This randomized, double-blind, psychoactive-controlled study (n=12) compared intramuscular ketamine (35-70mg/70kg) to fentanyl (50μg) in treatment-resistant OCD patients, with 10 participants completing the trial. The study found dose-dependent reductions in OCD symptoms (Y-BOCS scores) for ketamine compared to fentanyl, with effects lasting up to 168 hours, though two participants dropped out due to dissociative effects.
Abstract of Ketamine for treatment-resistant obsessive-compulsive disorder
“Aim: To examine the responsiveness and tolerability of treatment-refractory OCD to intramuscular (IM) ketamine compared to IM fentanyl.
Methods: 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.
Results: 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.
Conclusions: 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.”
Authors: Ben Beaglehole, Paul Glue, Shona Neehoff, Shabah Shadli, Neil McNaughton, Bridget Kimber, Chrissie Muirhead, Aroha de Bie, Rachel Day-Brown & Natalie J. Hughes-Medlicott
Summary of Ketamine for treatment-resistant obsessive-compulsive disorder
Obsessive-Compulsive Disorder (OCD) is characterised by intrusive, persistent thoughts (obsessions) and repetitive behaviours (compulsions) intended to reduce anxiety or distress. The disorder affects approximately 0.5%–3% of individuals worldwide, significantly impairing quality of life, often to a degree comparable to major depression and schizophrenia. Comorbid conditions like depression and anxiety disorders are also common.
Traditional OCD treatments, such as antidepressants and psychotherapy, have limited effectiveness. Despite adequate treatment, many patients experience persistent symptoms, and around 25% do not respond to these interventions at all. Furthermore, these treatments often take weeks to show benefits, leaving a gap for faster-acting and more effective solutions.
Ketamine, an NMDA receptor antagonist, has shown promise as a rapid-acting treatment for refractory depression and other disorders. Early research on ketamine for OCD, including a single intravenous study, reported notable improvements but raised questions about optimal dosing, treatment duration, and robustness of response. Beaglehole and colleagues conducted a randomised controlled trial (RCT) to explore these aspects, comparing two doses of intramuscular (IM) ketamine to fentanyl, a psychoactive control.
Methods
Study Design
Find this paper
https://doi.org/10.1177/02698811241301215
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Cite this paper (APA)
Beaglehole, B., Glue, P., Neehoff, S., Shadli, S., McNaughton, N., Kimber, B., ... & Hughes-Medlicott, N. J. (2024). Ketamine for treatment-resistant obsessive-compulsive disorder: Double-blind active-controlled crossover study. Journal of Psychopharmacology, 02698811241301215.
Study details
Compounds studied
Ketamine
Topics studied
Obsessive-Compulsive Disorder
Study characteristics
Placebo-Controlled
Active Placebo
Double-Blind
Within-Subject
Randomized
Participants
10
Humans