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], I2 =88%) and negative symptoms (SMD=0.13 [-0.04, 0.30], I2 =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.
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), I2 = 88%) 和阴性症状(SMD =0.13(-0.04,0.30), I2 = 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。.
Keywords: cognitive dysfunction; meta-analysis; nicotinic agonists; schizophrenia.