TY - JOUR
T1 - Effects of Ketamine Versus Midazolam on Neurocognition at 24 Hours in Depressed Patients With Suicidal Ideation
AU - Keilp, John G.
AU - Madden, Sean P.
AU - Marver, Julia E.
AU - Frawley, Abigail
AU - Burke, Ainsley K.
AU - Herzallah, Mohammad M.
AU - Gluck, Mark
AU - Mann, J. John
AU - Grunebaum, Michael F.
N1 - Funding Information:
Submitted: February 8, 2021; accepted June 7, 2021. Published online: November 2, 2021. Potential conflicts of interest: Dr Keilp and his spouse hold stock in Pfizer, Inc. and Zoetis, Inc. Drs Burke and Mann receive royalties for commercial use of the Columbia-Suicide Severity Rating Scale, which was not used in this study. The other authors report no other relevant funding or any potential conflicts of interest regarding this study. Funding/support: Supported by R01 MH096784 from the National Institute of Mental Health, Bethesda, MD. Role of the sponsor: The funding source approved the initial design of the study and monitored safety and progress of the clinical trial. It had no role in the management, analysis, or interpretation of the data. Acknowledgments: The authors thank the inpatient staff of the Clinical Research Unit at the New York State Psychiatric Institute for their support during this study. They also thank the individuals who participated in this study at a difficult point in their lives.
Publisher Copyright:
Copyright © 2021 Physicians Postgraduate Press, Inc.
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
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U2 - 10.4088/JCP.21M13921
DO - 10.4088/JCP.21M13921
M3 - Article
AN - SCOPUS:85121988375
VL - 82
JO - Diseases of the Nervous System
JF - Diseases of the Nervous System
SN - 0160-6689
IS - 6
M1 - 21M13921
ER -