Single and repeated ketamine infusions for reduction of suicidal ideation in treatment-resistant depression
Open accessAbstract
Repeated administration of subanesthetic intravenous ketamine may prolong the rapid decrease in suicidal ideation (SI) elicited by single infusions. The purpose of this secondary analysis was to evaluate reduction in SI with a single ketamine infusion compared with an active control, and prolonged suppression of SI with repeated and maintenance infusions. Thirty-seven participants with treatment-resistant depression (TRD) and baseline SI first received a single ketamine infusion during a randomized, double-blind crossover with midazolam. Following relapse of depressive symptoms, participants received six open-label ketamine infusions administered thrice-weekly over 2 weeks. Antidepressant responders (≥50% decrease in Montgomery-Åsberg Depression Rating Scale [MADRS] scores) received four further open-label infusions administered once-weekly. Changes in SI were assessed with the suicide items on the MADRS (item 10, MADRS-SI) and the Quick Inventory of Depressive Symptomatology-Self Report (item 12, QIDS-SI). Linear mixed models revealed that compared with midazolam, a single ketamine infusion elicited larger reduction in SI (P = 0.01), with maximal effects measured at 7 days postinfusion (P < 0.001, Cohen's d = 0.83). Participants had cumulative reductions in MADRS-SI scores with repeated infusions (P < 0.001), and no further change with maintenance infusions (P = 0.94). QIDS-SI results were consistent with MADRS-SI. Overall, 69% of participants had a complete alleviation of SI following repeated infusions. In TRD, single and repeated ketamine infusions resulted in decreases in SI which were maintained with once-weekly maintenance infusions. This study adds to the growing body of research suggesting ketamine as a possible novel treatment strategy for SI in mood disorders.
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A double-blind crossover trial (n=37) found that 69% of participants had complete remission of suicidal ideation after six ketamine infusions, and this effect was maintained with weekly maintenance infusions.
“One double-blind, crossover trial (n = 37) found that 69% of participants had complete remission of suicidal ideation after six ketamine infusions, an effect maintained with weekly maintenance infusions [83].”
From Ketamine in neuropsychiatric disorders: an update (2024) · cites this paper as [83]
The Abstract and ‘Maintenance ketamine infusions’ section report 37 participants and that 24 participants (69%) had no suicidal ideation after six repeated infusions. However, the double-blind crossover applied only to the initial single-infusion phase; the six-infusion and weekly maintenance phases were open-label. The Discussion says weekly infusions sustained reductions in suicidal ideation among responders, not that the 69% complete-alleviation rate was maintained. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSeveral RCTs have looked at repeated infusions of six intravenous infusions over several weeks, but no long-term RCTs exist.
“Several RCTs have now looked at repeated infusions of six intravenous infusions over several weeks,60–62 but to date no long-term RCTs exist.”
From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [60]
One study of treatment resistant depression suggests that repeated doses of ketamine might be necessary for some patients to achieve remission of severe suicidal ideas.
“Additionally, one study of treatment resistant depression suggests that repeated doses of ketamine might be necessary for some patients to achieve remission of severe suicidal ideas.30”
From Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial (2022) · cites this paper as [30]
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- Authors
- Phillips, J. L., Norris, S., Talbot, J., Hatchard, T., Ortiz, A., Birmingham, M., Owoeye, O., Batten, L. A., & Blier, P.
- Affiliations
- University of Ottawa (CA)
- Institute of Mental Health Research (CA)
- Corresponding author
- Phillips, Jennifer L.
- Venue
- Neuropsychopharmacology
- Published
- 2019-11-23
- Volume
- 45
- Issue
- 4
- Pages
- 606-612
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC7021716
- OpenAlex
- W2990600117
- Cited by
- 139
- References
- 41
- Citations by year
- 2026: 18 · 2025: 13 · 2024: 27 · 2023: 22 · 2022: 22 · 2021: 26 · 2020: 11
- FWCI
- 9.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Gouvernement du Canada | Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Keywords
- ketamine, suicidal ideation, treatment-resistant depression, rapid-acting antidepressants, suicide prevention, mood disorders
- MeSH terms
- Adult, Anesthetics, Dissociative, Double-Blind Method, Drug Administration Schedule, Female, Humans, Infusions, Intravenous, Ketamine, Male, Middle Aged, Suicidal Ideation, Depressive Disorder, Treatment-Resistant
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