{"title":"Clinical trials since 2020 of rapid anti-suicidal ideation effects of ketamine and its enantiomers: a systematic review.","authors":"Sumra Sajid, J John Mann, Michael F Grunebaum","doi":"10.1038/s41398-025-03255-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Suicide is a global public health problem with few empirically supported treatments.</p><p><strong>Methods: </strong>We conducted a systematic review of clinical trials (CT) since 2020 of racemic ketamine or one of its enantiomers' (R/S) potential to reduce suicidal ideation or behavior (SIB). An initial PubMed search on April 15th, 2024 yielded 2483 results. 104 relevant CTs were identified. An additional search using other search engines on March 19th, 2024 yielded 52 sources. After screening, 14 RCTs met the inclusion criteria which required clinically significant SIB among participants, ketamine or one of its enantiomers as an anti-SIB treatment, and SIB as an outcome. We excluded neuroimaging studies, meta-analyses, reviews, and case reports. Open-label studies were also excluded except in the case of R-ketamine where we included 2 open trials due to limited published data for this enantiomer, yielding a total of 16 CTs. We used the Revised Cochrane risk-of-bias tool for the RCTs. CTs reviewed had suicidal ideation (SI) but none had suicidal behavior as an outcome.</p><p><strong>Results: </strong>The studies include ketamine augmentation of other treatments such as electroconvulsive therapy (ECT), various routes of administration - intravenous (IV), intramuscular (IM), and intranasal (IN) - and single versus multiple dose designs. Multiple doses of IV ketamine/S-ketamine produced reductions in SI for periods of several days to weeks, while single doses showed shorter, more variable effects. Multiple and single doses of IN ketamine/S-ketamine and single doses of IV ketamine produced less consistent anti-SI results. IN and IV ketamine/S-ketamine administration appears to be well tolerated. R-ketamine appears to produce fewer side effects, but additional clinical research is needed to clarify its antidepressant and anti-SI effects in humans.</p><p><strong>Conclusion: </strong>This review affirms the time-limited, anti-SI effects of ketamine and the need for personalized treatment. Limitations include study heterogeneity, small samples, and paucity of data for suicidal behavior or R-ketamine.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"44"},"PeriodicalIF":6.2000,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802767/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41398-025-03255-0","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
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Abstract
Background: Suicide is a global public health problem with few empirically supported treatments.
Methods: We conducted a systematic review of clinical trials (CT) since 2020 of racemic ketamine or one of its enantiomers' (R/S) potential to reduce suicidal ideation or behavior (SIB). An initial PubMed search on April 15th, 2024 yielded 2483 results. 104 relevant CTs were identified. An additional search using other search engines on March 19th, 2024 yielded 52 sources. After screening, 14 RCTs met the inclusion criteria which required clinically significant SIB among participants, ketamine or one of its enantiomers as an anti-SIB treatment, and SIB as an outcome. We excluded neuroimaging studies, meta-analyses, reviews, and case reports. Open-label studies were also excluded except in the case of R-ketamine where we included 2 open trials due to limited published data for this enantiomer, yielding a total of 16 CTs. We used the Revised Cochrane risk-of-bias tool for the RCTs. CTs reviewed had suicidal ideation (SI) but none had suicidal behavior as an outcome.
Results: The studies include ketamine augmentation of other treatments such as electroconvulsive therapy (ECT), various routes of administration - intravenous (IV), intramuscular (IM), and intranasal (IN) - and single versus multiple dose designs. Multiple doses of IV ketamine/S-ketamine produced reductions in SI for periods of several days to weeks, while single doses showed shorter, more variable effects. Multiple and single doses of IN ketamine/S-ketamine and single doses of IV ketamine produced less consistent anti-SI results. IN and IV ketamine/S-ketamine administration appears to be well tolerated. R-ketamine appears to produce fewer side effects, but additional clinical research is needed to clarify its antidepressant and anti-SI effects in humans.
Conclusion: This review affirms the time-limited, anti-SI effects of ketamine and the need for personalized treatment. Limitations include study heterogeneity, small samples, and paucity of data for suicidal behavior or R-ketamine.
背景：自杀是一个全球性的公共卫生问题，很少有经验支持的治疗方法。方法：我们对自2020年以来有关消旋氯胺酮或其对映异构体之一（R/S）降低自杀意念或行为（SIB）潜力的临床试验（CT）进行了系统回顾。2024年4月15日，PubMed首次搜索产生了2483个结果。共鉴定出104例相关ct。在2024年3月19日使用其他搜索引擎进行额外搜索，得到52个来源。筛选后，14项rct符合纳入标准，即参与者中有临床显著的SIB，氯胺酮或其对映异构体之一作为抗SIB治疗，以及SIB作为结局。我们排除了神经影像学研究、荟萃分析、综述和病例报告。开放标签研究也被排除，但r -氯胺酮的研究除外，由于r -氯胺酮对映体已发表的数据有限，我们纳入了2项开放试验，总共有16项ct。我们使用修订Cochrane风险偏倚工具进行随机对照试验。ct检查有自杀意念（SI），但没有自杀行为作为结果。结果：研究包括氯胺酮增加其他治疗方法，如电休克治疗（ECT），各种给药途径-静脉注射（IV），肌肉注射（IM）和鼻内(IN) -以及单剂量与多剂量设计。多次剂量的静脉注射氯胺酮/ s -氯胺酮可使SI降低数天至数周，而单次剂量的效果较短，变化更大。多次和单次给药氯胺酮/ s -氯胺酮和单次给药氯胺酮的抗si效果不太一致。静脉注射氯胺酮/ s -氯胺酮耐受性良好。r -氯胺酮似乎产生较少的副作用，但需要更多的临床研究来阐明其对人类的抗抑郁和抗si作用。结论：本综述肯定了氯胺酮的时效性、抗si作用和个性化治疗的必要性。局限性包括研究的异质性、小样本和缺乏自杀行为或r -氯胺酮的数据。
期刊介绍：
Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.
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