Ketamine for treatment-resistant post-traumatic stress disorder: double-blind active-controlled randomised crossover study

Abstract

BACKGROUND: Ketamine is a promising treatment for post‐traumatic stress disorder (PTSD), but further research is required to extend early findings. AIMS: To determine the short‐term efficacy and tolerability of intramuscular (i.m.) ketamine compared with i.m. fentanyl for treatment‐resistant PTSD symptoms. METHOD: We completed a randomised double‐blind psychoactive‐controlled study with single doses of i.m. racemic ketamine 0.5 mg/kg or 1.0 mg/kg or i.m. fentanyl 50 μg (psychoactive control). Eligible participants were aged between 18 and 50 years old and had treatment‐refractory PTSD. The primary efficacy measure was the Impact of Events Scale ‐ Revised (IESR), and tolerability was measured with the Clinician‐Administered Dissociative States Scale. Analysis of variance with dose and time as repeated measures was used to assess the effects of drug treatment on total IESR and Clinician‐Administered Dissociative States Scale scores. RESULTS: Thirty‐three participants completed the study (26 females, mean age 34.5 years). Ketamine, particularly at 1 mg/kg, was associated with substantially reduced IESR ratings, with some effect remaining after 1 week. Ketamine was also associated with short‐term dissociative and cardiovascular effects. CONCLUSIONS: We provide preliminary support for the efficacy and tolerability of i.m. ketamine in a community sample of individuals with PTSD. Further work is required to establish the optimal dosing regimen and longer‐term role of ketamine in treatment of PTSD, but our findings are encouraging given the well‐known of treatments in this area.