Ketamine for Depression in Parkinson's Disease

(KET-PD Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Sophie E. Holmes, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Yale University

Disqualifiers: Dementia, Suicidal ideation, Substance dependence, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing if ketamine can help reduce depression in people with Parkinson's disease. The study will use brain scans to see if ketamine changes brain activity and increases connections between brain cells. Researchers hope that these changes will lead to less severe depression symptoms. Ketamine has been studied for its potential effects on depression and other symptoms in Parkinson's disease.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team to get a clear answer based on your specific situation.

What data supports the effectiveness of the drug Ketamine Infusion for depression in Parkinson's Disease?

Research shows that low-dose ketamine infusions can reduce depression and improve symptoms in Parkinson's disease patients, as well as in those with treatment-resistant depression. Additionally, animal studies suggest ketamine can reverse depressive-like behaviors and memory issues in Parkinson's models. ^{1 2 3 4 5}

Is ketamine safe for treating depression in Parkinson's disease?

Ketamine has a known safety profile and is generally well tolerated when administered by trained professionals, with mild side effects like brief changes in blood pressure, heart rate, or respiratory rate. Long-term safety is not fully understood, but even extended use has not been associated with significant adverse effects, and it has been used safely for depression and pain in various forms. ^{4 6 7 8 9}

How does the drug ketamine differ from other treatments for depression in Parkinson's disease?

Ketamine is unique because it is administered as a low-dose infusion and acts quickly to reduce depression and improve motor symptoms in Parkinson's disease by desynchronizing abnormal brain activity, unlike traditional antidepressants that may take weeks to show effects. ^{4 5 10 11 12}

Research Team

Sophie E. Holmes, PhD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for people aged 40-80 with Parkinson's Disease (stages 1-3) and major depression, who don't have dementia or other serious medical conditions. Participants must not use drugs of abuse, agree to contraception if applicable, and be willing to follow the study plan.

Inclusion Criteria

Stated willingness to comply with all study procedures and availability for the duration of the study

I have been diagnosed with major depression and scored at least 15 on a depression scale.

I have Parkinson's disease at stage 1, 2, or 3.

Exclusion Criteria

A primary psychiatric disorder (as determined by the MINI) except for MDD

My blood pressure is not controlled and is often 140/90 mmHg or higher.

Contraindications to MRI scanning

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 6 infusions of ketamine or placebo over 3 weeks, with continuous cardiac monitoring and oximetry

3 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in depression severity and various physiological measures

4-5 weeks

2 visits (in-person)

Treatment Details

Interventions

• Ketamine Infusion (NMDA Receptor Antagonist)
• Placebo - Saline Infusion (Other)

Trial Overview The trial tests repeated doses of ketamine infusion against a saline placebo in those with Parkinson's Disease to see if it helps with depression. Some participants will also get brain scans before and after treatment to look at changes related to ketamine's effects.

Participant Groups

Group I: Ketamine Infusion Experimental Treatment 1 Intervention

Participants will receive 6 infusions of ketamine (0.5 mg/kg IV, up to 60 mg total) , administered over 40 minutes while on continuous cardiac monitoring and oximetry

Group II: Saline Infusion Placebo Group 1 Intervention

Participants will receive 6 infusions of placebo (saline IV), administered over 40 minutes while on continuous cardiac monitoring and oximetry

Ketamine Infusion is already approved in Canada for the following indications:

Approved in Canada as Ketamine for:

• Anesthesia
• Pain management

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Nancy J. Brown

Yale University

Chief Medical Officer since 2020

MD from Yale School of Medicine

Peter Salovey

Yale University

Chief Executive Officer since 2013

PhD in Psychology from Yale University

Fox (Michael J.) Foundation for Parkinson's Research

Collaborator

Trials

2

Recruited

100+

Findings from Research

Oral ketamine shows a significant antidepressant effect in patients with major depressive disorder, with a standardized mean difference of -0.75 based on a meta-analysis of 3 randomized controlled trials involving 161 participants.

The study found no significant increase in side effects when comparing oral ketamine to placebo, suggesting it is well-tolerated, but the remission and response rates were only marginally better than placebo, indicating the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Update on the Efficacy and Tolerability of Oral Ketamine for Major Depression: A Systematic Review and Meta-Analysis. Nuñez, NA., Joseph, B., Pahwa, M., et al.[2021]

In a case series of five inpatients with major depressive disorder and suicidal ideation, six infusions of ketamine led to an impressive 84% reduction in suicidal ideation scores and a 47% reduction in depression scores over approximately 12 days.

