Pramipexole for Anxiety and Depression

Recruiting at 2 trial locations

Overseen By Taylor Smith, B.S.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Diego

Must not be taking: SSRIs, Benzodiazepines, others

Disqualifiers: Suicide risk, Bipolar, Psychotic disorders, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 6 weeks

108 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether pramipexole, a medication, can improve social interactions and functioning in individuals with anxiety or depression. Participants will undergo a 6-week treatment period, receiving either pramipexole or a placebo (a non-active pill) to compare outcomes. The study aims to understand how targeting the brain's dopamine system might reduce feelings of social disconnection. This trial may suit those with noticeable anxiety or depression who struggle in social settings and are not currently using certain medications or treatments for their condition. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Do I need to stop taking my current medications to join the trial?

Yes, you will need to stop taking any psychotropic medications (like SSRIs or benzodiazepines) at least 14 days before joining the study, except for fluoxetine, which requires a 30-day period. You cannot use these medications during the study.

Is there any evidence suggesting that pramipexole is likely to be safe for humans?

Research shows that pramipexole is generally safe for use. This medication commonly treats Parkinson’s disease and restless leg syndrome, alleviating symptoms like stiffness and shaking. Some individuals taking pramipexole have reported mild side effects such as nausea, dizziness, or fatigue.

Earlier studies found that pramipexole works by affecting the dopamine system in the brain, which plays a crucial role in mood and movement. While pramipexole is approved for other conditions, its use for anxiety and depression remains under investigation. Although some safety information exists from its use in other treatments, further studies are necessary to fully understand its effects on anxiety and depression.

Participants should discuss any concerns with their doctors and monitor their well-being during treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for anxiety and depression?

Pramipexole is unique because it offers a new approach to treating anxiety and depression by targeting the dopamine system. Unlike traditional treatments that primarily focus on serotonin reuptake, pramipexole is a dopamine agonist, which means it activates dopamine receptors directly. This could potentially lead to quicker symptom relief for patients who don't respond well to current therapies like SSRIs or SNRIs. Researchers are excited about its potential to address treatment-resistant cases and offer a fresh alternative for those seeking different options.

What evidence suggests that pramipexole might be an effective treatment for anxiety and depression?

Research has shown that pramipexole can help reduce symptoms of depression. In people with Parkinson's disease, a review of 18 studies found that pramipexole improved mood. Other studies suggest it might also help those with bipolar depression. Some trials showed significant improvements in depression after 12 weeks, but these results were not always statistically significant. However, benefits appeared over a longer period. This trial will compare different dosages of pramipexole, specifically 1 mg/d and 2.5 mg/d, to a placebo. Pramipexole affects dopamine, a brain chemical related to mood and reward, which might improve social interactions in people with anxiety and depression. ^{6 7 8 9 10}

Who Is on the Research Team?

Franklin Schneier, MD

Principal Investigator

New York State Psychiatric Institute

Charles Taylor, PhD

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

This trial is for adults aged 18-50 who are struggling with depression, anxiety, or feeling socially isolated. Participants must be able to undergo brain scans (fMRI) and commit to a 6-week study period. The trial excludes individuals outside this age range or those unable to complete the required assessments.

Inclusion Criteria

English proficiency

Below the normative mean for temperamental reward sensitivity (ATQ - Approach < 32)

Moderate or greater social disability assessed with self-rating (SDS - Social ≥ 5)

Exclusion Criteria

I have a close family member with schizophrenia, bipolar disorder, or another psychotic disorder.

I do not have severe health issues that could worsen by joining this study.

History of impulse control problems (e.g., pathological gambling)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pramipexole or placebo in a 6-week randomized, double-blind, placebo-controlled trial

6 weeks

Baseline and week 6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pramipexole

Trial Overview The trial is testing if pramipexole can help people feel more connected by improving social functioning. It's a double-blind study, meaning neither participants nor researchers know who gets the real pill or placebo. Assessments will be done at the start and after six weeks using fMRI scans and questionnaires.

