Ketamine for Obsessive-Compulsive Disorder

(MKET2 Trial)

Overseen By Carolyn I Rodriguez, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Must not be taking: Psychotropic, Naltrexone, Ketamine

Disqualifiers: Pregnancy, Metal in body, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

150 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to understand how ketamine works in the brain to bring about a reduction in OCD symptoms.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you must commit to medication study procedures, which might involve changes to your medication routine.

What data supports the effectiveness of ketamine as a drug for treating obsessive-compulsive disorder?

Research shows that ketamine has rapid antidepressant effects, which may help people with OCD who also have depression. Additionally, S-ketamine has been found to reduce behaviors linked to OCD in animal studies, suggesting it might have potential anti-compulsive effects. ^{1 2 3 4 5}

How is ketamine different from other drugs for OCD?

Ketamine is unique for OCD treatment because it acts rapidly by blocking NMDA receptors, which are involved in glutamate neurotransmission, a pathway linked to OCD. Unlike traditional OCD treatments that take longer to show effects, ketamine can provide quick relief, although its long-term effectiveness and safety in OCD are still under investigation. ^{2 3 5 6 7}

Eligibility Criteria

This trial is for adults aged 18-65 with Obsessive-Compulsive Disorder (OCD) who haven't improved after trying at least one standard treatment. Participants must agree to fast before sessions, not join other trials during this study, and commit to the medication procedures.

Inclusion Criteria

Meet the criteria for OCD diagnosis

I agree to fast before sessions, not join other trials, and follow medication procedures.

Able to provide informed consent

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single infusion of 0.5mg/kg of ketamine with either naltrexone or placebo, with fMRI scans before, during, and after infusion

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in OCD symptoms using the YBOCS scale

1 week

Treatment Details

Interventions

• Ketamine
• Naltrexone Pill
• Placebo pill

Trial Overview The study tests how ketamine affects OCD symptoms compared to a placebo. It also examines if blocking opioid receptors with naltrexone changes ketamine's effects. Patients are randomly given either ketamine or placebo, and some will receive naltrexone.

Participant Groups

Group I: Ketamine + Naltrexone Experimental Treatment 2 Interventions

OCD patients in this arm will receive 0.5mg/kg of ketamine - one single infusion. fMRI will be acquired before, during, and after infusion. Oral naltrexone 50 mg will be administered before the infusion.

Group II: Healthy Volunteers Active Control 1 Intervention

Healthy volunteers will have one fMRI scan visit.

Group III: Ketamine + Placebo Placebo Group 2 Interventions

OCD patients in this arm will receive 0.5mg/kg of ketamine - one single infusion. fMRI will be acquired before, during, and after infusion. An oral inactive placebo will be administered before the infusion.

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

Approved in United States as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in European Union as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in United States as Spravato for:

• Treatment-resistant depression

Approved in European Union as Spravato for:

• Treatment-resistant depression

Approved in Canada as Spravato for:

• Treatment-resistant depression

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

Oral S-ketamine was successfully used as a maintenance treatment for a patient with severe depression who did not respond to electroconvulsive therapy and deep brain stimulation, highlighting its potential efficacy in treatment-resistant cases.

The patient also had comorbid psychotic and obsessive-compulsive symptoms, suggesting that S-ketamine may be beneficial for individuals with complex mental health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral S-ketamine effective after deep brain stimulation in severe treatment-resistant depression and extensive comorbidities. Veraart, JKE., Kamphuis, J., Schlegel, M., et al.[2021]

Ketamine, while effective as a rapid antidepressant in treatment-resistant depression, showed no sustained benefits for obsessive-compulsive disorder (OCD) in a small trial of 10 subjects, with only some experiencing acute antidepressant effects.

