α7-烟碱型乙酰胆碱受体激动剂对精神分裂症认知缺陷和阴性症状治疗:随机双盲对照研究的meta分析（英文）

Alpha7 nAChR Agonists for Cognitive Deficit and Negative Symptoms in Schizophrenia:A Meta-analysis of Randomized Double-blind Controlled Trials

背景:现有α7-烟碱型乙酰胆碱受体激动剂(α7-nAChR受体激动剂)对精神分裂症的认知障碍和阴性症状治疗的临床研究结果不尽一致。目的:评估α7-烟碱型乙酰胆碱受体激动剂在治疗精神分裂症认知缺损和阴性症状的临床疗效和安全性。方法:PubMed、Embase、ClinicalTrials.gov、Cochrane Library和中国知网、万方、VIP数据库进行文献检索,检索时间截止于2017年5月26日。Meta分析双盲随机对照试验中α7-nAChR受体激动剂的作用,评估α7-nAChR受体激动剂对精神分裂症的总体认知功能和阴性症状的临床疗效。通过计算药物和安慰剂之间的平均差(SMDs),评估α7-nAChR受体激动剂能否作为有效的抗精神病药物。结果:8个低偏倚研究纳入了meta分析。我们没有发现α7乙酰受体激动剂对精神分裂症患者的认知障碍(SMD=-0.10(-0.46,0.25),I^2=88%)和阴性症状(SMD=0.13(-0.04,0.30),I^2=64%)有明显疗效。敏感性分析也印证了此结果。药物总体安全且耐受性良好,在不良事件(RR=1.02,[0.85,1.23])和脱落率(RR=1.04,[0.61,1.78])与安慰剂对照无显著差异。根据GRADE评级,该meta分析结果的证据强度为"中"。结论:α7-nAChR受体激动剂可能不是有效地改善精神分裂症患者总体认知障碍和的阴性症状的药物。

Background： Previous clinical trials of α7-nicotinic acetylcholine receptor agonists （α7-nAChR agonists） showed mixed results in treating the cognitive and negative symptoms of schizophrenia. Aims： To assess the efficacy and safety of α7-nAChR agonists in treating the cognitive and negative symptoms in schizophrenia. Methods： A literature search was conducted to identify randomized double-blind placebo-controlled trials for schizophrenia published before May 26, 2017, by searching PubMed, Embase, ClinicalTrials.gov, the Cochrane Library and the Chinese language databases CNKI, Wanfang, and VIP Data. The effects of α7-nAChR agonists were evaluated for overall cognitive function and negative symptoms by calculating standard mean difference （SMDs） between active drugs and placebo added to antipsychotics. Results： 8 studies with low bias were included. We found no statistically significant effects of α7 nAChR agonists on the overall cognitive function （SMD=-0.10[-0.46, 0.25], I^2 =88%） and negative symptoms （SMD=0.13 [-0.04, 0.30], I^2=64%） in patients with schizophrenia. Sensitivity analysis showed these results to be firm. And this drug is generally safe and well tolerated with no significant difference from placebo based on adverse events （RR=1.02, [0.85, 1.23]） and dropouts （RR=1.04, [0.61, 1.78]） data. Evidence based on outcomes from the meta-analysis was rated as ＇moderate＇ as per the GRADE guidelines. Conclusion： α7-nAChR agonists may not be effective in reversing overall cognitive impairments and negative symptoms in patients with schizophrenia as adjunctive therapies.