A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder.
Adriana Feder, Sara Costi, Sarah B. Rutter, A. Collins, Usha Govindarajulu, Manish K. Jha, Sarah R. Horn, Marin Kautz, Morgan Corniquel, Katherine A. Collins, L. Bevilacqua, Andrew M. Glasgow, Jess W. Brallier, Robert H Pietrzak, James W. Murrough, Dennis S. Charney
American Journal of Psychiatry January 5, 2021 DOI: 10.1176/appi.ajp.2020.20050596 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 30 |
| Population | Individuals with chronic PTSD |
| Interventions | Ketamine Midazolam |
| Dose | 0.5 mg/kg |
| Duration | 2-week infusion period, with follow-up to assess loss of response |
| Topics | Esketamine Ketamine PTSD |
| Citations | 239 |
| Key findings | 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.
In the evidence
This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.
-
Six ketamine infusions over two weeks produced significantly greater improvement in PTSD and depression scores than midazolam, with a large effect size and a 67% responder rate.
Synthesized
-
State of the evidence: PTSD Supports
Repeated ketamine infusions significantly reduced PTSD symptom severity compared to midazolam, with a large effect size and a 67% responder rate at two weeks.
Synthesized
Comparable studies
Other randomized controlled trials on ketamine for PTSD, most cited first.