Concerns arose regarding delayed-onset dysphoria and increased anxiety or suicidal thoughts in patients with OCD and other psychiatric issues, highlighting the need for caution and further research before using ketamine off-label in such cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two cases of delayed-onset suicidal ideation, dysphoria and anxiety after ketamine infusion in patients with obsessive-compulsive disorder and a history of major depressive disorder. Niciu, MJ., Grunschel, BD., Corlett, PR., et al.[2022]

S-ketamine significantly reduces compulsive behavior in the marble-burying test, suggesting its potential anti-compulsive effects in OCD, without affecting general locomotor activity.

The anti-compulsive effect of S-ketamine is linked to the activation of AMPA receptors and involves the ventromedial orbitofrontal cortex (vmOFC), indicating a specific mechanism of action distinct from its antidepressant effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

S-ketamine reduces marble burying behaviour: Involvement of ventromedial orbitofrontal cortex and AMPA receptors. Tosta, CL., Silote, GP., Fracalossi, MP., et al.[2019]

Oral ketamine has shown effectiveness in treating severe depression, including treatment-resistant cases and those with suicidal ideation, based on various studies including randomized controlled trials with doses ranging from 0.25 to 7 mg/kg.

Despite its lower bioavailability (20%-25% reaching the bloodstream), oral ketamine is well tolerated and can be adjusted for individual needs, making it a practical option for depression treatment alongside conventional antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

In a trial involving 10 subjects with treatment-refractory OCD, ketamine infusion did not lead to significant improvements in OCD symptoms within the first 3 days, with less than 12% reduction observed.

However, 4 out of 7 patients with comorbid depression did show a rapid antidepressant response, indicating that while ketamine may help with depression, its effects on OCD symptoms were minimal and did not persist after the initial treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of ketamine in treatment-refractory obsessive-compulsive disorder. Bloch, MH., Wasylink, S., Landeros-Weisenberger, A., et al.[2021]

Ketamine and esketamine show promise in treating disorders within the obsessive-compulsive spectrum, such as OCD, eating disorders (ED), and substance use disorders (SUD), due to their effects on glutamatergic neurotransmission, which is dysregulated in these conditions.

Despite encouraging results from numerous small studies, there is still a lack of solid evidence supporting the long-term efficacy and safety of ketamine and esketamine for these disorders, highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Potentials of Ketamine and Esketamine in Obsessive-Compulsive Disorder (OCD), Substance Use Disorders (SUD) and Eating Disorders (ED): A Review of the Current Literature. Martinotti, G., Chiappini, S., Pettorruso, M., et al.[2021]

In a 10-week clinical trial with 34 children and adolescents, N-Acetylcysteine (NAC) significantly improved symptoms of obsessive-compulsive disorder (OCD) when used alongside the SSRI citalopram, as indicated by a notable decrease in Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores.

NAC was well tolerated with no serious adverse effects reported, suggesting it is a safe adjuvant treatment for enhancing the efficacy of SSRIs in managing OCD in young patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of N-Acetylcysteine Augmentation on Obsessive Compulsive Disorder: A Multicenter Randomized Double Blind Placebo Controlled Clinical Trial. Ghanizadeh, A., Mohammadi, MR., Bahraini, S., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Oral S-ketamine effective after deep brain stimulation in severe treatment-resistant depression and extensive comorbidities. [2021]

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

Two cases of delayed-onset suicidal ideation, dysphoria and anxiety after ketamine infusion in patients with obsessive-compulsive disorder and a history of major depressive disorder. [2022]

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

S-ketamine reduces marble burying behaviour: Involvement of ventromedial orbitofrontal cortex and AMPA receptors. [2019]

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

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

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

Effects of ketamine in treatment-refractory obsessive-compulsive disorder. [2021]

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

Therapeutic Potentials of Ketamine and Esketamine in Obsessive-Compulsive Disorder (OCD), Substance Use Disorders (SUD) and Eating Disorders (ED): A Review of the Current Literature. [2021]

7. Iran pubmed.ncbi.nlm.nih.gov

Efficacy of N-Acetylcysteine Augmentation on Obsessive Compulsive Disorder: A Multicenter Randomized Double Blind Placebo Controlled Clinical Trial. [2020]