@article{139936c7b61c4a0fb9d85baf739c3dc2,
title = "A randomized controlled trial of repeated ketamine administration for chronic posttraumatic stress disorder",
abstract = "Objective: Posttraumatic stress disorder (PTSD) is a chronic and disabling disorder, for which available pharmacotherapies have limited efficacy. The authors' previous proofof- 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 {\AA}sberg 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.",
author = "Adriana Feder and Sara Costi and Rutter, {Sarah B.} and Collins, {Abigail B.} and Usha Govindarajulu and Jha, {Manish K.} and Horn, {Sarah R.} and Marin Kautz and Morgan Corniquel and Collins, {Katherine A.} and Laura Bevilacqua and Glasgow, {Andrew M.} and Jess Brallier and Pietrzak, {Robert H.} and Murrough, {James W.} and Charney, {Dennis S.}",
note = "Funding Information: Supported by an Independent Investigator Award from the Brain and Behavior Research Foundation (principal investigator, Dr. Feder), Technology Development Awards from Mount Sinai Innovation Partners and the Mount Sinai i3 Accelerator, and a donation from Mr. Gerald Greenwald and Mrs. Glenda Greenwald. Additional funding for this study was provided by the Ehrenkranz Laboratory for Human Resilience, a component of the Depression and Anxiety Center for Discovery and Treatment at ISMMS. Funding Information: The authors thank the research pharmacists and the Clinical Research Unit and Psychiatry Department nursing personnel at ISMMS for their extensive work on this research. The authors also thank the members of the Mount Sinai Ketamine Data and Safety Monitoring Board/Ketamine Oversight Committee for their assistance and study oversight, as well as all of the patients who volunteered to participate in the study. ClinicalTrials.gov identifier: NCT02397889. Drs. Feder and Charney are co-inventors on an issued patent in the United States and several issued patents outside of the United States, filed by the Icahn School of Medicine at Mount Sinai (ISMMS) for the use of ketamine as therapy for posttraumatic stress disorder; this intellectual property has not been licensed. Dr. Jha has received contract research grant support from Acadia Pharmaceuticals and Janssen Research and Development and honoraria for CME presentations from the North American Center for ContinuingMedicalEducationandGlobalMedicalEducation.Dr.K.Collins is a paid independent rater for Medavante-Prophase. Dr. Murrough has provided consultation services or served on advisory boards for Allergan, Boehreinger Ingelheim, Clexio Biosciences, Fortress Biotech, FSV7, Global Medical Education, Impel Neuropharma, Janssen Research and Development, Medavante-Prophase, Novartis, Otsuka, and Sage Therapeutics. Dr. Murrough is also a co-inventor on a patent application filed by ISMMS for the use of ezogabine and other KCNQ channel openers to treat depression and related conditions; this intellectual property has not been licensed. Drs. Murrough and Charney are co-inventors on a patent application filed by ISMMS for the use of intranasally administered neuropeptide Y for the treatment of mood and anxiety disorders; this intellectual property has not been licensed. Dr. Charney is co-inventor on several issued U.S. patents, and several pending U.S. patent applications, filed by ISMMS for the use of ketamine as therapy for treatment-resistant depression and suicidal ideation. ISMMS has entered into a licensing agreement with Janssen Pharmaceuticals and receives payments from Janssen under the license agreement related to these patents; as a co-inventor, Dr. Charney is entitled to a portion of the payments received by the ISMMS. Because esketamine has received regulatory approval for treatment-resistant depression, ISMMS and Dr. Charney, as an employee andaco-inventor,willbeentitledtoadditionalpaymentsunderthelicense agreement. Dr. Charney is also a co-inventor on several patents filed by ISMMS for a cognitive training intervention to treat depression and related psychiatric disorders. ISMMS has entered into a licensing agreement with Click Therapeutics and receives payments related to the use of this cognitivetraininginterventionforthetreatmentofpsychiatricdisorders.In accordance with the ISMMS Faculty Handbook, Dr. Charney has received a portion of these payments and is entitled to a portion of any additional payments that the medical school might receive from this license with Click Therapeutics. The other authors report no financial relationships with commercial interests. Publisher Copyright: {\textcopyright} 2021 American Psychiatric Association. All rights reserved.",
year = "2021",
month = feb,
day = "1",
doi = "10.1176/appi.ajp.2020.20050596",
language = "English (US)",
volume = "178",
pages = "193--202",
journal = "American Journal of Psychiatry",
issn = "0002-953X",
publisher = "American Psychiatric Association",
number = "2",
}