TY - JOUR
T1 - Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military
T2 - a double-blind, randomized, placebo-controlled multi-center clinical trial
AU - Abdallah, Chadi G.
AU - Roache, John D.
AU - Gueorguieva, Ralitza
AU - Averill, Lynnette A.
AU - Young-McCaughan, Stacey
AU - Shiroma, Paulo R.
AU - Purohit, Prerana
AU - Brundige, Antoinette
AU - Murff, William
AU - Ahn, Kyung Heup
AU - Sherif, Mohamed A.
AU - Baltutis, Eric J.
AU - Ranganathan, Mohini
AU - D’Souza, Deepak
AU - Martini, Brenda
AU - Southwick, Steven M.
AU - Petrakis, Ismene L.
AU - Burson, Rebecca R.
AU - Guthmiller, Kevin B.
AU - López-Roca, Argelio L.
AU - Lautenschlager, Karl A.
AU - McCallin, John P.
AU - Hoch, Matthew B.
AU - Timchenko, Alexandar
AU - Souza, Sergio E.
AU - Bryant, Charles E.
AU - Mintz, Jim
AU - Litz, Brett T.
AU - Williamson, Douglas E
AU - Keane, Terence M.
AU - Peterson, Alan L
AU - Krystal, John H.
N1 - Funding Information:
Full details of the study methods were previously reported [15]. Briefly, this double-blind, randomized, controlled trial enrolled Veterans and active duty service members with PTSD symptoms from three centers. It was supported jointly by the US Department of Defense and the US Department of Veterans Affairs as part of the Consortium to Alleviate PTSD (CAP). All study procedures were approved and monitored by an Institutional Review Board at each study site as well as the CAP Data and Safety Monitoring Board and the US Army Medical Research and Development Command Human Research Protection Office. All participants provided written informed consent prior to enrollment. ClinicalTrials. gov identifier: NCT02655692.
Funding Information:
This research was supported by Consortium to Alleviate PTSD (CAP) award numbers W81XWH-13-2-0065 from the US Department of Defense, Defense Health Program, Psychological Health and Traumatic Brain Injury Research Program (PH/TBI RP), and I01CX001136-01 from the US Department of Veterans Affairs, Office of Research & Development, Clinical Science Research & Development Service, and the VA National Center for PTSD. Salary for Dr. Abdallah was partially supported by the Beth K. and Stuart C. Yudofsky Chair in the Neuropsychiatry of Military Post Traumatic Stress Syndrome at the Baylor College of Medicine.
Publisher Copyright:
© 2022, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85123252864&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85123252864&partnerID=8YFLogxK
U2 - 10.1038/s41386-022-01266-9
DO - 10.1038/s41386-022-01266-9
M3 - Article
AN - SCOPUS:85123252864
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
SN - 0893-133X
ER -