Nuñez, MD, MS, Pahwa, MD, Seshadri, MD, Kung, MD, Schak, MD, VandeVoort, MD, Frye, MD,Singh MD, MS, Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, USA. Joseph, MBBS, Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, USA, Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA. Prokop, MLS, Mayo Medical Libraries, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Psychopharmacol Bull. 2020 Sep 14;50(4):137-163.
Intravenous Ketamine has shown robust antidepressant efficacy although other routes of administration are currently needed. We conducted a systematic review and meta-analysis of studies evaluating the efficacy and tolerability of oral ketamine for depression.
A comprehensive search of major electronic databases from inception to April 2020 was performed. Studies of oral ketamine for depression, from case series to randomized clinical trials, were eligible. Randomized controlled trials were included in a meta-analysis, focusing on response, remission, time to effect, and side effects.
A total of 917 articles were identified with 890 studies screened, yielding a total of 10 studies included in our systematic review.Three randomized controlled trials (RCTs) (N = 161, mean age 37.9 ± 9.5 years, 58.6% females) were included in the meta-analysis. Pooled analysis suggested a significant antidepressant effect of oral ketamine (SMD: -0.75; 95% CI: -1.08, -0.43; p<0.0001; I = 0%) although remission rates (RR:2.77; 95% CI:0.96, 8.00; p = 0.06) and response rates (RR:2.58; 95% CI:0.94,7.08; p = 0.07) were marginal compared to placebo at the endpoint. Oral ketamine antidepressant effects seemed to take effect at the 2nd week (SMD: -0.71; 95% CI: -1.08, -0.35; p = 0.001; I = 0%). There were no significant differences in the overall side-effects between oral ketamine and the placebo group (RR 1.28, 95% CI: 0.89-1.83; p = 0.19).
This focused meta-analysis of oral ketamine suggests a marginal efficacy for major depressive disorder without increased risk of adverse events. Further larger sample studies are needed to confirm these preliminary findings, analyzing differential response/remission rates by affective disorder, optimal dosing strategies, and its long-term effects.
静脉注射氯胺酮已显示出强大的抗抑郁疗效，但目前还需要其他给药途径。我们进行了一项系统评价和荟萃分析，评估了口服氯胺酮治疗抑郁症的疗效和耐受性。
从成立到 2020 年 4 月，全面检索了主要电子数据库。纳入了评估口服氯胺酮治疗抑郁症的病例系列和随机临床试验。随机对照试验被纳入荟萃分析，重点关注反应、缓解、起效时间和副作用。
共检索到 917 篇文章，筛选出 890 项研究，共纳入 10 项系统评价研究。3 项随机对照试验（RCT）（N=161，平均年龄 37.9±9.5 岁，58.6%为女性）纳入荟萃分析。汇总分析提示口服氯胺酮具有显著的抗抑郁作用（SMD：-0.75；95%CI：-1.08，-0.43；p<0.0001；I=0%），但缓解率（RR：2.77；95%CI：0.96，8.00；p=0.06）和反应率（RR：2.58；95%CI：0.94，7.08；p=0.07）与安慰剂相比在终点时均为边缘性。口服氯胺酮的抗抑郁作用似乎在第 2 周起效（SMD：-0.71；95%CI：-1.08，-0.35；p=0.001；I=0%）。口服氯胺酮和安慰剂组的总体不良反应发生率无显著差异（RR 1.28，95%CI：0.89-1.83；p=0.19）。
本项针对口服氯胺酮的聚焦荟萃分析提示，其对重度抑郁症有一定疗效，但不会增加不良反应风险。需要进一步开展更大样本的研究来证实这些初步发现，并分析不同情感障碍的反应/缓解率、最佳剂量策略及其长期影响。
