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 July 2022 DOI: 10.1038/s41386-022-01266-9 (opens in new tab)
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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.
Citations in the library
Cited by 66
- Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms Neuropsychopharmacology July 24, 2023
- Treatment of Posttraumatic Stress Disorder: A State-of-the-art Review. Current Neuropharmacology 2024
- The Antidepressant Actions of Ketamine and its Enantiomers Pharmacology & Therapeutics May 1, 2023
- The Psychedelic Future of Post-Traumatic Stress Disorder Treatment Current Neuropharmacology January 5, 2024
- Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments Proceedings of the National Academy of Sciences November 27, 2023
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Cites 11
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder JAMA Psychiatry April 16, 2014
- A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression American Journal of Psychiatry April 8, 2016
- Double-Blind, Placebo-Controlled, Dose-Ranging Trial of Intravenous Ketamine as Adjunctive Therapy in Treatment-Resistant Depression (TRD) Molecular Psychiatry October 3, 2018
and 6 more in the library