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

Abstract

<p><b>Background:</b> Obsessive-Compulsive Disorder (OCD) may respond to ketamine treatment.</p> <p><b>Aim:</b> To examine the responsiveness and tolerability of treatment-refractory OCD to intramuscular (IM) ketamine compared to IM fentanyl.</p> <p><b>Methods:</b> This was a randomised double-blind psychoactive-controlled study with single doses of racemic ketamine 0.5mg/kg, 1.0mg/kg or fentanyl 50µg (psychoactive control). Pre-dosing with 4mg 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.</p> <p><b>Results:</b> Twelve participants were randomised and 10 completed the study (7 females, 3 males, mean age 33years). 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], <i>F</i>(1, 9) =6.5, <i>p</i>=0.031). Score changes for all treatments were maximal at 1–2h with a steady separation of scores out to 168h. Ketamine was associated with short-term dissociative and cardiovascular effects.</p> <p><b>Conclusions:</b> 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.</p>