Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial.
Chadi G. Abdallah, John D Roache, Ralitza Gueorguieva, Lynnette A. Averill, Stacey Young-McCaughan, Paulo R Shiroma, Prerana Purohit, Antoinette Brundige, William Murff, Kyung-Heup Ahn, Mohamed Sherif, Eric J Baltutis, Mohini Ranganathan, Deepak C D'Souza, Brenda Martini, Steven M. Southwick, Ismene L. Petrakis, Rebecca R Burson, Kevin B Guthmiller, Argelio L López-roca, Karl A Lautenschlager, John P McCallin, Matthew B Hoch, Alexandar Timchenko, Sergio E Souza, Charles E Bryant, Jim Mintz, Brett T Litz, Douglas E Williamson, Terence M Keane, Alan L Peterson, John H. Krystal
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology July 2022 DOI: 10.1038/s41386-022-01266-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 158 |
| Population | Veterans and service members with PTSD who had failed previous antidepressant treatment |
| Interventions | Ketamine Placebo |
| Dose | 0.2 mg/kg (low dose) or 0.5 mg/kg (standard dose), 8 infusions administered twice weekly |
| Duration | 8 infusions over 4 weeks, with follow-up for 4 weeks after the last infusion |
| Measures | PTSD Checklist for DSM-5 (PCL-5), Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), Montgomery Åsberg Depression Rating Scale (MADRS) |
| Topics | Esketamine Ketamine PTSD |
| Registration | NCT02655692 |
| Key findings | Repeated intravenous ketamine infusions did not significantly reduce PTSD symptoms on the PCL-5 or CAPS-5 at either the 0.2 mg/kg or 0.5 mg/kg dose compared with placebo. The standard 0.5 mg/kg dose did significantly reduce depression on the MADRS, and side effects were dose-related, short-lived, and well tolerated. |
Abstract
This study tested the efficacy of repeated intravenous ketamine doses to reduce symptoms of posttraumatic stress disorder (PTSD). Veterans and service members with PTSD (n = 158) who failed previous antidepressant treatment were randomized to 8 infusions administered twice weekly of intravenous placebo (n = 54), low dose (0.2 mg/kg; n = 53) or standard dose (0.5 mg/kg; n = 51) ketamine. Participants were assessed at baseline, during treatment, and for 4 weeks after their last infusion. Primary analyses used mixed effects models. The primary outcome measure was the self-report PTSD Checklist for DSM-5 (PCL-5), and secondary outcome measures were the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the Montgomery Åsberg Depression Rating Scale (MADRS). There were no significant group-by-time interactions for PTSD symptoms measured by the PCL-5 or CAPS-5. The standard ketamine dose ameliorated depression measured by the MADRS significantly more than placebo. Ketamine produced dose-related dissociative and psychotomimetic effects, which returned to baseline within 2 h and were less pronounced with repeated administration. There was no evidence of differential treatment discontinuation by ketamine dose, consistent with good tolerability. This clinical trial failed to find a significant dose-related effect of ketamine on PTSD symptoms. Secondary analyses suggested that the standard dose exerted rapid antidepressant effects. Further studies are needed to determine the role of ketamine in PTSD treatment. ClinicalTrials.gov identifier: NCT02655692.
Comparable studies
Other randomized controlled trials on ketamine for PTSD, most cited first.