Ketamine for treatment-resistant obsessive-compulsive disorder: Double-blind active-controlled crossover study.

Ketamine reduces obsessive-compulsive symptoms more than a psychoactive control (fentanyl) in people with severe, treatment-resistant OCD. In a small double-blind trial, participants received a single intramuscular dose of either 0.5 mg/kg ketamine, 1.0 mg/kg ketamine, or 50 µg fentanyl. Both ketamine doses produced greater and dose-related reductions on the Yale-Brown Obsessive-Compulsive Scale, with effects separating from fentanyl within 1–2 hours and persisting for up to 168 hours. Ketamine caused short-term dissociative and cardiovascular effects; two of twelve participants dropped out due to not tolerating dissociation. The findings provide preliminary evidence for ketamine's efficacy and tolerability in an outpatient cohort.

Study at a glance

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.