Data Sheet 1_Comparative safety and tolerability of ketamine and esketamine for major depressive disorder: a systematic review and meta-analysis.pdf

BackgroundKetamine and esketamine have demonstrated rapid, short-term antidepressant effects in major depressive disorder (MDD), but their relative safety remains unclear. This review aims to update the evidence on the safety of two agents for MDD and indirectly compare their safety and tolerability.
MethodWe systematically searched PubMed, PsycINFO, Embase, and Cochrane databases up to 1 May 2025. Eligible studies compared ketamine or esketamine with placebo, active psychotropic agents, or electroconvulsive therapy in adults with MDD.
ResultsWe retrieved 5,473 articles, 47 of which met the inclusion criteria. For ketamine versus placebo, both dropout and incidence rates of adverse events (AEs) were statistically significant, with number needed to harm (NNH) values of 12 and 2, respectively. A similar pattern of effect sizes was found for esketamine, but with higher corresponding NNH values. Conversely, neither the meta-analysis nor NNH analyses of the incidence of serious AEs for ketamine and esketamine were statistically significant. A series of AEs like dizziness, dissociation, nausea, vertigo, and vision blurred, with relatively low NNH values, would be more likely to occur in clinical practice and exhibit dose-dependent effects. Moreover, ketamine or esketamine was associated with transient and significant psychiatric side-effects, blood pressure increases, and sedation post-dose. No significant abnormalities were observed in cognitive impairments, laboratory results, bladder symptoms, nasal examination, or addiction-related evaluations for either drug.
ConclusionAlthough further promising evidence supports the safety of ketamine and esketamine for MDD, the findings of this study highlight a potential tolerability advantage with esketamine over ketamine for short-term use for MDD. These findings require further validation through direct head-to-head clinical trials comparing these two drugs.
Systematic Review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42023389486.

背景 氯胺酮（ketamine）与艾司氯胺酮（esketamine）在重度抑郁症（major depressive disorder, MDD）中均展现出快速短期抗抑郁疗效，但二者的相对安全性仍未明确。
方法 本研究系统性检索了截至2025年5月1日的PubMed、PsycINFO、Embase及Cochrane数据库。纳入的研究需对比成人重度抑郁症患者使用氯胺酮、艾司氯胺酮与安慰剂、活性精神药物或电抽搐治疗的疗效与安全性。
结果 本研究共检索到5473篇文献，其中47篇符合纳入标准。相较于安慰剂，氯胺酮组的脱落率与不良事件（adverse events, AEs）发生率均具有统计学显著性，需伤害例数（number needed to harm, NNH）分别为12与2。艾司氯胺酮的效应量模式与之相似，但对应需伤害例数更高。反之，针对氯胺酮与艾司氯胺酮的严重不良事件发生率所开展的Meta分析及需伤害例数分析均未显示统计学显著性。头晕、解离症状、恶心、眩晕及视物模糊等一系列不良事件的需伤害例数相对较低，在临床实践中更易发生，且呈现剂量依赖性效应。此外，氯胺酮或艾司氯胺酮与给药后短暂且显著的精神科不良反应、血压升高及镇静作用相关。两种药物均未在认知功能损害、实验室检查结果、膀胱症状、鼻腔检查或成瘾相关评估中观察到显著异常。
结论 尽管已有更多有前景的证据支持氯胺酮与艾司氯胺酮用于重度抑郁症治疗的安全性，但本研究结果显示，在重度抑郁症短期治疗中，艾司氯胺酮的耐受性可能优于氯胺酮。该结论尚需通过直接头对头对比两种药物的临床试验进一步验证。
系统综述注册 本系统综述注册链接为https://www.crd.york.ac.uk/PROSPERO/view/CRD42023389486，注册号为CRD42023389486。