Effects of Ketamine Versus Midazolam on Neurocognition at 24 Hours in Depressed Patients With Suicidal Ideation
This double-blind, parallel-group trial (n=78) compared the effects of intravenous ketamine versus midazolam on neurocognition in depressed patients with significant suicidal ideation. While ketamine rapidly reduced suicidal ideation and improved reaction time and cognitive control, these neurocognitive improvements were independent of changes in depression or mood.
Authors
- Michael Grunebaum
Published
Abstract
Objective
Subanesthetic ketamine rapidly reduces depressive symptoms and suicidal ideation in some depressed patients. Its effects on neurocognitive functioning in such individuals with significant suicidal ideation is not well understood, even though certain neurocognitive deficits are associated with suicide behavior beyond clinical symptoms.
Methods
In this study, depressed patients with clinically significant suicidal ideation (n = 78) underwent neuropsychological testing before and 1 day after double-blind treatment with intravenous ketamine (n = 39) or midazolam (n = 39). A subgroup randomized to midazolam whose ideation did not remit after initial infusion received open ketamine and additional neurocognitive testing a day after this treatment. The primary outcome was change in performance on this neurocognitive battery. The study was conducted between November 2012 and January 2017.
Results
Blinded ketamine produced rapid improvement in suicidal ideation and mood in comparison to midazolam, as we had reported previously. Ketamine, relative to midazolam, was also associated with specific improvement in reaction time (Choice RT) and interference processing/cognitive control (computerized Stroop task)-the latter a measure that has been associated with past suicide attempt in depression. In midazolam nonremitters later treated with open ketamine and retested, reaction time and interference processing/cognitive control also improved relative to both of their prior assessments. Neurocognitive improvement, however, was not correlated with changes in depression, suicidal thinking, or general mood.
Conclusions
Overall, ketamine was found to have a positive therapeutic effect on neurocognition 1 day after treatment on at least 1 measure associated with suicidal behavior in the context of depression. Results suggest additional independent therapeutic effects for ketamine in the treatment of depressed patients at risk for suicidal behavior.
Research Summary of 'Effects of Ketamine Versus Midazolam on Neurocognition at 24 Hours in Depressed Patients With Suicidal Ideation'
Introduction
Keilp and colleagues situate the study in the context of evidence that subanesthetic ketamine produces rapid antidepressant and antisuicidal effects within hours to days in some patients. They note a gap in knowledge about ketamine's effects on neurocognitive functions in depressed patients with clinically significant suicidal ideation, despite prior findings linking certain cognitive deficits (for example, slowed processing, impairments in cognitive control) to suicidal behaviour. Previous work in healthy volunteers has shown short‑term detrimental cognitive effects of ketamine across attention, memory, working memory and executive function that are dose dependent and tend to resolve within days; by contrast, some studies in depressed samples have reported cognitive improvements in the days after infusion, but results have been mixed and understudied in suicidal patients. This randomised, double‑blind trial therefore aimed to measure changes in neurocognitive performance from baseline to 24 hours after a single intravenous infusion of ketamine versus an active comparator, midazolam, in depressed inpatients with clinically significant suicidal ideation. The investigators hypothesised global neurocognitive improvement in the period corresponding to ketamine's clinical effects, and they also planned to examine whether baseline cognitive slowing predicted clinical response and whether changes in cognition correlated with changes in depression, suicidal thinking, or general mood. A secondary objective examined a subgroup of midazolam nonremitters who later received open‑label ketamine to determine whether cognitive effects seen after blinded ketamine would be reproduced after open treatment.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Author
- APA Citation
Keilp, J. G., Madden, S. P., Marver, J. E., Frawley, A., Burke, A. K., Herzallah, M. M., Gluck, M., Mann, J. J., & Grunebaum, M. F. (2021). Effects of Ketamine Versus Midazolam on Neurocognition at 24 Hours in Depressed Patients With Suicidal Ideation. The Journal of Clinical Psychiatry, 82(6). https://doi.org/10.4088/jcp.21m13921
References (1)
Papers cited by this study that are also in Blossom
Grunebaum, M. F., Galfalvy, H. C., Choo, T. H. et al. · American Journal of Psychiatry (2018)
Cited By (2)
Papers in Blossom that reference this study
Zavaliangos-Petropulu, A., Mcclintock, S. M., Khalil, J. et al. · Journal of Affective Disorders (2023)
Shiroma, P. R., Velit-Salazar, M. R., Vorobyov, Y. · Clinical Drug Investigation (2022)
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