From the Department of Psychiatry and the Child Study Center, Yale School of Medicine, New Haven, Conn.; the Experimental Therapeutics and Pathophysiology Branch, NIMH, Bethesda, Md.; the Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston; the Michael E. Debakey VA Medical Center, Houston; the Mood and Anxiety Disorders Program, Icahn School of Medicine at Mount Sinai, New York; the Department of Psychiatry, First Faculty of Medicine, Charles University, Prague, Czech Republic; and the Beijing Anding Hospital, Capital University of Medical Sciences, Beijing.
Am J Psychiatry. 2018 Feb 1;175(2):150-158. doi: 10.1176/appi.ajp.2017.17040472. Epub 2017 Oct 3.
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.
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.
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.
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.
自杀是一种公共卫生危机，治疗选择有限。作者进行了一项系统评价和个体参与者数据荟萃分析，考察了单次氯胺酮剂量对自杀意念的影响。
从 11 项已确定的对照干预研究中获得了个体参与者数据，这些研究使用生理盐水或咪达唑仑作为对照治疗。分析仅包括基线时有自杀意念的参与者（N=167）。采用一阶、个体参与者数据、荟萃分析程序，使用混合效应、多层次、广义线性模型。主要结局指标是氯胺酮给药后最多 1 周内由临床医生评估（蒙哥马利-阿斯伯格抑郁评定量表[MADRS]或汉密尔顿抑郁评定量表[HAM-D]）和自我报告量表（快速抑郁症状清单自评量表[QIDS-SR]或贝克抑郁量表[BDI]）获得的自杀项目。
氯胺酮在给药后 1 天内迅速显著降低自杀意念，在临床医生评估和自我报告的结局测量上均如此。效应大小为中等到较大（Cohen's d=0.48-0.85），在给药后所有时间点均如此。敏感性分析表明，与对照治疗相比，氯胺酮在 MADRS、HAM-D 和 QIDS-SR 的自杀项目上具有显著的获益，但在 BDI 上没有获益。在调整抑郁严重程度的同时变化后，氯胺酮对自杀意念的影响仍然显著。
氯胺酮可迅速降低有自杀意念的抑郁患者的自杀念头，在 1 天内，最长可达 1 周。氯胺酮对自杀意念的影响部分独立于其对情绪的影响，尽管需要在跨诊断样本中进行后续试验来确认氯胺酮对自杀意念有特定的影响。在临床实施之前，需要进一步研究氯胺酮的长期安全性及其降低自杀风险的疗效。
