The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis
This systematic review (2018) and meta-analysis (n=176) examined the effects of ketamine on suicidal ideation using patient-level data from various studies that applied a single-dose intravenous administration route to treat any type of psychiatric disorder. Ketamine significantly reduced suicidal ideation for up to one week after the infusion.
Authors
- Sanjay Mathew
- Carlos Zarate
- Gerard Sanacora
Published
Abstract
Objective
Suicide is a public health crisis with limited treatment options. The authors conducted a systematic review and individual participant data meta-analysis examining the effects of a single dose of ketamine on suicidal ideation.
Method
Individual participant data were obtained from 10 of 11 identified comparison intervention studies that used either saline or midazolam as a control treatment. The analysis included only participants who had suicidal ideation at baseline (N=167). A one-stage, individual participant data, meta-analytic procedure was employed using a mixed-effects, multilevel, general linear model. The primary outcome measures were the suicide items from clinician-administered (the Montgomery-Åsberg Depression Rating Scale [MADRS] or the Hamilton Depression Rating Scale [HAM-D]) and self-report scales (the Quick Inventory of Depressive Symptomatology-Self Report [QIDS-SR] or the Beck Depression Inventory [BDI]), obtained for up to 1 week after ketamine administration.
Results
Ketamine rapidly (within 1 day) reduced suicidal ideation significantly on both the clinician-administered and self-report outcome measures. Effect sizes were moderate to large (Cohen’s d=0.48-0.85) at all time points after dosing. A sensitivity analysis demonstrated that compared with control treatments, ketamine had significant benefits on the individual suicide items of the MADRS, the HAM-D, and the QIDS-SR but not the BDI. Ketamine’s effect on suicidal ideation remained significant after adjusting for concurrent changes in severity of depressive symptoms.
Conclusions
Ketamine rapidly reduced suicidal thoughts, within 1 day and for up to 1 week in depressed patients with suicidal ideation. Ketamine’s effects on suicidal ideation were partially independent of its effects on mood, although subsequent trials in transdiagnostic samples are required to confirm that ketamine exerts a specific effect on suicidal ideation. Additional research on ketamine’s long-term safety and its efficacy in reducing suicide risk is needed before clinical implementation.
Research Summary of 'The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis'
Introduction
Suicide is a major public health problem and rates have risen despite available treatments. Earlier research has shown that subanesthetic doses of ketamine produce rapid antidepressant effects and there is preliminary evidence that ketamine may reduce suicidal thoughts, but no meta-analysis had specifically examined ketamine's effects on suicidal ideation at the individual participant level across single-dose, controlled intravenous trials. Wilkinson and colleagues conducted a systematic review and individual participant data (IPD) meta-analysis to determine whether a single intravenous ketamine infusion reduces suicidal ideation more rapidly than control treatments (saline or midazolam) in patients who had some suicidal ideation at baseline. The analysis focused on explicit suicide-item scores from clinician-administered and self-report depression scales up to 1 week after infusion, and sought to examine whether any antisuicidal effect was independent of change in overall depressive symptom severity.
Expert Research Summaries
Go Pro to access AI-powered section-by-section summaries, editorial takes, and the full research toolkit.
Full Text PDF
Full Paper PDF
Create a free account to open full-text PDFs.
Study Details
- Study Typemeta
- Journal
- Compound
- Topics
- Authors
- APA Citation
Wilkinson, S. T., Ballard, E. D., Bloch, M. H., Mathew, S. J., Murrough, J. W., Feder, A., Sos, P., Wang, G., Zarate, C. A., & Sanacora, G. (2018). The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis. American Journal of Psychiatry, 175(2), 150-158. https://doi.org/10.1176/appi.ajp.2017.17040472
References (7)
Papers cited by this study that are also in Blossom
Berman, R. M., Cappiello, A., Anand, A. et al. · Biological Psychiatry (2000)
