Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial
Abstract
Background.: Suicide is a devastating public health problem and very few biological treatments have been found to be effective for quickly reducing the intensity of suicidal ideation (SI). We have previously shown that a single dose of ketamine, a glutamate N -methyl- d -aspartate (NMDA) receptor antagonist, is associated with a rapid reduction in depressive symptom severity and SI in patients with treatment-resistant depression. Method.: We conducted a randomized, controlled trial of ketamine in patients with mood and anxiety spectrum disorders who presented with clinically significant SI ( n = 24). Patients received a single infusion of ketamine or midazolam (as an active placebo) in addition to standard of care. SI measured using the Beck Scale for Suicidal Ideation (BSI) 24 h post-treatment represented the primary outcome. Secondary outcomes included the Montgomery–Asberg Depression Rating Scale – Suicidal Ideation (MADRS-SI) score at 24 h and additional measures beyond the 24-h time-point. Results.: The intervention was well tolerated and no dropouts occurred during the primary 7-day assessment period. BSI score was not different between the treatment groups at 24 h ( p = 0.32); however, a significant difference emerged at 48 h ( p = 0.047). MADRS-SI score was lower in the ketamine group compared to midazolam group at 24 h ( p = 0.05). The treatment effect was no longer significant at the end of the 7-day assessment period. Conclusions.: The current findings provide initial support for the safety and tolerability of ketamine as an intervention for SI in patients who are at elevated risk for suicidal behavior. Larger, well-powered studies are warranted.
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Altered expression of NMDA, AMPA, and kainite glutamate receptors is linked to suicidal behavior and may play a role in the rapid-onset antidepressant and antisuicidal effects of ketamine.
“Altered expression of glutamate receptor N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and kainite glutamate receptors is linked to suicidal behavior (129) and may play a role in the rapid-onset antidepressant and antisuicidal effects of ketamine (130-135).”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [133]
The anti-suicidal ideation effect of ketamine is only partly explained by its antidepressant action, and effects on memory and cognition may also play a role.
“The anti–suicidal ideation effect of ketamine is only partly explained by its antidepressant action, and effects on memory and cognition may also play a role (131-133).”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [133]
Intravenous ketamine rapidly reduces depressive symptoms and suicidal ideation in hours instead of weeks.
“Intravenous ketamine is a rapidly acting treatment that robustly reduces depressive symptoms and suicidal ideation in hours instead of weeks (130-133).”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [133]
Ketamine's emergent use on suicidal ideation has short-lived effects for some suicidal patients.
“the emergent use of ketamine on suicidal ideation for a few days [14] has short-lived effects for some suicidal patients.”
From One Size Does Not Fit All: A Comprehensive Clinical Approach to Reducing Suicidal Ideation, Attempts, and Deaths (2019) · cites this paper as [14]
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- Authors
- Murrough, J. W., Soleimani, L., DeWilde, K. E., Collins, K. A., Lapidus, K. A., Iacoviello, B. M., Lener, M., Kautz, M., Kim, J., Stern, J. B., Price, R. B., Perez, A. M., Brallier, J. W., Rodriguez, G. J., Goodman, W. K., Iosifescu, D. V., & Charney, D. S.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Stony Brook University (US)
- University of California, Los Angeles (US)
- Drexel University (US)
- University of Pittsburgh (US)
- Corresponding author
- Murrough, J. W.
- ORCID
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2015-08-12
- Volume
- 45
- Issue
- 16
- Pages
- 3571-3580
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- OpenAlex
- W1885564923
- Cited by
- 297
- References
- 52
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 21 · 2023: 31 · 2022: 33 · 2021: 38 · 2020: 43 · 2019: 30 · 2018: 29 · 2017: 20 · 2016: 19 · 2015: 5
- FWCI
- 17.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Brain and Behavior Research Foundation
- Brain Research Foundation
- BrainsWay
- National Institutes of Health
- National Institute of Mental Health (K23MH104465)
- National Center for Advancing Translational Sciences
- 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 ideation, NMDA receptor antagonists, rapid-acting antidepressants, treatment-resistant depression, suicide risk, safety and tolerability
- MeSH terms
- Adult, Bipolar Disorder, Depression, Depressive Disorder, Major, Major Depressive Disorder, Double-Blind Method, Female, Humans, Ketamine, Male, Middle Aged, Psychiatric Status Rating Scales, Stress Disorders, Post-Traumatic, Treatment Outcome, Excitatory Amino Acid Antagonists, Suicidal Ideation
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