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Cited by 345Treatment of Major DepressionSuicide and Self-Harm StudiesElectroconvulsive Therapy Studies

EFFECTS OF KETAMINE ON EXPLICIT AND IMPLICIT SUICIDAL COGNITION: A RANDOMIZED CONTROLLED TRIAL IN TREATMENT-RESISTANT DEPRESSION: Effects of ketamine on suicidality

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Price, Rebecca B., Iosifescu, Dan V., Murrough, James W., Chang, Lee C., Al Jurdi, Rayan K., Iqbal, Syed Z., Soleimani, Laili, Charney, Dennis S. +2 more·2014·Depression and Anxiety
DOI 10.1002/da.22253PMC PMC4112410
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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 (χ(2) = 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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  • Ketamine reduced suicidal ideation within 1-4 hours in major depression.

    “Ketamine, an NMDA glutamate receptor antagonist, reduced suicidal ideation within 1–4 hours in major depression(71–75) and bipolar disorder.(76, 77)”

    From Improving Suicide Prevention Through Evidence-Based Strategies: A Systematic Review (2021) · cites this paper as [71]

    The Introduction reports earlier findings suggesting that ketamine can reduce suicidal ideation within 40 minutes, including in treatment-resistant depression. This trial studied patients with treatment-resistant unipolar major depression but measured its suicidal-ideation outcome at 24 hours, not at 1–4 hours; the claimed interval is therefore not established by this trial. (LLM, conf=0.80)

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  • Ketamine rapidly induces flexibility in implicit representations of self on the Implicit Association Test.

    “Ketamine rapidly induces flexibility in implicit representations of self on the Implicit Association Test 134,135 , and these shifts correlated with self-reported symptom improvements 110 , suggesting that ketamine can immediately impact the structure of implicit mental representations relevant to one's concept of self, a core form of cognitive bias in depression.”

    From Neuroplasticity in cognitive and psychological mechanisms of depression: an integrative model (2020) · cites this paper as [134]

    The Methods (Implicit Association Test) describe measures of implicit associations between “Me” and escape or death. The Results (Primary Outcomes) report a reduction in “Escape = Me” associations 24 hours after ketamine, but not in “Death = Me” associations; the ketamine–midazolam comparison for these implicit measures was not significant. Thus the paper supports a rapid change in one measured self-association, but not the broader claim that ketamine induces flexibility in implicit representations of self. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Several versions of the IAT have been incorporated into clinical ketamine trials, which found that the "escape" version of the IAT was associated with reductions in SI.

    “Critically, several versions of the IAT have also been incorporated into clinical ketamine trials, which found that the “escape” version of the IAT (instead of “death,” the participant links the self with “escape” or “stay”) was associated with reductions in SI (57, 58).”

    From New methods for assessing rapid changes in suicide risk (2021) · cites this paper as [58]

  • A single infusion of ketamine reduces explicit suicidal cognition and a performance-based index of implicit suicidal cognition compared with another anesthetic, although mediated by depressive symptom improvement.

    “This is partially supported by the finding of a single infusion of ketamine reducing explicit suicidal cognition and a performance-based index of implicit suicidal cognition compared with another anesthetic, although it was mediated by depressive symptom improvement.181”

    From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [181]

  • Potential dose-dependent opposing actions of ketamine in cognition and cognitive symptoms could be analogous to amphetamines.

    “These potential dose-dependent opposing actions of ketamine in CCS could be analogous to amphetamines, where low doses can greatly help cognitive measurements in disorders such as MDD179–185 and attention deficit hyperactivity disorder (ADHD),180–186 whereas much higher doses or different formulations of abuse can be detrimental cognitively or even cause psychosis in those predisposed.181–187”

    From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [181]

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Research works printed but not linked: 1

  1. [33]Spielberger CD Gorsuch RL Lushene R State-Trait Anxiety Inventory Test Manual for Form Y 1983 Consulting Psychological Press Palo Alto

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Authors
Price, R. B., Iosifescu, D. V., Murrough, J. W., Chang, L. C., Al Jurdi, R. K., Iqbal, S. Z., Soleimani, L., Charney, D. S., Foulkes, A. L., & Mathew, S. J.
Affiliations
  • University of Pittsburgh (US)
  • Icahn School of Medicine at Mount Sinai (US)
  • Baylor College of Medicine (US)
  • Mental Health Care Line; Michael E. Debakey VA Medical Center; Houston Texas
  • Michael E. DeBakey VA Medical Center (US)
Corresponding author
Mathew, Sanjay J.
ORCID
Venue
Depression and Anxiety
Publisher
Wiley
Published
2014-03-25
Volume
31
Issue
4
Pages
335-343
ISSN
1091-4269 (ISSN-L)
DOI
10.1002/da.22253
PMC
PMC4112410
OpenAlex
W1865092458
Cited by
345
References
45
Citations by year
2026: 13 · 2025: 14 · 2024: 17 · 2023: 24 · 2022: 33 · 2021: 32 · 2020: 36 · 2019: 30 · 2018: 44 · 2017: 25 · 2016: 29 · 2015: 37 · 2014: 11
FWCI
24.54
Type
journal article
Language
en
Open access
Licence
doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 525 d)
Locations
  • Depression and Anxiety (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • OSF Preprints (OSF Preprints) (submittedVersion)
Funders
  • U.S. Department of Veterans Affairs
  • Bristol-Myers Squibb
  • AstraZeneca
  • Sunovion
  • National Alliance for Research on Schizophrenia and Depression
  • BrainsWay
  • Servier
  • National Institutes of Health (UL1TR000067)
  • Genentech
  • Allergan
  • National Institute of Mental Health (RO1 MH, R01MH081870, K23MH094707, K23MH100259)
  • National Center for Advancing Translational Sciences (TR000067)
  • Janssen Pharmaceuticals
  • U.S. Army Medical Research Acquisition Activity
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
  • Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
Keywords
ketamine, suicidal cognitions, treatment-resistant depression, Implicit Association Test, midazolam, rapid-acting antidepressants, suicide risk, depressive symptoms
MeSH terms
Suicide Prevention, Adult, Analgesics, Cognition, Double-Blind Method, Female, Humans, Ketamine, Male, Midazolam, Middle Aged, Psychiatric Status Rating Scales, Suicide, Anti-Anxiety Agents, Suicidal Ideation, Depressive Disorder, Treatment-Resistant

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