Zarate, C. A., Brutsche, N. E., Ibrahim, L. et al. · Biological Psychiatry (2012)
Diazgranados, N., Ibrahim, L., Brutsche, N. E. et al. · JAMA Psychiatry (2010)
Murrough, J. W., Iosifescu, D. V., Chang, L. C. et al. · American Journal of Psychiatry (2013)
Ionescu, D. F., Vande Voort, J. L., Niciu, M. J. et al. · Journal of Psychiatric Research (2014)
Sos, P., Klirova, M., Novák, T. et al. · Neuropsychiatric Disease And Treatment (2013)
Sanacora, G., Frye, M. A., McDonald, W. et al. · JAMA Psychiatry (2017)
Cited By (45)
Papers in Blossom that reference this study
Schlegelmilch, M., Plint, A. C., Barrowman, N. et al. · BMC Psychiatry (2026)
Mallevays, M., Fuet, L., Danon, M. et al. · MedRvix (2026)
Ballard, E. D., Greenstein, D., Reiss, P. T. et al. · Translational Psychiatry (2024)
Zhou, Y., Lan, X-F., Wang, C. et al. · Child and Adolescent Psychiatry (2024)
O'Brien, B., Lee, J., Kim, S. et al. · Psychiatry Research (2024)
La Torre, J. T., Mahammadli, M., Faber, S. et al. · International Journal of Mental Health and Addiction (2023)
Lan, X-F., Wang, C-Y., Zhang, F. et al. · Child and Adolescent Psychiatry (2023)
Hietamies, T. M., Mcinnes, L. A., Klise, A. J. et al. · Journal of Affective Disorders (2023)
Chisamore, N., Danayan, K., Rodrigues, N. B. et al. · Journal of Psychopharmacology (2023)
Wang, C., Lan, X-F., Zhou, Y. · Frontiers in Neuroscience (2023)
Show all 45 papersShow fewer
Lapidos, A., Lopez-Vives, D., Sera, C. E. et al. · Journal of Affective Disorders (2023)
Zhang, J. C., Yao, W., Hashimoto, K. · Neuropharmacology (2022)
Surjan, J., Grossi, J. D., Del Porto, J. A. et al. · Clinical Drug Investigation (2022)
Shamabadi, A., Ahmadzade, A., Hasanzadeh, A. · British Journal of Clinical Pharmacology (2022)
Gerner, J., Bloomfield-Clagett, B., Zarate, C. A. · Journal of Affective Disorders (2022)
Ragnhildstveit, A., Slayton, M., Jackson, L. K. et al. · Brain Sciences (2022)
La Torre, J. T., Mahammadli, M., Greenway, K. T. et al. · BMC Psychiatry (2022)
Nikkheslat, N. · Brain Behavior and Immunity - Health (2021)
Zhou, Y-L., Wang, C., Lan, X-F. et al. · Journal of Psychiatric Research (2021)
Wilkowska, A., Wiglusz, M. S., Cubała, W. J. et al. · Frontiers in Psychiatry (2021)
Kopra, E., Mondelli, V., Pariante, C. et al. · Journal of Psychopharmacology (2021)
Bird, C. I. V., Modlin, N. L., Rucker, J. · International Review of Psychiatry (2021)
Feeney, A., Hock, R. S., Freeman, M. P. et al. · European Neuropsychopharmacology (2021)
Siegel, A. N., Di, J. D., Brietzke, E. et al. · Journal of Psychiatric Research (2021)
Bahji, A., Zarate, C. A., Vazquez, G. H. · International Journal of Neuropsychopharmacology (2021)
Ross, E., Agin-Liebes, G. I., Zeifman, R. J. et al. · ACS Pharmacology and Translational Science (2021)
Mcintyre, R. S., Rosenblat, J. D., Nemeroff, C. B. et al. · American Journal of Psychiatry (2021)
Ballard, E. D., Fields, J., Farmer, C. A. et al. · Suicide and Life-Threatening Behavior (2021)
Domany, Y., McCullumsmith, C. B. · Archives of Suicide Research (2021)
Bahji, A., Vazquez, G. H., Zarate, C. A. · Journal of Affective Disorders (2021)
Alipoor, M., Loripoor, M., Kazemi, M. et al. · Journal of Medicine and Life (2021)
Lascelles, K., Marzano, L., Brand, F. et al. · BJPsych Open (2020)
Wilkowska, A., Szałach, L., Cubała, W. J. · Neuropsychiatric Disease And Treatment (2020)
Jelen, L. A., Young, A. H., Stone, J. M. · Journal of Psychopharmacology (2020)
Basso, L., Bönke, L., Aust, S. et al. · Journal of Psychiatric Research (2020)
Krediet, E., Bostoen, T., Breeksema, J. J. et al. · International Journal of Neuropsychopharmacology (2020)
Araújo, D. B., Zeifman, R. J., Palhano-Fontes, F. et al. · Frontiers in Pharmacology (2019)
Hashimoto, K. · Psychiatry and Clinical Neurosciences (2019)
Williams, N. R., Heifets, B. D., Bentzley, B. S. et al. · Molecular Psychiatry (2019)
Zheng, W., Zhou, Y-L., Wang, C-Y. · Journal of Psychopharmacology (2019)
Zheng, W., Zhou, Y-L., Liu, W. et al. · Journal of Psychiatric Research (2018)
Abdallah, C. G., Sanacora, G., Duman, R. S. et al. · Chronic Stress (2018)
Thomas, R. K., Baker, G., Lind, J. et al. · Journal of Psychopharmacology (2018)
Rong, C., Park, C., Rosenblat, J. D. et al. · International Journal of Environmental Research and Public Health (2018)
Zanos, P., Thompson, S. M., Duman, R. S. et al. · CNS Drugs (2018)
Your Personal Research Library
Go Pro to save papers, add notes, rate studies, and organize your research into custom shelves.