Keilp John G, Madden Sean P, Marver Julia E, Frawley Abigail, Burke Ainsley K, Herzallah Mohammad M, Gluck Mark, Mann J John, Grunebaum Michael F
Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, New York.
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York.
J Clin Psychiatry. 2021 Nov 2;82(6):21m13921. doi: 10.4088/JCP.21m13921.
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. 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. 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. 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. ClinicalTrials.gov identifier: NCT01700829.
亚麻醉剂量的氯胺酮能迅速减轻一些抑郁症患者的抑郁症状和自杀观念。尽管某些神经认知缺陷与自杀行为有关，超出了临床症状范畴，但氯胺酮对有明显自杀观念的此类个体的神经认知功能的影响尚不清楚。在本研究中，有临床显著自杀观念的抑郁症患者（n = 78）在接受静脉注射氯胺酮（n = 39）或咪达唑仑（n = 39）双盲治疗前和治疗后1天接受了神经心理学测试。随机分配到咪达唑仑组且在初始输注后自杀观念未缓解的一个亚组接受了开放氯胺酮治疗，并在该治疗后一天接受了额外的神经认知测试。主要结局是该神经认知测试组合的表现变化。该研究于2012年11月至2017年1月进行。与咪达唑仑相比，盲法使用氯胺酮能使自杀观念和情绪迅速改善，正如我们之前所报道的。与咪达唑仑相比，氯胺酮还与反应时间（选择反应时）和干扰处理/认知控制（计算机化斯特鲁普任务）的特定改善有关——后者是一种与过去抑郁症患者自杀未遂相关的测量方法。在后来接受开放氯胺酮治疗并重新测试的咪达唑仑未缓解者中，反应时间和干扰处理/认知控制相对于他们之前的两次评估也有所改善。然而，神经认知改善与抑郁、自杀思维或总体情绪的变化无关。总体而言，在抑郁症背景下，发现氯胺酮在治疗后1天对至少1种与自杀行为相关的测量指标的神经认知有积极治疗作用。结果表明氯胺酮在治疗有自杀行为风险的抑郁症患者方面有额外的独立治疗效果。ClinicalTrials.gov标识符：NCT01700829。
