Effects of Intravenous Ketamine on Explicit and Implicit Measures of Suicidality in Treatment-Resistant Depression
Open accessAbstract
Background Intravenous ketamine has shown rapid antidepressant effects in early trials, making it a potentially attractive candidate for depressed patients at imminent risk of suicide. The Implicit Association Test (IAT), a performance-based measure of association between concepts, may have utility in suicide assessment.Methods Twenty-six patients with treatment-resistant depression were assessed using the suicidality item of the Montgomery-Asberg Depression Rating Scale (MADRS-SI) 2 hours before and 24 hours following a single subanesthetic dose of intravenous ketamine. Ten patients also completed IATs assessing implicit suicidal associations at comparable time points. In a second study, nine patients received thrice-weekly ketamine infusions over a 12-day period.Results Twenty-four hours after a single infusion, MADRS-SI scores were reduced on average by 2.08 points on a 0 to 6 scale (p < .001; d = 1.37), and 81% of patients received a rating of 0 or 1 postinfusion. Implicit suicidal associations were also reduced following ketamine (p = .003; d = 1.36), with reductions correlated across implicit and explicit measures. MADRS-SI reductions were sustained for 12 days by repeated-dose ketamine (p < .001; d = 2.42).Conclusions These preliminary findings support the premise that ketamine has rapid beneficial effects on suicidal cognition and warrants further study.
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A single low-dose ketamine treatment elicits sustained antidepressant effects lasting more than 1 week in patients.
“Ketamine's half-life in the body is ;2 h (Autry et al., 2011), yet a single low-dose treatment elicits sustained (.1 week) antidepressant effects in patients (Berman et al., 2000;Zarate et al., 2006;Price et al., 2009), strongly suggesting it induces neuroplasticity (Duman, 2018).”
From Psychedelics and Neural Plasticity: Therapeutic Implications (2022) · cites this paper as Price et al., 2009
The Introduction reports reduced depressive symptoms 24 hours after a single subanesthetic ketamine dose. The Methods and Results (page numbers unavailable) show that the 12-day improvement was in suicidal-ideation scores among patients who received additional infusions, not antidepressant effects lasting more than a week after one treatment. (LLM, conf=0.88)
Experimental — accuracy not yet measuredKetamine 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 [135]
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 [57]
Ketamine has potent antidepressant effects, especially in treatment-resistant depressed patients.
“Administration of glutamate receptor antagonists, such as the NMDA antagonist, ketamine, have potent antidepressant effects especially in treatment resistant depressed patients”
From Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications (2013) · cites this paper as Price et al., 2009
Ketamine reduces suicide ideation.
“Recent studies report that ketamine also reduces suicide ideation, a major advance over typical antidepressants with low efficacy and delayed onset of action151,152.”
From Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants (2016) · cites this paper as [152]
Ketamine induces rapid amelioration of suicidal ideation in major depressed patients.
“Ketamine has been also shown to induce a rapid amelioration of suicidal ideation in major depressed patients 23, 24”
From Mechanisms of ketamine action as an antidepressant (2018) · cites this paper as [23]
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- Authors
- Price, R. B., Nock, M. K., Charney, D. S., & Mathew, S. J.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- Harvard University (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Price, Rebecca B.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 66
- Issue
- 5
- Pages
- 522-526
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC2935847
- OpenAlex
- W2118815581
- Cited by
- 600
- References
- 22
- Citations by year
- 2026: 15 · 2025: 16 · 2024: 18 · 2023: 25 · 2022: 43 · 2021: 49 · 2020: 43 · 2019: 39 · 2018: 31 · 2017: 34 · 2016: 46 · 2015: 62 · 2014: 45 · 2013: 42 · 2012: 43
- FWCI
- 21.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (F31 MH081468, K23-MH-069656, MO1-RR-00071)
- National Alliance for Research on Schizophrenia and Depression
- 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
- intravenous ketamine, treatment-resistant depression, suicidality, suicide risk, Implicit Association Test, rapid antidepressant effects, suicide assessment
- MeSH terms
- Suicide Prevention, Depression, Drug Resistance, Female, Humans, Infusions, Intravenous, Ketamine, Male, Middle Aged, Psychiatric Status Rating Scales, Suicide, Cohort Studies, Excitatory Amino Acid Antagonists
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