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

Trial Summary

What is the purpose of this trial?

This trial tests if pramipexole can help adults with anxiety or depression feel more socially connected. Pramipexole increases dopamine levels in the brain, which may improve how people respond to positive social interactions. The study will measure brain activity, behavior, and self-reported feelings before and after a period of treatment. Pramipexole has shown potential to improve mood and reduce anxiety in both experimental and clinical settings.

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.

What data supports the effectiveness of the drug Pramipexole for anxiety and depression?

Research shows that Pramipexole, a drug that affects dopamine receptors in the brain, has been effective in treating depression in people with Parkinson's disease and has shown promise in treating unipolar and bipolar depression. It has been used successfully as an add-on therapy for patients who do not respond to traditional antidepressants. ^{1 2 3 4 5}

Is pramipexole generally safe for humans?

Pramipexole, used for Parkinson's disease and restless legs syndrome, is generally well tolerated but may have some side effects related to its action on dopamine receptors. It has been studied for safety in various conditions, including depression, and is known to have some dopaminergic side effects, which are effects related to the brain's dopamine system. ^{4 5 6 7 8}

How is the drug pramipexole unique in treating anxiety and depression?

Pramipexole is unique because it primarily targets the D3 dopamine receptor, which is different from most traditional antidepressants. This mechanism, along with its neuroprotective and anti-inflammatory properties, makes it a novel option for treatment-resistant depression. ^{4 5 6 8 9}

Research Team

Charles Taylor, PhD

Principal Investigator

University of California, San Diego

Franklin Schneier, MD

Principal Investigator

New York State Psychiatric Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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]

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 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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Pain and depression in Parkinson's disease: new therapeutic possibilities of pramipexole]. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Pramipexole for stage 2 treatment-resistant major depression: an open study. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Pramipexole in the treatment of unipolar and bipolar depression. A systematic review and meta-analysis. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Classics in Chemical Neuroscience: Pramipexole. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Pramipexole Augmentation for Treatment-Resistant Unipolar and Bipolar Depression in the Real World: A Systematic Review and Meta-Analysis. [2023]

7. Russia (Federation) pubmed.ncbi.nlm.nih.gov

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

8. New Zealand pubmed.ncbi.nlm.nih.gov

Role of pramipexole in the management of Parkinson's disease. [2021]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Beneficial effect of pramipexole for motor function and depression in Parkinson's disease. [2021]