Ketamine as a Potential Treatment for Suicidal Ideation: A Systematic Review of the Literature
Open accessAbstract
OBJECTIVE: To review the published literature on the efficacy of ketamine for the treatment of suicidal ideation (SI). METHODS: The PubMed and Cochrane databases were searched up to January 2015 for clinical trials and case reports describing therapeutic ketamine administration to patients presenting with SI/suicidality. Searches were also conducted for relevant background material regarding the pharmacological function of ketamine. RESULTS: Nine publications (six studies and three case reports) met the search criteria for assessing SI after administration of subanesthetic ketamine. There were no studies examining the effect on suicide attempts or death by suicide. Each study demonstrated a rapid and clinically significant reduction in SI, with results similar to previously described data on ketamine and treatment-resistant depression. A total of 137 patients with SI have been reported in the literature as receiving therapeutic ketamine. Seven studies delivered a dose of 0.5 mg/kg intravenously over 40 min, while one study administered a 0.2 mg/kg intravenous bolus and another study administered a liquid suspension. The earliest significant results were seen after 40 min, and the longest results were observed up to 10 days postinfusion. CONCLUSION: Consistent with clinical research on ketamine as a rapid and effective treatment for depression, ketamine has shown early preliminary evidence of a reduction in depressive symptoms, as well as reducing SI, with minimal short-term side effects. Additional studies are needed to further investigate its mechanism of action, long-term outcomes, and long-term adverse effects (including abuse) and benefits. In addition, ketamine could potentially be used as a prototype for further development of rapid-acting antisuicidal medication with a practical route of administration and the most favorable risk/benefit ratio.
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Clozapine remains relatively underutilized for the prevention of suicidal behaviour in patients with psychosis, probably because of the required laboratory monitoring given the risk of neutropenia and agranulocytosis.
“Nonetheless, clozapine remains relatively underutilized for the prevention of suicidal behaviour in patients with psychosis, probably because of the required laboratory monitoring given the risk of neutropenia and agranulocytosis in patients treated with this drug 306 .”
From Suicide and suicide risk (2019) · cites this paper as [306]
The Discussion (page not provided) says clozapine reduces suicide risk in patients with schizophrenia. It does not say clozapine is underutilized or attribute its use to laboratory monitoring or risks of neutropenia and agranulocytosis; searches for those terms found no supporting passage. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAltered 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 [130]
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 [130]
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References 48 · Cited by 120
- Authors
- Reinstatler, L., & Youssef, N. A.
- Affiliations
- Augusta University (US)
- Corresponding author
- Youssef, Nagy A.
- Venue
- Drugs in R&D
- Published
- 2015-02-10
- Volume
- 15
- Issue
- 1
- Pages
- 37-43
- ISSN
- 1174-5886 (ISSN-L)
- 1179-6901
- PMC
- PMC4359177
- OpenAlex
- W2126798879
- Cited by
- 120
- References
- 48
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 8 · 2023: 7 · 2022: 11 · 2021: 14 · 2020: 9 · 2019: 7 · 2018: 11 · 2017: 17 · 2016: 19 · 2015: 10 · 2012: 1
- FWCI
- 2.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Drugs in R&D (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- 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, suicide prevention, rapid-acting antidepressants, treatment-resistant depression, antidepressant efficacy, ketamine side effects, suicide attempts
- MeSH terms
- Suicide Prevention, Depression, Humans, Ketamine, Suicide, Time Factors, Excitatory Amino Acid Antagonists, Suicidal Ideation
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