title: Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial.
abstract: OBJECTIVE
  Few pharmacotherapies have demonstrated sufficient efficacy in the treatment of posttraumatic stress disorder (PTSD), a chronic and disabling condition.
  
  
  OBJECTIVE
  To test the efficacy and safety of a single intravenous subanesthetic dose of ketamine for the treatment of PTSD and associated depressive symptoms in patients with chronic PTSD.
  
  
  METHODS
  Proof-of-concept, randomized, double-blind, crossover trial comparing ketamine with an active placebo control, midazolam, conducted at a single site (Icahn School of Medicine at Mount Sinai, New York, New York). Forty-one patients with chronic PTSD related to a range of trauma exposures were recruited via advertisements.
  
  
  METHODS
  Intravenous infusion of ketamine hydrochloride (0.5 mg/kg) and midazolam (0.045 mg/kg).
  
  
  METHODS
  The primary outcome measure was change in PTSD symptom severity, measured using the Impact of Event Scale-Revised. Secondary outcome measures included the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impression-Severity and -Improvement scales, and adverse effect measures, including the Clinician-Administered Dissociative States Scale, the Brief Psychiatric Rating Scale, and the Young Mania Rating Scale.
  
  
  RESULTS
  Ketamine infusion was associated with significant and rapid reduction in PTSD symptom severity, compared with midazolam, when assessed 24 hours after infusion (mean difference in Impact of Event Scale-Revised score, 12.7 [95% CI, 2.5-22.8]; P = .02). Greater reduction of PTSD symptoms following treatment with ketamine was evident in both crossover and first-period analyses, and remained significant after adjusting for baseline and 24-hour depressive symptom severity. Ketamine was also associated with reduction in comorbid depressive symptoms and with improvement in overall clinical presentation. Ketamine was generally well tolerated without clinically significant persistent dissociative symptoms.
  
  
  CONCLUSIONS
  This study provides the first evidence for rapid reduction in symptom severity following ketamine infusion in patients with chronic PTSD. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with this disabling condition.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00749203.
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Adriana
authors.initials: A
authors.lastname: Feder
authors.affiliation: Department of Health Evidence and Policy, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Parides
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York3Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: James W
authors.initials: JW
authors.lastname: Murrough
authors.affiliation: Department of Anesthesiology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Perez
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Morgan
authors.affiliation: School of Public Health, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Shireen
authors.initials: S
authors.lastname: Saxena
authors.affiliation: Department of Health Evidence and Policy, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Katherine
authors.initials: K
authors.lastname: Kirkwood
authors.affiliation: Department of Psychology, University of Groningen, Groningen, the Netherlands.
authors.forename: Marije
authors.initials: M
authors.lastname: Aan Het Rot
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York3Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Kyle A B
authors.initials: KA
authors.lastname: Lapidus
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Le-Ben
authors.initials: LB
authors.lastname: Wan
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York3Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Dan
authors.initials: D
authors.lastname: Iosifescu
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York3Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York7Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at.
authors.forename: Dennis S
authors.initials: DS
authors.lastname: Charney
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D014151:Anti-Anxiety Agents / Q000627:therapeutic use; D002908:Chronic Disease; D018592:Cross-Over Studies; D003863:Depression / Q000150:complications / Q000188:drug therapy; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008874:Midazolam / Q000627:therapeutic use; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D013313:Stress Disorders, Post-Traumatic / Q000150:complications / Q000188:drug therapy*
chemical_list: D014151:Anti-Anxiety Agents; D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine; D008874:Midazolam