How Is the Trial Designed?

Group I: Pramipexole 2.5 mg/d Active Control 1 Intervention

Each participant will take pramipexole in identical capsular form twice daily for 6 weeks.

Group II: Pramipexole 1 mg/d Active Control 1 Intervention

Each participant will take pramipexole in identical capsular form twice daily for 6 weeks.

Group III: Placebo Placebo Group 1 Intervention

Each participant will take placebo in identical capsular form twice daily for 6 weeks.

Pramipexole is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Mirapex for:

• Parkinson's disease
• Restless Legs Syndrome

Approved in European Union as Mirapexin for:

• Parkinson's disease
• Restless Legs Syndrome

Approved in Canada as Sifrol for:

• Parkinson's disease
• Restless Legs Syndrome

Approved in Japan as Glepark for:

• Parkinson's disease
• Restless Legs Syndrome

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

New York State Psychiatric Institute

Collaborator

Trials

481

Recruited

154,000+

Published Research Related to This Trial

Pramipexole shows a significant effect size (0.6-1.1) in treating both bipolar and unipolar depression, with a low short-term rate of manic switching (1% mania, 5% hypomania) in bipolar patients, making it a promising option for treatment-resistant cases.

While pramipexole is neuroprotective and improves sleep architecture, it is associated with rare but serious side effects, including sleep attacks, compulsive behaviors, and psychosis, highlighting the need for further safety evaluations in psychiatric populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pramipexole in psychiatry: a systematic review of the literature. Aiken, CB.[2018]

In a study of 36 nondemented Parkinson's disease patients, pramipexole (PPX) significantly improved depressive symptoms as measured by the Hamilton Depression Rating Scale after 3 months of treatment.

PPX not only helped reduce depression in patients with mild depressive symptoms but also improved overall motor function, suggesting it has both antidepressant and motor-enhancing effects in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial effect of pramipexole for motor function and depression in Parkinson's disease. Kano, O., Ikeda, K., Kiyozuka, T., et al.[2021]

Pramipexole, a non-ergot dopamine agonist, is effective in treating both the motor and non-motor symptoms of Parkinson's disease, including depression, and is now available in an extended-release formulation for improved compliance and continuous effect over 24 hours.

While pramipexole is generally well tolerated, it has a higher incidence of certain dopaminergic side effects compared to traditional levodopa treatment, which should be considered when evaluating the benefit-risk ratio for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of pramipexole in the management of Parkinson's disease. Antonini, A., Barone, P., Ceravolo, R., et al.[2021]

Pramipexole shows promise as an effective treatment for unipolar and bipolar depression, with a short-term response rate of 52.2% and a long-term response rate of 62.1% based on a systematic review of 13 studies involving 504 participants.

Patients taking pramipexole had a significantly better response rate compared to those on placebo, while its efficacy was comparable to that of traditional SSRIs, indicating it could be a valuable alternative for those who do not respond to standard antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pramipexole in the treatment of unipolar and bipolar depression. A systematic review and meta-analysis. Tundo, A., de Filippis, R., De Crescenzo, F.[2022]

In a study involving 66 patients with Parkinson's disease, the dopamine receptor antagonist mirapex was found to be effective in improving emotional disorders (like anxiety and depression), cognitive disturbances, and sleep disorders when used alongside standard Parkinson's treatments.

Patients with emotional and cognitive disorders received an average dose of 3.5 mg daily, while those with sleep disorders received 2.9 mg daily, and both groups showed significant improvements as assessed by various psychometric scales and neuropsychological tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Mirapex (pramipexole) in the treatment of non-motor disturbances in Parkinson's disease]. Nodel', MR., Iakhno, NN.[2018]

Pramipexole, a dopamine agonist, shows promise as an effective augmentation treatment for patients with treatment-resistant depression, achieving a pooled treatment response rate of 62.5% across 8 studies involving 281 patients.

