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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

Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder

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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
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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 Psychiatry – American Medical Association

Published: Jun 1, 2014

References

  • Posttraumatic stress disorder in the National Comorbidity Survey.
    Kessler, RC; Sonnega, A; Bromet, E; Hughes, M; Nelson, CB
  • Trauma and posttraumatic stress disorder in the community: the 1996 Detroit Area Survey of Trauma.
    Breslau, N; Kessler, RC; Chilcoat, HD; Schultz, LR; Davis, GC; Andreski, P
  • Pharmacotherapy of PTSD: premises, principles, and priorities.
    Ravindran, LN; Stein, MB
  • Pharmacotherapy for posttraumatic stress disorder: review with clinical applications.
    Jeffreys, M; Capehart, B; Friedman, MJ
  • The role of the glutamatergic system in posttraumatic stress disorder.
    Nair, J; Singh Ajit, S
  • New perspectives in glutamate and anxiety.
    Riaza Bermudo-Soriano, C; Perez-Rodriguez, MM; Vaquero-Lorenzo, C; Baca-Garcia, E
  • A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression.
    Zarate, CA; Singh, JB; Carlson, PJ
  • Ketamine for treatment-resistant unipolar depression: current evidence.
    Mathew, SJ; Shah, A; Lapidus, K
  • Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial.
    Murrough, JW; Iosifescu, DV; Chang, LC
  • Anaesthesia for urological endoscopic procedures in adult outpatients.
    Fabbri, LP; Batacchi, S; Linden, M
  • Adverse events associated with ketamine for procedural sedation in adults.
    Strayer, RJ; Nelson, LS
  • Clinical and sensorimotor gating effects of ketamine in normals.
    Duncan, EJ; Madonick, SH; Parwani, A
  • Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses.
    Krystal, JH; Karper, LP; Seibyl, JP
  • 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
  • Ketamine aggravates symptoms of acute stress disorder in a naturalistic sample of accident victims.
    Schönenberg, M; Reichwald, U; Domes, G; Badke, A; Hautzinger, M
  • The correlation between ketamine and posttraumatic stress disorder in burned service members.
    McGhee, LL; Maani, CV; Garza, TH; Gaylord, KM; Black, IH
  • Acute stress symptoms do not worsen in posttraumatic stress disorder and abuse with a single subanesthetic dose of ketamine.
    Zeng, MC; Niciu, MJ; Luckenbaugh, DA
  • Transient resolution of treatment-resistant posttraumatic stress disorder following ketamine infusion.
    D’Andrea, D; Andrew Sewell, R
  • Clinician-administered PTSD scale: a review of the first ten years of research.
    Weathers, FW; Keane, TM; Davidson, JR
  • A new depression scale designed to be sensitive to change.
    Montgomery, SA; Asberg, M
  • The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression.
    Rush, AJ; Trivedi, MH; Ibrahim, HM
  • Sequenced treatment alternatives to relieve depression (STAR*D): rationale and design.
    Rush, AJ; Fava, M; Wisniewski, SR
  • Measurement of dissociative states with the Clinician-Administered Dissociative States Scale (CADSS).
    Bremner, JD; Krystal, JH; Putnam, FW
  • The Brief Psychiatric Rating Scale (BPRS): recent developments in ascertainment and scaling.
    Overall, JE; Gorham, DR
  • A rating scale for mania: reliability, validity and sensitivity.
    Young, RC; Biggs, JT; Ziegler, VE; Meyer, DA
  • Core symptoms of posttraumatic stress disorder unimproved by alprazolam treatment.
    Braun, P; Greenberg, D; Dasberg, H; Lerer, B
  • Clonazepam for treatment of sleep disturbances associated with combat-related posttraumatic stress disorder.
    Cates, ME; Bishop, MH; Davis, LL; Lowe, JS; Woolley, TW
  • The discovery of chlordiazepoxide and the clinical introduction of benzodiazepines: half a century of anxiolytic drugs.
    López-Muñoz, F; Alamo, C; García-García, P
  • Approaches to developing new anxiolytics and antidepressants.
    Dubovsky, SL
  • Pharmacological treatment of PTSD—established and new approaches.
    Steckler, T; Risbrough, V
  • Repeated stress causes cognitive impairment by suppressing glutamate receptor expression and function in prefrontal cortex.
    Yuen, EY; Wei, J; Liu, W; Zhong, P; Li, X; Yan, Z
  • Synaptic dysfunction in depression: potential therapeutic targets.
    Duman, RS; Aghajanian, GK
  • mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists.
    Li, N; Lee, B; Liu, RJ
  • Glutamate N-methyl-d-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure.
    Li, N; Liu, RJ; Dwyer, JM