Clinical trials for rapid changes in suicidal ideation: lessons from ketamine
Open accessAbstract
Rapid‐acting treatments for suicidal thoughts are critically needed. Consequently, there is a burgeoning literature exploring psychotherapeutic, pharmacologic, or device‐based brief interventions for suicidal thoughts characterized by a rapid onset of action. Not only do these innovative treatments have potentially important clinical benefits to patient populations, they also highlight a number of methodological considerations for suicide research. First, while most clinical trials related to suicide risk focus on suicide attempts, new clinical trials that use suicidal thoughts as the primary outcome require a number of slight modifications to their clinical trial design. Second, the rapid onset of these new interventions permits an experimental therapeutics approach to suicide research, in which psychological and neurobiological markers are embedded into clinical trials to better understand the underlying pathophysiology of suicidal thoughts. The following review discusses these methodological innovations in light of recent research using the N‐methyl‐D‐aspartate (NMDA) receptor antagonist ketamine, which has been associated with rapid effects on suicidal thoughts. We hope that “lessons learned” from the ketamine literature will provide a blueprint for all researchers evaluating rapid‐acting treatments for suicidal thoughts, whether pharmacologic or psychotherapeutic.
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Such an approach has the potential to further our understanding of both mechanisms of action for suicide-focused treatments as well as elucidate the neural correlates of suicide risk.
“Such an approach, which has already been implemented in rapid-acting clinical trials for depression (18), has the potential to further our understanding of both mechanisms of action for suicide-focused treatments as well as elucidate the neural correlates of suicide risk (19).”
From New methods for assessing rapid changes in suicide risk (2021) · cites this paper as [19]
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Suicide and Suicide Risk in Adolescents
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New methods for assessing rapid changes in suicide risk
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“Ketamine has also been investigated for its rapid effects on reducing suicidal thoughts independent of its antidepressant effect [6–9].”
- Authors
- Ballard, E. D., Fields, J., Farmer, C. A., & Zarate, C. A.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Ballard, Elizabeth D.
- Venue
- Suicide and Life-Threatening Behavior
- Publisher
- Wiley
- Published
- 2021-02
- Volume
- 51
- Issue
- 1
- Pages
- 27-35
- ISSN
- 0363-0234 (ISSN-L)
- 1943-278X
- PMC
- PMC8201419
- OpenAlex
- W3132180119
- Cited by
- 10
- References
- 64
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 2
- FWCI
- 1.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Suicide and Life-Threatening Behavior (publishedVersion, public-domain)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (IRP‐NIMH‐NIH, ZIAMH002857)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- suicidal ideation, ketamine, NMDA receptor antagonists, clinical trial design, suicide risk, experimental therapeutics, neurobiological markers, psychotherapeutic interventions, pharmacological interventions
- MeSH terms
- Clinical Trials as Topic, Depression, Humans, Ketamine, Suicide, Attempted, Biomarkers, Suicidal Ideation
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