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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine how ketamine, an anesthetic, can quickly improve symptoms of Obsessive-Compulsive Disorder (OCD). Participants will receive either ketamine or midazolam, another medication, to compare their effects. The trial targets individuals with significant OCD symptoms who can pause other treatments briefly. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ketamine is generally safe and well-tolerated, even at higher doses. Some individuals have accidentally received up to ten times the usual dose without serious issues. However, about 12% of individuals may experience "emergence reactions," which are psychological effects ranging from pleasant to severe. Ketamine is already approved as a general anesthetic, which reassures about its safety in humans. This study aims to assess its safety and effectiveness for treating OCD, and additional data will clarify its safety for this specific use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for OCD?

Most treatments for Obsessive-Compulsive Disorder (OCD), like SSRIs and cognitive behavioral therapy, take weeks or even months to show significant effects. Ketamine stands out because it can potentially deliver rapid relief from OCD symptoms, often within hours or days of administration. Unlike traditional treatments that primarily target serotonin, ketamine works on the glutamate system, offering a new mechanism of action. Researchers are excited because this could mean faster and more effective relief for patients who haven't responded well to standard therapies.

What evidence suggests that this trial's treatments could be effective for OCD?

Research has shown that ketamine, which participants in this trial may receive, might quickly reduce symptoms of Obsessive-Compulsive Disorder (OCD). In one study, half of the patients who received ketamine felt better, while none in the placebo group did. Other research found that OCD symptoms dropped by nearly 50% soon after a ketamine treatment, with one patient experiencing complete symptom relief. These findings suggest that ketamine can quickly and effectively lessen OCD symptoms. Meanwhile, another group in this trial will receive midazolam, serving as an active comparator. ^{6 7 8 9 10}

Who Is on the Research Team?

Carolyn Rodriguez, MD, PhD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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, 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 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]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35267254/

Ketamine in the Treatment of Obsessive-Compulsive ... Reported data have shown a potential for fast onset of action and good tolerability of ketamine for OCD, even though the principal studies used only single- ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11760645/

Ketamine for treatment-resistant obsessive-compulsive disorder There was a 50% response rate in the group treated with ketamine compared to 0% responders in the placebo group. Significant carryover effects ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05577585

Study Details | NCT05577585 | Ketamine in OCD: Efficacy ... There will be a change of severity of obsessive and compulsive symptoms seven days after ketamine infusion compared to midazolam infusion as measured with the ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1876201820302951

Clinical utility of repeated intravenous ketamine treatment ... One patient showed a dramatic response (a drop in the YBOCS to '0') and two patients showed a partial response (25–35 % reduction in the YBOCS). Eleven patients ...

5. jnnp.bmj.com jnnp.bmj.com/content/92/8/A10.1

reviewing effects of ketamine in OCD Combined, OCD scores decline by approximately 49.7% during the first hour following intravenous ketamine administration. Furthermore, a significant reduction of ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/016812s043lbl.pdf

KETALAR (ketamine hydrochloride) injection Ketamine has a wide margin of safety; several instances of unintentional administration of overdoses of. KETALAR (up to ten times that usually required) have ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10225955/

Safety and tolerability of intramuscular and sublingual ... This study reports on adverse effects of intramuscular and sublingual ketamine dosing in a community group psychotherapy setting among 128 participants across ...

8. go.drugbank.com go.drugbank.com/drugs/DB01221

Ketamine: Uses, Interactions, Mechanism of Action Ketamine is a rapid-acting general anesthetic producing an anesthetic state characterized by profound analgesia, normal pharyngeal-laryngeal reflexes.

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2012/016812s039lbl.pdf

Ketalar Label - accessdata.fda.gov SPECIAL NOTE. EMERGENCE REACTIONS HAVE OCCURRED IN APPROXIMATELY 12 PERCENT OF PATIENTS. THE PSYCHOLOGICAL MANIFESTATIONS VARY IN SEVERITY BETWEEN PLEASANT ...

10. prevea360.com prevea360.com/DocumentLibrary/PDF/Drug-Policies/IV-Ketamine-Chronic-Pain-2300

IV Ketamine for Chronic Pain and Mental Health and ... 2.2 IV Ketamine is considered not covered due to insufficient evidence to demonstrate long-term clinical efficacy and safety for treatment of ...