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EFFECTS OF KETAMINE ON EXPLICIT AND IMPLICIT SUICIDAL COGNITION: A RANDOMIZED CONTROLLED TRIAL IN TREATMENT-RESISTANT DEPRESSION

Authors

  • Rebecca B. Price Ph.D.,

    1. Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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  • Dan V. Iosifescu M.D.,

    1. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York
    2. Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York
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  • James W. Murrough M.D.,

    1. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York
    2. Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York
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  • Lee C. Chang M.D.,

    1. Department of Anesthesiology, Baylor College of Medicine, Houston, Texas
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  • Rayan K. Al Jurdi M.D.,

    1. Mental Health Care Line, Michael E. Debakey VA Medical Center, Houston, Texas
    2. Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas
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  • Syed Z. Iqbal M.D.,

    1. Mental Health Care Line, Michael E. Debakey VA Medical Center, Houston, Texas
    2. Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas
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  • Laili Soleimani M.D.,

    1. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York
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  • Dennis S. Charney M.D.,

    1. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York
    2. Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York
    3. Pharmacology & Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York
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  • Alexandra L. Foulkes M.S.,

    1. Mental Health Care Line, Michael E. Debakey VA Medical Center, Houston, Texas
    2. Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas
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  • Sanjay J. Mathew M.D.

    Corresponding author
    1. Mental Health Care Line, Michael E. Debakey VA Medical Center, Houston, Texas
    2. Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas
    • Correspondence to: Sanjay J. Mathew, M.D., Michael E. Debakey VA Medical Center & Baylor College of Medicine, Houston, Texas 77030. E-mail: sjmathew@bcm.edu

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  • Contract grant sponsor: Evotec, Janssen Pharmaceuticals, and Avanir, by NIMH Career Development Award 1K23 MH-094707, and by grant UL1 TR000067 from the NIH National Center for Advancing Translational Sciences (to J.W.M.); Contract grant sponsor: Icahn School of Medicine at Mount Sinai from AstraZeneca, Brainsway, Euthymics, Neosync, and Roche and CNS Response, Otsuka, Servier, and Sunovion (to D.V.I.); Contract grant sponsor: NIH, NIH/NIMH, NARSAD, and USAMRAA (to D.S.C.); Contract grant sponsor: AstraZeneca, Bristol-Myers Squibb, Naurex, Roche, Genentech, and NIMH grant RO1 MH-081870, by the Department of Veterans Affairs (VA), by a NARSAD Independent Investigator Award and funding from the Brown Foundation, Inc. (to S.J.M.); Contract grant sponsor: Career Development Award from NIMH (1K23MH100259) (to R.B.P.).

Abstract

Background

Preliminary evidence suggests intravenous ketamine has rapid effects on suicidal cognition, making it an attractive candidate for depressed patients at imminent risk of suicide. In the first randomized controlled trial of ketamine using an anesthetic control condition, we tested ketamine's acute effects on explicit suicidal cognition and a performance-based index of implicit suicidal cognition (Implicit Association Test; IAT) previously linked to suicidal behavior.

Method

Symptomatic patients with treatment-resistant unipolar major depression (inadequate response to ≥3 antidepressants) were assessed using a composite index of explicit suicidal ideation (Beck Scale for Suicidal Ideation, Montgomery-Asberg Rating Scale suicide item, Quick Inventory of Depressive Symptoms suicide item) and the IAT to assess suicidality implicitly. Measures were taken at baseline and 24 hr following a single subanesthetic dose of ketamine (n = 36) or midazolam (n = 21), a psychoactive placebo agent selected for its similar, rapid anesthetic effects. Twenty four hours postinfusion, explicit suicidal cognition was significantly reduced in the ketamine but not the midazolam group.

Results

Fifty three percent of ketamine-treated patients scored zero on all three explicit suicide measures at 24 hr, compared with 24% of the midazolam group (χ2 = 4.6; P = .03). Implicit associations between self- and escape-related words were reduced following ketamine (P = .01; d = .58) but not midazolam (P = .68; d = .09). Ketamine-specific decreases in explicit suicidal cognition were largest in patients with elevated suicidal cognition at baseline, and were mediated by decreases in nonsuicide-related depressive symptoms.

Conclusions

Intravenous ketamine produces rapid reductions in suicidal cognition over and above active placebo. Further study is warranted to test ketamine's antisuicidal effects in higher-risk samples.

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