Ketamine is a promising treatment for post-traumatic stress disorder (PTSD), but further research is required to extend early findings.

To determine the short-term efficacy and tolerability of intramuscular (i.m.) ketamine compared with i.m. fentanyl for treatment-resistant PTSD symptoms.

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.

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.

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.