Ketamine for treatment-resistant obsessive-compulsive disorder: Double-blind active-controlled crossover study.
Ben Beaglehole, Paul Glue, Shona Neehoff, Shabah M. Shadli, Neil McNaughton, Bridget Kimber, Chrissie Muirhead, Aroha de Bie, Rachel Day-Brown, Natalie J Hughes-Medlicott
Journal of Psychopharmacology 2025 DOI: 10.1177/02698811241301215 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized double-blind psychoactive-controlled study Peer reviewed |
|---|---|
| Sample size | 12 |
| Population | Adults aged 18–50 with severe treatment-resistant OCD |
| Interventions | Ketamine Fentanyl Ondansetron |
| Dose | 0.5 mg/kg, 1.0 mg/kg, 50 µg |
| Duration | Single dose, outcomes measured up to 168 hours |
| Topics | Ketamine Esketamine |
| Keywords | Mental health OCD Obsessive-Compulsive Disorder Ketamine therapy Clinical trials Psychiatric treatment |
| Citations | 12 |
| Key points | Both 0.5 mg/kg and 1.0 mg/kg intramuscular ketamine produced greater and dose-related reductions in OCD symptoms than the psychoactive control fentanyl, with effects lasting up to 168 hours. |
Abstract
Obsessive-Compulsive Disorder (OCD) may respond to ketamine treatment. To examine the responsiveness and tolerability of treatment-refractory OCD to intramuscular (IM) ketamine compared to IM fentanyl. This was a randomised double-blind psychoactive-controlled study with single doses of racemic ketamine 0.5 mg/kg, 1.0 mg/kg or fentanyl 50 µg (psychoactive control). Pre-dosing with 4 mg oral ondansetron provided nausea prophylaxis. Eligible participants were aged between 18 and 50 years with severe treatment-resistant OCD. The primary efficacy measure was the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Tolerability was measured with the Clinician-Administered Dissociative States Scale (CADSS). Repeated measures analysis of variance with orthogonal polynomial trends was used to assess the effect of drug treatment on Y-BOCS and CADSS scores. Twelve participants were randomised and 10 completed the study (7 females, 3 males, mean age 33 years). Two participants dropped out due to not tolerating dissociative effects associated with the study medication. The reductions in Y-BOCS scores were greater and statistically dose-related for both ketamine doses than fentanyl (dose [linear], F(1, 9) = 6.5, p = 0.031). Score changes for all treatments were maximal at 1-2 h with a steady separation of scores out to 168 h. Ketamine was associated with short-term dissociative and cardiovascular effects. We provide further preliminary evidence for the efficacy and tolerability of IM ketamine in an outpatient cohort of OCD. Additional work is required to establish the optimal dosing regimen and longer-term role of ketamine for OCD. These findings are encouraging given the well-known limitations that exist for treatments in this area.
Comparable studies
Other randomized controlled trials on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community | 1994 | Randomized controlled trial | n = 19 |
| Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode | 2013 | Randomized controlled trial | n = 73 |
| Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery | 2005 | Randomized controlled trial | n = 75 |
| Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures | 2014 | Randomized controlled trial | n = 41 |
| Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers | 2000 | Single-blind placebo-controlled study | n = 20 |
Citations in the library
Cited by 10
- Six weeks open-label oral ketamine for patients with treatment-resistant depression, post-traumatic stress disorder, or obsessive-compulsive disorder. Journal of Psychopharmacology June 5, 2025
- Intranasal Esketamine Augmentation in Treatment-Resistant Obsessive–Compulsive Disorder with Comorbid Treatment-Resistant Depression: A Six-Month Case Report Psychiatry International September 10, 2026
- Ketamine Dose and Duration Effects in Internalizing Disorders The Journal of Clinical Pharmacology September 1, 2026
- Ketamine for the Treatment of Obsessive-Compulsive Disorder (OCD): A Systematic Review on Efficacy and Tolerability. Clinical Neuropharmacology June 19, 2026
- Ketamine Dosing Across Clinical Indications: A Narrative Review Organized by Proposed NMDA-Related Mechanisms. The Journal of Clinical Pharmacology June 1, 2026
and 5 more in the library
Cites 7
- Measurement of dissociative states with the Clinician‐Administered Dissociative States Scale (CADSS) Journal of Traumatic Stress 1998
- Blinding and expectancy confounds in psychedelic randomized controlled trials Expert Review of Clinical Pharmacology May 26, 2021
- Brain Changes Associated With Long-Term Ketamine Abuse, A Systematic Review Frontiers in Neuroanatomy March 18, 2022
- Ketamine and psychotherapy for the treatment of psychiatric disorders: systematic review BJPsych Open May 1, 2023
- Oral ketamine for depression: An updated systematic review The World Journal of Biological Psychiatry January 18, 2023
and 2 more in the library