Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder

Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder ImportanceFew pharmacotherapies have demonstrated sufficient efficacy in the treatment of posttraumatic stress disorder (PTSD), a chronic and disabling condition. ObjectiveTo 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. Design, Setting, and ParticipantsProof-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. InterventionsIntravenous infusion of ketamine hydrochloride (0.5 mg/kg) and midazolam (0.045 mg/kg). Main Outcomes and MeasuresThe 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. ResultsKetamine 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 and RelevanceThis 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. Trial Registrationclinicaltrials.gov Identifier: NCT00749203 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Psychiatry American Medical Association

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Publisher
American Medical Association
Copyright
Copyright 2014 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.
ISSN
2168-622X
eISSN
2168-6238
DOI
10.1001/jamapsychiatry.2014.62
pmid
24740528
Publisher site
See Article on Publisher Site

Abstract

ImportanceFew pharmacotherapies have demonstrated sufficient efficacy in the treatment of posttraumatic stress disorder (PTSD), a chronic and disabling condition. ObjectiveTo 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. Design, Setting, and ParticipantsProof-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. InterventionsIntravenous infusion of ketamine hydrochloride (0.5 mg/kg) and midazolam (0.045 mg/kg). Main Outcomes and MeasuresThe 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. ResultsKetamine 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 and RelevanceThis 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. Trial Registrationclinicaltrials.gov Identifier: NCT00749203

Journal

JAMA PsychiatryAmerican Medical Association

Published: Jun 1, 2014

References

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    Strayer, RJ; Nelson, LS
  • Effects of peritraumatic ketamine medication on early and sustained posttraumatic stress symptoms in moderately injured accident victims.
    Schönenberg, M; Reichwald, U; Domes, G; Badke, A; Hautzinger, M
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    Weathers, FW; Keane, TM; Davidson, JR
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    Bremner, JD; Krystal, JH; Putnam, FW

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