The study suggests that serial ketamine infusions are safe and feasible for reducing suicidal thoughts and depressive symptoms, although the small sample size highlights the need for larger randomized controlled trials to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine augmentation for major depressive disorder and suicidal ideation: Preliminary experience in an inpatient psychiatry setting. Sinyor, M., Williams, M., Belo, S., et al.[2022]

In a series of 5 case studies, low-dose subanesthetic intravenous ketamine infusion demonstrated long-lasting benefits in Parkinson's disease patients, including reduced l-DOPA-induced dyskinesia, improved on time, and decreased depression.

The findings suggest that low-dose ketamine may work by desynchronizing abnormal brain activity, similar to deep brain stimulation, indicating its potential as a safe and effective treatment that warrants further investigation in controlled clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Reports Showing a Long-Term Effect of Subanesthetic Ketamine Infusion in Reducing l-DOPA-Induced Dyskinesias. Sherman, SJ., Estevez, M., Magill, AB., et al.[2020]

A single intravenous infusion of ketamine has been shown to provide rapid but temporary relief from symptoms of treatment-resistant major depressive disorder (MDD) and bipolar depression, indicating its potential as a quick intervention for severe cases.

While generally safe and well tolerated when administered by trained professionals, concerns exist regarding the long-term side effects, including dissociative symptoms and risk of abuse, highlighting the need for standardized treatment guidelines for ketamine use in psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine for Treatment-Resistant Mood Disorders. Park, LT., Falodun, TB., Zarate, CA.[2023]

Subcutaneous (SC) administration of racemic ketamine and esketamine has shown rapid and robust antidepressant effects in both unipolar and bipolar patients, with response and remission rates ranging from 50% to 100% after single or multiple doses.

The studies indicated that SC ketamine is generally well-tolerated, with only transitory side effects, making it a promising and cost-effective treatment option for depression, especially in developing countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous Ketamine in Depression: A Systematic Review. Cavenaghi, VB., da Costa, LP., Lacerda, ALT., et al.[2021]

Oral ketamine appears to be well tolerated for treating treatment-resistant depression, especially when administered over longer periods, although the overall quality of studies on its antidepressant effects is low.

Current research suggests that while intravenous ketamine shows short-term success in major depressive disorder, more rigorous studies are needed to evaluate the long-term effects and side effects of all ketamine administration routes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral ketamine for the treatment of pain and treatment-resistant depression†. Schoevers, RA., Chaves, TV., Balukova, SM., et al.[2022]

In a study of 66 patients with treatment-resistant bipolar depression, repeated intravenous ketamine infusions led to significant reductions in depressive symptoms, with an average decrease of 6.08 points on the Quick Inventory for Depression Symptomatology-Self Report-16 scale after four infusions.

The treatment was generally well tolerated, with only 4.5% of patients experiencing treatment-emergent hypomania, and no cases of mania or psychosis, indicating a favorable safety profile for ketamine in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world effectiveness of repeated ketamine infusions for treatment-resistant bipolar depression. Fancy, F., Rodrigues, NB., Di Vincenzo, JD., et al.[2023]

References

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

Effectiveness and Safety of Ketamine for Unipolar Depression: a Systematic Review. [2021]

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

An Update on the Efficacy and Tolerability of Oral Ketamine for Major Depression: A Systematic Review and Meta-Analysis. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Ketamine augmentation for major depressive disorder and suicidal ideation: Preliminary experience in an inpatient psychiatry setting. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Case Reports Showing a Long-Term Effect of Subanesthetic Ketamine Infusion in Reducing l-DOPA-Induced Dyskinesias. [2020]

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

Ketamine reversed short-term memory impairment and depressive-like behavior in animal model of Parkinson's disease. [2022]

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

Ketamine for depression: where do we go from here? [2021]

7. Finland pubmed.ncbi.nlm.nih.gov

Ketamine as treatment for depression. [2018]

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

Oral Ketamine for Depression, 1: Pharmacologic Considerations and Clinical Evidence. [2019]

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

Ketamine for Treatment-Resistant Mood Disorders. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Subcutaneous Ketamine in Depression: A Systematic Review. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Oral ketamine for the treatment of pain and treatment-resistant depression†. [2022]

12. Denmark pubmed.ncbi.nlm.nih.gov

Real-world effectiveness of repeated ketamine infusions for treatment-resistant bipolar depression. [2023]