in the current trial. Approximately 50% of the patients have been treated with pramipexole and 50% with placebo within the frames of the RCT. Patients randomized to pramipexole in the RCT will continue on their current dose and patients randomized to placebo will start pramipexole using the same dosing schedule as in the RCT. A total of 80 research subjects with unipolar depression, bipolar disorder in depressive phase, or dysthymia will be offered participation in the study after completing the RCT given that they fulfill all the inclusion criteria, and none of the exclusion criteria.

Subjects have study visits once a month during 6 months, or more often if needed based on side effects. Symptom severity, side effects and ecological momentary assessments are recorded at each study visit and dose titration schedule is modified as needed. Between study visits, research subjects may contact study personnel and the investigators can quickly arrange for an additional study visit if needed.

After the study, the decision to continue with pramipexole outside of the study or discontinue with pramipexole will be based on patient preference in combination with a willingness of the patient's regular physician to take over the treatment outside of the study.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 3

Contacts and Locations

Study Locations

• Sweden
  • Skåne County
    • Lund, Skåne County, Sweden, 221 85
      • Region Skane

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Previous participation in RCT testing the short-term efficacy of pramipexole vs placebo (EudraCT# 2022-001563-26).
• Study participants randomized to pramipexole in the RCT who wish to continue with their treatment can enrol in the study.
• Study participants randomized to placebo in the RCT who continue to fulfil the inclusion criteria (and none of the exclusion criteria) after the RCT can enrol in the study.
• The research subject has given informed consent to participate in the study.

Additional inclusion criterion for patients receiving placebo during the RCT

• Anhedonia symptoms: 3 or 4 points on ≥ 3 items of the Snaith-Hamilton Pleasure Scale (SHAPS-C). This has been adopted in previous studies as a definition of "clinically significant anhedonia".

Exclusion Criteria:

