Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada.
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
J Affect Disord. 2020 Nov 1;276:576-584. doi: 10.1016/j.jad.2020.06.050. Epub 2020 Jul 21.
Ketamine is established as a rapid and effective treatment in adults with treatment-resistant depression (TRD). The availability of different formulations and routes of delivery invites the need for evaluating relative effect sizes.
Effect size with respect to depression symptom reduction for each formulation and route of delivery was compared at discrete time-points (i.e., 24 h, 2-6 days, 7-20 days, 21-28 days) in adults with TRD. A random-effects meta-analysis was conducted to evaluate the effect size across intravenous, intranasal and oral routes of administration. Analysis was also conducted evaluating the effect size of racemic ketamine to esketamine.
The pooled effect size for intranasal ketamine/esketamine at 24 h was g = 1.247 (n = 5, 95% CI: 0.591-1.903, p < 0.01). At 2-6 days, the pooled effect size for intravenous ketamine/esketamine was g = 0.949 (n = 14, 95% CI: -0.308-2.206, p = 0.139). At 7-20 days, intranasal ketamine had a pooled effect size of g = 1.018 (n = 4, 95% CI: 0.499-1.538, p < 0.01). At 21-28 days, oral ketamine had a pooled effect size of g = 0.633 (n = 2, 95% CI: 0.368-0.898, p < 0.01).
Additional comparative studies are needed with regards to the efficacy of different formulations and routes of delivery.
The short-term efficacy of intravenous and intranasal ketamine/esketamine for adults with TRD was established. Interpreting the efficacy of oral ketamine was limited by the need for studies with larger samples across independent sites. No conclusions regarding comparative efficacy of the disparate formulations and routes of delivery can be derived from this analysis. Direct comparative studies are needed to further inform treatment options for TRD.
氯胺酮已被确立为治疗成人难治性抑郁症（TRD）的快速有效的治疗方法。不同配方和给药途径的可用性需要评估相对效果大小。
在 TRD 成人中，比较了每种配方和给药途径在离散时间点（即 24 小时、2-6 天、7-20 天、21-28 天）的抑郁症状减轻的效果大小。进行了随机效应荟萃分析，以评估静脉内、鼻内和口服给药途径的效果大小。还分析了外消旋氯胺酮到艾司氯胺酮的效果大小。
鼻内氯胺酮/艾司氯胺酮在 24 小时的汇总效应大小为 g=1.247（n=5，95%CI：0.591-1.903，p<0.01）。在 2-6 天，静脉内氯胺酮/艾司氯胺酮的汇总效应大小为 g=0.949（n=14，95%CI：-0.308-2.206，p=0.139）。在 7-20 天，鼻内氯胺酮的汇总效应大小为 g=1.018（n=4，95%CI：0.499-1.538，p<0.01）。在 21-28 天，口服氯胺酮的汇总效应大小为 g=0.633（n=2，95%CI：0.368-0.898，p<0.01）。
需要更多关于不同配方和给药途径疗效的比较研究。
确立了静脉内和鼻内氯胺酮/艾司氯胺酮治疗 TRD 成人的短期疗效。由于需要在独立站点进行更大样本量的研究，因此对口服氯胺酮的疗效进行解释受到限制。不能从该分析中得出关于不同配方和给药途径的相对疗效的结论。需要直接比较研究来进一步为 TRD 的治疗选择提供信息。
