Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Canadian Rapid Treatment Centre of Excellence (CRTCE), Braxia Health, ON, Canada.
J Affect Disord. 2022 Dec 1;318:139-149. doi: 10.1016/j.jad.2022.08.050. Epub 2022 Aug 29.
Ketamine has demonstrated rapid and significant antidepressant effects in patients with treatment resistant depression (TRD). Herein, we conducted a systematic review to determine ketamine's efficacy as a function of the stage of treatment resistance (e.g., number of failed treatments) among individuals with TRD.
A systematic search of PubMed and Scopus from inception to August 2021 was conducted. Where applicable, the studies were categorized into low and high stages of resistance, where low category included studies where the mean number of failed antidepressants was <3 or had a higher proportion of subjects with ≤2 antidepressant trials. Reported indicators of treatment resistance and efficacy were extracted from randomized-controlled trials (RCTs) assessing ketamine or esketamine for TRD.
In total, 18 RCTs were included in the current review. There was variability across reported indicators of disease severity, definition of treatment resistance, as well as treatment protocols, preventing clear direct and indirect comparison of relative efficacy of ketamine at different stages of treatment resistance. Ketamine was effective in reducing depressive symptoms in RCTs at both lower and higher stages of treatment resistance; however, the effect size and duration of effects was greater in RCTs of lower stage of treatment resistance.
Our findings suggested that ketamine has antidepressant efficacy across all identified stages of treatment resistance, however with increasing failed treatment trials, treatment might be less efficacious. At this time, the comparative efficacy as a function of resistance stage remains to be well-established. Evaluation of participant level data is required to more clearly determine the association between level of treatment resistance and likelihood of response.
氯胺酮已在治疗抵抗性抑郁症（TRD）患者中显示出快速而显著的抗抑郁作用。在此，我们进行了一项系统评价，以确定氯胺酮在 TRD 患者中作为治疗抵抗程度的函数（例如，失败治疗的次数）的疗效。
从开始到 2021 年 8 月，对 PubMed 和 Scopus 进行了系统搜索。在适用的情况下，将研究分为低和高抵抗阶段，低类别包括平均失败抗抑郁药数<3 或有更高比例的受试者接受≤2 次抗抑郁试验的研究。从评估氯胺酮或依他佐辛治疗 TRD 的随机对照试验（RCT）中提取报告的治疗抵抗和疗效指标。
共有 18 项 RCT 纳入了本综述。报告的疾病严重程度指标、治疗抵抗的定义以及治疗方案存在差异，这使得无法清楚地直接和间接比较氯胺酮在不同治疗抵抗阶段的相对疗效。在 RCT 中，氯胺酮在低和高治疗抵抗阶段均能有效降低抑郁症状；然而，在低治疗抵抗阶段的 RCT 中，效果大小和效果持续时间更大。
我们的研究结果表明，氯胺酮在所有确定的治疗抵抗阶段都具有抗抑郁疗效，但随着失败治疗试验的增加，治疗效果可能会降低。此时，作为抵抗阶段的功能的比较疗效仍有待很好地确定。需要评估参与者水平的数据，以更清楚地确定治疗抵抗水平与反应可能性之间的关联。
