艾司氯胺酮鼻腔喷雾剂辅助治疗难治性抑郁症安全性meta分析

Meta-analysis of the Safety of Esketamine Nasal Spray Add-on Therapy for Treatment-resistant Depression

目的采用meta分析全面了解艾司氯胺酮鼻腔喷雾剂辅助治疗难治性抑郁症的安全性。方法搜索艾司氯胺酮鼻腔喷雾剂+口服抗抑郁药的随机对照试验,并进行meta分析。结果最终5个随机对照试验,1019例患者纳入研究。与对照组比较,试验组出现了更多的解离症状(RR=6.35,95%CI,2.84~14.23,P<0.00001)、镇静(RR=5.47,95%CI,2.05~14.57,P=0.0007)、嗜睡(RR=2.66,95%CI,1.30~5.44,P=0.007)、头痛(RR=1.38,95%CI,1.05~1.83,P=0.02)、眩晕(RR=5.87,95%CI,3.30~69.79,P<0.00001)、头晕(RR=2.98,95%CI,1.33~6.68,P=0.008)、感觉迟钝(RR=10.25,95%CI,3.65~28.83,P<0.0001)、焦虑(RR=2.01,95%CI,1.20~3.37,P=0.008)、感觉异常(RR=6.62,95%CI,2.75~15.98,P<0.0001)、恶心(RR=4.05,95%CI,2.71~6.05,P<0.00001)、味觉异常(RR=1.81,95%CI,1.35~2.42,P<0.0001)。亚组分析显示,与对照组比较,艾司氯胺酮鼻腔喷雾剂28 mg组不良反应没有统计学意义;除了嗜睡、头痛、味觉异常以外,56,84 mg 2个亚组的不良反应有统计学意义。结论艾司氯胺酮鼻腔喷雾剂辅助治疗会增加患者不良反应,但是不良反应轻微。

OBJECTIVE To evaluate the safety of esketamine nasal spray add-on therapy for treatment-resistant depression by meta analysis.METHODS Randomized controlled trials(RCTs)of esketamine nasal spray+oral antidepressants were searched and meta-analysis was conducted.RESULTS Five RCTs and 1019 patients were included in the study.Compared with contrast group,treatment group had more adverse reacions,such as dissociation(RR=6.35,95%CI,2.84–14.23,P<0.00001);sedation(RR=5.47,95%CI,2.05–14.57,P=0.0007);somnolence(RR=2.66,95%CI,1.30–5.44,P=0.007);headache(RR=1.38,95%CI,1.05–1.83,P=0.02);vertigo(RR=5.87,95%CI,3.30–69.79,P<0.00001;diziness(RR=2.98,95%CI,1.33–6.68,P=0.008);hypoesthesia(RR=10.25,95%CI,3.65–28.83,P<0.0001);anxiety(RR=2.01,95%CI,1.20–3.37,P=0.008);paresthesia(RR=6.62,95%CI,2.75–15.98,P<0.0001);nausea(RR=4.05,95%CI,2.71–6.05,P<0.00001);dysguesia(RR=1.81,95%CI,1.35–2.42,P<0.0001).At the same time,compared with contrast group,in esketamine nasal spray 28 mg subgroup,it had no significant difference in adverse effects;while in 56,84 mg subgroup,there was significant difference besides of somnolence,headache,dysguesia.CONCLUSION It is showed that the appearance of adverse events has increased,but it is very light in esketamine nasal spray add-on therapy for treatment-resistant depression.