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

backgroundObsessive-Compulsive Disorder (OCD) may respond to ketamine treatment.

aimTo examine the responsiveness and tolerability of treatment-refractory OCD to intramuscular (IM) ketamine compared to IM fentanyl.

methodsThis 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.

resultsTwelve 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],

conclusionsWe 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.