Repeated ketamine infusions over 2 weeks were associated with large-magnitude improvement in post-traumatic stress disorder (PTSD) symptoms compared with a psychoactive placebo in individuals with chronic PTSD. Researchers published their findings in The American Journal of Psychiatry.

“Ketamine infusions were associated with marked improvements across three of the four PTSD symptom clusters: intrusions, avoidance, and negative alterations in cognitions and mood,” wrote lead author Adriana Feder, MD, of the Icahn School of Medicine at Mount Sinai, New York, and coauthors. “In the subsample of ketamine responders, improvement in PTSD symptoms was rapid, observed 24 hours after the first infusion, and maintained for a median of 27.5 days after the primary outcome assessment day.”

A previous proof-of-concept study by the research team showed single-dose, intravenous ketamine led to a significant reduction in PTSD symptoms 24 hours after infusion. To investigate the efficacy and safety of repeated ketamine infusions, researchers conducted a randomized controlled trial of 30 patients with chronic PTSD. Participants were assigned 1:1 to receive 6 infusions of ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg), which served as a psychoactive placebo control, over 2 consecutive weeks.

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From baseline to week 2, improvement was significantly greater for the ketamine group on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and Montgomery-Åsberg Depression Rating Scale (MADRS), according to the study. In particular, the average CAPS-5 total score was 11.88 points lower in the ketamine group compared with the midazolam group.

In all, 67% of patients in the ketamine group attained treatment response compared with 20% of patients in the midazolam group, researchers reported. Ketamine infusions were well tolerated, and the study identified no serious adverse events in participants.

“This randomized controlled trial provides the first evidence of efficacy of repeated ketamine infusions in reducing symptom severity in individuals with chronic PTSD,” researchers wrote. “Further studies are warranted to understand ketamine’s full potential as a treatment for chronic PTSD."

Reference

Feder A, Costi S, Rutter SB, et al. A randomized controlled trial of repeated ketamine administration for chronic posttraumatic stress disorder. Am J Psychiatry. 2021;178(2):193-202. doi: 10.1176/appi.ajp.2020.20050596