Pramipexole vs Placebo Treatment in Bipolar Disorder With Anhedonic Depression

NCT07664852 | Not Yet Recruiting Phase 3

• 1 other identifier: 2026-526383-20-00
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 1

Brief Summary

Among psychiatric disorders, bipolar disorder stands out due to its alarmingly high suicide rates. This condition presents unique management challenges, especially during its depressive phase, which carries the highest risk of suicide. B-HAPPI is an academic randomized controlled trial to evaluate a new medication for bipolar depression. It will investigate the efficacy and safety of pramipexole, a potent dopamine agonist that has demonstrated significant effectiveness in bipolar disorder in preliminary studies, showing large effect sizes.

• Population: 126 patients with bipolar depression
• Intervention: Pramipexole added to ongoing treatment with mood stabilizer, flexible dosing - target dose 2.1 mg/day
• Control: Add-on identical placebo
• Outcomes: Primary outcome is change in anhedonia symptoms between baseline and 6 weeks of intervention. Key secondary outcomes include (for example) general depression symptoms and safety measures. There will be a 15 weeks open label follow up. If shown to be effective and safe, this intervention could become a key treatment option for bipolar depression, reducing suffering and potentially lowering suicide risk.

Conditions

Bipolar Disorder (BD)

Keywords

Randomized controlled trial; Pramipexole; Dopamine agonist; Anhedonia

Outcome Measures

Primary Outcomes (1)

• Change in Snaith-Hamilton Pleasure Scale (SHAPS) self-reported total score after 6 weeks of treatment compared to baseline

  14 items rated from points with 1 to 4. Higher scores equal more severe anhedonia. Score range: 14-56.

  Between baseline visit and week 6

Secondary Outcomes (13)

• Change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to week 6 and week 21

  Between baseline visit and week 21

• Change in sedentary behaviour (SED) between baseline, week 6 and week 21

  Between baseline and week 21

• Change in light physical activity (LPA) between baseline, week 6 and week 21

  Between baseline and week 21

• Change in moderate- to vigorous physical activity (MVPA) between baseline, week 6 and week 21

  Between baseline and week 21

• Change in Dimensional Anhedonia Rating Scale (DARS) from baseline to week 6 and 21

  Between baseline visit and week 21

Other Outcomes (9)

• Clinical improvement per structured clinical assessments

  Between baseline visit and week 21

• Digital neuropsychological test battery

  Between baseline visit and week 21

• Changes in Blood-oxygen-level dependent imaging (BOLD) activity

  Between baseline and week 6

Study Arms (2)

Pramipexole-treated

EXPERIMENTAL

6 weeks of treatment with the dopamine agonist pramipexole adjunctive to a mood stabilizer. Target dose 2.1 mg base/day.

Drug: Pramipexole

Placebo-treated

PLACEBO COMPARATOR

6 weeks of treatment with placebo adjunctive to a mood stabilizer.

Drug: Placebo

Interventions

Pramipexole DRUG

6 weeks of treatment with the dopamine agonist pramipexole adjunctive to a mood stabilizer. Target dose 2.1 mg base/day.

Pramipexole-treated

Placebo DRUG

6 weeks of treatment with a placebo for the dopamine agonist pramipexole adjunctive to a mood stabilizer.

Placebo-treated

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant has given their written consent to participate in the trial.
• For WOCBP, adequate contraception should be used (see section 9.6) and a negative pregnancy test is (u-hCG) required. WOCBP: For the purpose of this protocol, a woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
• Age ≥18 years ≤80 years.
• Diagnosis of bipolar disorder type I or II as verified by ICD-11.
• Ongoing depressive state according to ICD-11 (at least 2 weeks, maximum 18 months).
• Significant anhedonia, defined as 3 or 4 points on ≥3 items on the SHAPS self-rating scale
• Minimum score on the MADRS expert rating scale ≥ 20
• Ongoing treatment with at least one mood stabilising agent (with sufficient antimanic protection as determined by clinical judgment). If treatment with lithium is ongoing, serum levels must be within the reference range of 0.4-0.9. The latest concentration measurement should be within one month before treatment initiation. If treatment is ongoing with a mood stabilising anticonvulsant or an antipsychotic, any dose adjustments made within 4 weeks prior to study start must be reported. Mood-stabilising anticonvulsants and antipsychotics must not be newly initiated within 4 weeks prior to study start. If treatment with antidepressants is ongoing the dose must have been stable for at least 4 weeks.

You may not qualify if:

• Pregnancy, breastfeeding or planned pregnancy (if female). See also section 8.6 below for clarification.
• Meets criteria for a mixed episode according to ICD-11.
• High suicide risk according to the overall clinical assessment of the research physician.
• Ongoing substance abuse (within 6 months).
• Ongoing psychotic symptoms.
• Prior diagnosis of schizophrenia or schizoaffective disorder.
• Clinical presentation is primarily attributable to a personality disorder.
• Subject to compulsory psychiatric care (LPT).
• Diagnosis of intellectual disability, dementia, cognitive impairment, or other conditions (including those related to the depressive disorder itself) that, in the judgment of the study physician, may substantially impair the participant's ability to understand the study and provide informed consent.
• Diagnosis of renal failure (eGFR \<50 ml/min/1.73m2) or severe cardiovascular disease (specifically symptomatic heart failure \>Class II New York Heart Association (NYHA)).
• Ongoing treatment with ECT, ketamine or rTMS.
• Other medical conditions, other ongoing interventions or other concomitant drug treatment (see section 7.3) that, 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.
• 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 participant's participation, such as the risk that the research participant is unable to complete the trial (non-compliance).

Sponsors & Collaborators

• Daniel Lindqvist: lead

Study Sites (1)

Adult Psychiatry

Lund, Skåne County, 22240, Sweden

Location

MeSH Terms

Conditions

Bipolar Disorder; Anhedonia

Interventions

Pramipexole

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Daniel Lindqvist, PhD, MD

  Region Skåne, Lund University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mirjam Wolfschlag, PhD

CONTACT

+46724596431; mirjam_katharina.wolfschlag@med.lu.se

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of Psychiatry Division and research, Principal Investigator, Senior Consultant

Study Record Dates

• First Submitted: June 17, 2026
• First Posted: June 24, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: July 1, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)