The safety profile of pramipexole is favorable, with nausea and somnolence being the most common side effects, suggesting it could be a viable option for both unipolar and bipolar depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pramipexole Augmentation for Treatment-Resistant Unipolar and Bipolar Depression in the Real World: A Systematic Review and Meta-Analysis. Tundo, A., Betro', S., de Filippis, R., et al.[2023]

In a study of 78 patients with Parkinson's disease, treatment with the dopamine receptor agonist pramipexole for 3 months significantly reduced pain intensity by 48.2% during 'on-periods' and 23.7% during 'off-periods', indicating its efficacy in managing pain associated with motor complications.

The therapy also led to a significant decrease in depression scores from 15.2 to 10.4, suggesting that pramipexole not only helps with pain but also improves mood in patients with Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pain and depression in Parkinson's disease: new therapeutic possibilities of pramipexole]. Letvinenko, IV., Odinak, MM., Mogil'naia, VI.[2018]

In a study of 10 patients with treatment-resistant major depressive disorder, adding pramipexole to their existing antidepressant therapy resulted in significant improvement in depression scores, with a mean reduction of 11.4 points on the MADRS scale.

60% of participants showed a positive response to treatment, indicating that pramipexole may be an effective adjunctive therapy, although two patients experienced mild side effects leading to early termination of the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pramipexole for stage 2 treatment-resistant major depression: an open study. Inoue, T., Kitaichi, Y., Masui, T., et al.[2018]

Pramipexole is a dopamine D2-like receptor agonist, specifically preferring the D3 receptor, which is important for treating both motor and psychiatric symptoms in conditions like Parkinson's disease and restless leg syndrome.

It is approved for managing symptoms of idiopathic Parkinson's disease and moderate to severe primary restless leg syndrome, highlighting its therapeutic potential in neurological disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Classics in Chemical Neuroscience: Pramipexole. Wilson, SM., Wurst, MG., Whatley, MF., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11428619/

Comparative Short- and Long-Term Effectiveness ... A meta-analysis of 18 randomized controlled trials showed that pramipexole improves depressive symptoms in patients with Parkinson's disease [21] ...

2. secure.medicalletter.org secure.medicalletter.org/TML-article-1739c

Adjunctive Pramipexole for Treatment-Resistant Depression Data from observational studies suggest that pramipexole can be effective in patients with bipolar depression,7 but a recently published double- ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06269146

NCT06269146 | Pramipexole to Enhance Social Connections This study seeks to understand if the medication pramipexole improves social connectedness and functioning in adults (ages 18-50) who experience anxiety or ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39829389/

A randomised double-blind, placebo-controlled trial of ... Clinically large, but statistically non-significant, effects of pramipexole on depression at 12 weeks, with significant longer-term benefits on mood and ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0165178122006011

The effectiveness of off-label dopamine stimulating agents ... Dopamine agonists such as pramipexole have already been proven effective in reducing depressive symptoms in Parkinson's disease (Bxarone et al., 2010), a ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/pramipexole-oral-route/description/drg-20065603

Pramipexole (oral route) - Side effects & dosage Pramipexole is a dopamine agonist that works on the nervous system to help treat the symptoms of Parkinson disease.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/022421s022lbl.pdf

Mirapex ER - accessdata.fda.gov Symptoms including apathy, anxiety, depression, fatigue, insomnia, sweating, and pain have been reported during taper or after discontinuation of dopamine ...

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK557539/

Pramipexole - StatPearls - NCBI Bookshelf - NIH Pramipexole is a medication used in the management and treatment of Parkinsonism and restless leg syndrome. It is in the anti-parkinsonian class of drugs.

9. drugs.com drugs.com/mtm/pramipexole.html

Pramipexole Uses, Side Effects & Warnings Pramipexole is used to treat symptoms of Parkinson's disease (stiffness, tremors, muscle spasms, and poor muscle control).

10. reference.medscape.com reference.medscape.com/drug/mirapex-mirapex-er-pramipexole-343048

Mirapex, Mirapex ER - pramipexole (Rx) pramipexole and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to ...