A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder.
A. Feder, Sara Costi, S. Rutter, A. Collins, Usha Govindarajulu, M. Jha, S. Horn, Marin M. Kautz, M. Corniquel, K. Collins, L. Bevilacqua, Andrew Glasgow, Jess Brallier, R. Pietrzak, J. Murrough, D. Charney
American Journal of Psychiatry January 5, 2021 Peer reviewed DOI: 10.1176/appi.ajp.2020.20050596 via Semantic Scholar 239 citations
Summary
Repeated intravenous infusions of ketamine, given over two weeks, significantly reduced symptom severity in chronic PTSD compared to a psychoactive placebo (midazolam). At two weeks, the ketamine group scored nearly 12 points lower on the Clinician-Administered PTSD Scale, and 67% of participants responded to treatment versus 20% in the placebo group. Among responders, the median time to loss of response was 27.5 days after the infusion course. Ketamine was well tolerated with no serious adverse events. This is the first randomized controlled trial to show efficacy of repeated ketamine infusions for chronic PTSD.
Study at a glance
| Design | randomized controlled trial |
|---|---|
| Sample size | 30 |
| Population | individuals with chronic PTSD |
| Key finding | Repeated ketamine infusions significantly reduced PTSD symptom severity compared to midazolam, with a large effect size and a 67% responder rate at two weeks. |
Abstract
OBJECTIVE Posttraumatic stress disorder (PTSD) is a chronic and disabling disorder, for which available pharmacotherapies have limited efficacy. The authors' previous proof-of-concept randomized controlled trial of single-dose intravenous ketamine infusion in individuals with PTSD showed significant and rapid PTSD symptom reduction 24 hours postinfusion. The present study is the first randomized controlled trial to test the efficacy and safety of repeated intravenous ketamine infusions for the treatment of chronic PTSD. METHODS Individuals with chronic PTSD (N=30) were randomly assigned (1:1) to receive six infusions of ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) (psychoactive placebo control) over 2 consecutive weeks. Clinician-rated and self-report assessments were administered 24 hours after the first infusion and at weekly visits. The primary outcome measure was change in PTSD symptom severity, as assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), from baseline to 2 weeks (after completion of all infusions). Secondary outcome measures included the Impact of Event Scale-Revised, the Montgomery-Åsberg Depression Rating Scale (MADRS), and side effect measures. RESULTS The ketamine group showed a significantly greater improvement in CAPS-5 and MADRS total scores than the midazolam group from baseline to week 2. At week 2, the mean CAPS-5 total score was 11.88 points (SE=3.96) lower in the ketamine group than in the midazolam group (d=1.13, 95% CI=0.36, 1.91). Sixty-seven percent of participants in the ketamine group were treatment responders, compared with 20% in the midazolam group. Among ketamine responders, the median time to loss of response was 27.5 days following the 2-week course of infusions. Ketamine infusions were well tolerated overall, without serious adverse events. CONCLUSIONS This randomized controlled trial provides the first evidence of efficacy of repeated ketamine infusions in reducing symptom severity in individuals with chronic PTSD. Further studies are warranted to understand ketamine's full potential as a treatment for chronic PTSD.