• Pregnancy, breastfeeding or planned pregnancy (if female).
• High suicide risk according to the overall clinical assessment of the research physician.
• Ongoing substance abuse (within 6 months).
• Diagnosis of current psychosis.
• Known diagnosis of Emotionally Unstable Personality Disorder.
• Treatment under LPT.
• History of impulse control disorder (including current binge-eating disorder) or a current ADHD diagnosis with hyperactivity.
• Diagnosis of intellectual disability, dementia, or other circumstance that makes it difficult to understand the meaning of participating in the trial and give informed consent.
• Diagnosis of renal failure or severe cardiovascular disease (specifically symptomatic heart failure NYHA Class II). Blood samples from RCT are sufficient to rule this out.
• Recently started psychotherapy (within 6 weeks) or planning to start such treatment during participation in the trial.
• Ongoing ECT, ketamine or rTMS treatment, excluding 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 (see section 14.5) 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, gastric bypass surgery that affects the absorption of extended release tablets.
• Known or suspected allergy to any active substance or excipient in the medicinal product included in the trial.
• Participation in other treatment studies.
• Other reason, as assessed by the investigator, that prevents the research subject's participation, such as the risk that the research subject is unable to complete the trial (non-compliance).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pramipexole; Pramipexole prolonged-release tablet with doses ranging from 0.26 mg base to 3.15 mg base / day, study duration 6 months	Drug: Pramipexole; 6 months of treatment with add-on Pramipexole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anhedonia symptoms	Total Snaith Hamilton Anhedonia Pleasure (SHAPS) self-report scale scores. Higher scores equal more severe anhedonoa. Score range 14-56	Baseline
Anhedonia symptoms	Total SHAPS self-report scores. Higher scores equal more severe anhedonoa. Score range 14-56	Month 1
Anhedonia symptoms	Total SHAPS self-report scores. Higher scores equal more severe anhedonoa. Score range 14-56	Month 2
Anhedonia symptoms	Total SHAPS self-report scores. Higher scores equal more severe anhedonoa. Score range 14-56	Month 3
Anhedonia symptoms	Total SHAPS self-report scores. Higher scores equal more severe anhedonoa. Score range 14-56	Month 4
Anhedonia symptoms	Total SHAPS self-report scores. Higher scores equal more severe anhedonoa. Score range 14-56	Month 5
Anhedonia symptoms	Total SHAPS self-report scores. Higher scores equal more severe anhedonoa. Score range 14-56	Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Core depression symptoms	Hamilton Depression Rating Scale-6 (HDRS6) scores (subscale of HDRS-17)	baseline
Core depression symptoms	HDRS6 scores (subscale of HDRS-17)	Month 1
Core depression symptoms	HDRS6 scores (subscale of HDRS-17)	Month 2
Core depression symptoms	HDRS6 scores (subscale of HDRS-17)	Month 3
Core depression symptoms	HDRS6 scores (subscale of HDRS-17)	Month 4
Core depression symptoms	HDRS6 scores (subscale of HDRS-17)	Month 5
Core depression symptoms	HDRS6 scores (subscale of HDRS-17)	Month 6
Ecological momentary assessments	Number of steps/day, movement pattern distribution over the day, walking distance, time spent in light, moderate and intense physical activity, resting heart rate, blood oxygen saturation, heart rate variability (stress scores), sleep latency (time to fall asleep), sleep awakening (how often you wake up during the night), wakefulness (time in minutes awake during a night), time in deep sleep, sleep efficiency (time asleep vs. total time in bed). All variables are measured using activity meters.	baseline
Ecological momentary assessments	By using activity meters, we will analyze relevant outcomes related to physical activity, sleep, and heart rate	Month 1
Ecological momentary assessments	By using activity meters, we will analyze relevant outcomes related to physical activity, sleep, and heart rate	Month 2
Ecological momentary assessments	By using activity meters, we will analyze relevant outcomes related to physical activity, sleep, and heart rate	Month 3
Ecological momentary assessments	By using activity meters, we will analyze relevant outcomes related to physical activity, sleep, and heart rate	Month 4
Ecological momentary assessments	By using activity meters, we will analyze relevant outcomes related to physical activity, sleep, and heart rate	Month 5
Ecological momentary assessments	By using activity meters, we will analyze relevant outcomes related to physical activity, sleep, and heart rate	Month 6
Anhedonic symptoms	Dimensional Anhedonia Rating Scale (DARS) total score	baseline
Anhedonic symptoms	Dimensional Anhedonia Rating Scale (DARS) total score	Month 1
Anhedonic symptoms	Dimensional Anhedonia Rating Scale (DARS) total score	Month 2
Anhedonic symptoms	Dimensional Anhedonia Rating Scale (DARS) total score	Month 3
Anhedonic symptoms	Dimensional Anhedonia Rating Scale (DARS) total score	Month 4
Anhedonic symptoms	Dimensional Anhedonia Rating Scale (DARS) total score	Month 5
Anhedonic symptoms	Dimensional Anhedonia Rating Scale (DARS) total score	Month 6
General depressive symptoms	Montgomery-Åsberg Depression Rating Scale (MADRS-S)	baseline
General depressive symptoms	Montgomery-Åsberg Depression Rating Scale (MADRS-S)	Month 1
General depressive symptoms	Montgomery-Åsberg Depression Rating Scale (MADRS-S)	Month 2
General depressive symptoms	Montgomery-Åsberg Depression Rating Scale (MADRS-S)	Month 3
General depressive symptoms	Montgomery-Åsberg Depression Rating Scale (MADRS-S)	Month 4
General depressive symptoms	Montgomery-Åsberg Depression Rating Scale (MADRS-S)	Month 5
General depressive symptoms	Montgomery-Åsberg Depression Rating Scale (MADRS-S)	Month 6
Sleep and insomnia	Insomnia Severity Index (ISI) total score	Baseline
Sleep and insomnia	Insomnia Severity Index (ISI) total score	Month 1
Sleep and insomnia	Insomnia Severity Index (ISI) total score	Month 2
Sleep and insomnia	Insomnia Severity Index (ISI) total score	Month 3
Sleep and insomnia	Insomnia Severity Index (ISI) total score	Month 4
Sleep and insomnia	Insomnia Severity Index (ISI) total score	Month 5
Sleep and insomnia	Insomnia Severity Index (ISI) total score	Month 6
Apathy symptoms	Apathy Evaluation Scale (AES) total score	Baseline
Apathy symptoms	Apathy Evaluation Scale (AES) total score	Month 1
Apathy symptoms	Apathy Evaluation Scale (AES) total score	Month 2
Apathy symptoms	Apathy Evaluation Scale (AES) total score	Month 3
Apathy symptoms	Apathy Evaluation Scale (AES) total score	Month 4
Apathy symptoms	Apathy Evaluation Scale (AES) total score	Month 5
Apathy symptoms	Apathy Evaluation Scale (AES) total score	Month 6
Anxiety symptoms	Generalized Anxiety Disorder 7-item scale (GAD-7)	baseline
Anxiety symptoms	Generalized Anxiety Disorder 7-item scale (GAD-7)	Month 1
Anxiety symptoms	Generalized Anxiety Disorder 7-item scale (GAD-7)	Month 2
Anxiety symptoms	Generalized Anxiety Disorder 7-item scale (GAD-7)	Month 3
Anxiety symptoms	Generalized Anxiety Disorder 7-item scale (GAD-7)	Month 4
Anxiety symptoms	Generalized Anxiety Disorder 7-item scale (GAD-7)	Month 5
Anxiety symptoms	Generalized Anxiety Disorder 7-item scale (GAD-7)	Month 6
Life quality	Brunnsviken Brief Quality of life scale (BBQ) total score	Baseline
Life quality	Brunnsviken Brief Quality of life scale (BBQ) total score	Month 1
Life quality	Brunnsviken Brief Quality of life scale (BBQ) total score	Month 2
Life quality	Brunnsviken Brief Quality of life scale (BBQ) total score	Month 3
Life quality	Brunnsviken Brief Quality of life scale (BBQ) total score	Month 4
Life quality	Brunnsviken Brief Quality of life scale (BBQ) total score	Month 5
Life quality	Brunnsviken Brief Quality of life scale (BBQ) total score	Month 6
Side effects	Number and severity of adverse events	Baseline
Side effects	Number and severity of adverse events	Month 1
Side effects	Number and severity of adverse events	Month 2
Side effects	Number and severity of adverse events	Month 3
Side effects	Number and severity of adverse events	Month 4
Side effects	Number and severity of adverse events	Month 5
Side effects	Number and severity of adverse events	Month 6
Cognitive symptoms	Change in cognitive performance using the WAIS-IV, Repeatable Battery for the Assessment of Neuropsychological Status, Delis-Kaplan Executive Function System.	6 months

Collaborators and Investigators

• Sponsor: Region Skane
• Collaborators: Lund University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2023
• Primary Completion (Actual): December 5, 2025
• Study Completion (Actual): December 5, 2025

Study Registration Dates

• First Submitted: March 23, 2023
• First Submitted That Met QC Criteria: April 10, 2023
• First Posted (Actual): April 24, 2023

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: depression; dopamine; anhedonia; pramipexole
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Behavioral Symptoms; Neurobehavioral Manifestations; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Depression; Anhedonia; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiazoles; Benzothiazoles; Azoles; Pramipexole
• Other Study ID Numbers: 2022-502270-17-00

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No