Ketamine for Obsessive-Compulsive Disorder

(MKET Trial)

Overseen By Elizabeth McCarthy

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Must not be taking: Drug interactions

Disqualifiers: Psychiatric, Neurological, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

120 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial may require you to stop taking certain medications, especially if they could interact with ketamine or increase the risk of participation. The protocol mentions a treatment-free period, which suggests you might need to stop some medications temporarily.

What evidence supports the effectiveness of ketamine for treating obsessive-compulsive disorder?

Research shows that ketamine, known for its rapid antidepressant effects, may have potential anti-compulsive effects. In a study, S-ketamine reduced marble-burying behavior, a model for obsessive-compulsive disorder, suggesting it might help with OCD symptoms. ^{1 2 3 4 5}

How does the drug ketamine differ from other treatments for obsessive-compulsive disorder?

Ketamine is unique because it acts quickly and targets glutamate, a brain chemical involved in OCD, unlike traditional treatments that often take longer to work and focus on serotonin. It is administered as an infusion, which is different from the usual oral medications. ^{1 2 4 6 7}

What is the purpose of this trial?

This trial aims to understand how ketamine quickly improves symptoms in people with Obsessive-Compulsive Disorder (OCD). Ketamine works by blocking a specific brain receptor, which helps reduce repetitive thoughts and behaviors. Recent research demonstrated that ketamine rapidly reduces OCD symptoms. The study focuses on how this process happens at different levels in the brain.

Research Team

Carolyn Rodriguez, MD, PhD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for adults aged 18-65 with a primary diagnosis of OCD who can give informed consent. Participants should have severe enough OCD symptoms to warrant the study and be able to go without other treatments for a while.

Inclusion Criteria

I can go without treatment for a while.

I understand and can agree to the study's procedures and risks.

My OCD symptoms are severe.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single infusion of either ketamine or midazolam

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 months

Treatment Details

Interventions

• Ketamine
• Midazolam

Trial Overview The study aims to understand how Ketamine, compared with Midazolam, can rapidly alleviate symptoms of OCD. Patients will receive one of these drugs and their effects on OCD improvement will be closely monitored.

Participant Groups

Group I: Ketamine Experimental Treatment 1 Intervention

OCD patients in this arm will receive 0.5mg/kg of ketamine - one single infusion

Group II: Midazolam Active Control 1 Intervention

OCD patients in this arm will receive 0.045mg/kg of midazolam - one single 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+

University of Connecticut

Collaborator

Trials

194

Recruited

162,000+

Findings from Research

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]

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]

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]

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]

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. 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]

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

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

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

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

4. England pubmed.ncbi.nlm.nih.gov

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

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

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

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]