Efficacy of 42 Pharmacologic Cotreatment Strategies Added to Antipsychotic Monotherapy in Schizophrenia Systematic Overview and Quality Appraisal of the Meta-analytic Evidence
Efficacy of 42 Pharmacologic Cotreatment Strategies Added to Antipsychotic Monotherapy in Schizophrenia Systematic Overview and Quality Appraisal of the Meta-analytic Evidence
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DOI：
10.1001/jamapsychiatry.2017.0624
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发表时间：
2017-07-01
期刊：
影响因子：
25.8
通讯作者：
Leucht, Stefan
中科院分区：
文献类型：
--
作者：
Correll, Christoph U.;Rubio, Jose M.;Leucht, Stefan
精神分裂症有限的治疗反应促使了抗精神病药物与第二种精神药物联合治疗的试验。缺乏对多种药物联合治疗疗效的综合评价。目的总结和比较经荟萃分析确定的成人精神分裂症患者抗精神病药物联合用药策略的疗效。数据来源系统检索PubMed和PsycInfo，截止2016年5月13日。研究选择：随机临床试验荟萃分析，比较抗精神病药物联合其他抗精神病或非抗精神病药物与安慰剂或抗精神病单药治疗在成年精神分裂症患者中的疗效。数据提取与综合独立审稿人提取数据，并使用评估系统评价的测量工具（AMSTAR）评估纳入的meta分析方法的质量，增加6个新项目来评估其质量。效应量，表示为标准化平均差/对冲系数g或风险比，分别比较与任何抗精神病药物的联合和与氯氮平的联合。主要结局和测量：主要结局为总症状减轻。次要结局包括阳性和阴性症状、作者推荐的治疗方法、研究确定的无效、认知和抑郁症状、因任何原因停止治疗、无效或不耐受性。结果：在3397篇文献中，29项荟萃分析在381项单独试验中检验了42种联合策略，共纳入了19833名受试者。对于总的症状减轻，32种策略增加任何抗精神病药物和5种策略增加氯氮平进行了检查。14个联合治疗优于对照组（标准平均差/对冲系数g， -1.27 [95% CI, -2.35至-0.19]至-0.23 [95% CI, -0.44至-0.02]；P= 0.05）。没有与氯氮平联合的策略优于对照组。meta分析方法的质量总体较高（平均得分为9分，最高得分为11分），但meta分析研究的质量较低（平均得分为2.8分，最高得分为8分）。治疗建议与效应大小相关(相关系数，0.22;95% CI, 0.35-0.10； P
IMPORTANCE Limited treatment responses in schizophrenia prompted the testing of combining an antipsychotic drug treatment with a second psychotropic medication. A comprehensive evaluation of the efficacy of multiple medication combinations is missing.OBJECTIVE To summarize and compare the meta-analytically determined efficacy of pharmacologic combination strategies of antipsychotic drugs in adults with schizophrenia.DATA SOURCES Systematic search of PubMed and PsycInfo until May 13, 2016.STUDY SELECTION Meta-analyses of randomized clinical trials comparing the efficacy of antipsychotic drugs combined with other antipsychotic or nonantipsychotic medications vs placebos or antipsychotic monotherapy among adults with schizophrenia.DATA EXTRACTION AND SYNTHESIS Independent reviewers extracted the data and assessed the quality of the methods of the included meta-analyses using A Measurement Tool to Assess Systematic Reviews (AMSTAR), adding 6 new items to rate their quality. Effect sizes, expressed as standardized mean difference /Hedges g or risk ratio, were compared separately for combinations with any antipsychotic drug and for combinations with clozapine.MAIN OUTCOMES AND MEASURES The primary outcome was total symptom reduction. Secondary outcomes included positive and negative symptoms, treatment recommendations by authors, study-defined inefficacies, cognitive and depressive symptoms, discontinuation of treatment because of any cause, and inefficacies or intolerabilities.RESULTS Of 3397 publications, 29 meta-analyses testing 42 combination strategies in 381 individual trials and among 19 833 participants were included. For total symptom reductions, 32 strategies that augmented any antipsychotic drug and 5 strategies that augmented clozapine were examined. Fourteen combination treatments outperformed controls (standard mean difference/Hedges g, -1.27 [95% CI, -2.35 to -0.19] to -0.23 [95% CI, -0.44 to -0.02]; P=.05). No combination strategies with clozapine outperformed controls. The quality of the methods of the meta-analyses was generally high (mean score, 9 of a maximum score of 11) but the quality of the meta-analyzed studies was low (mean score, 2.8 of a maximum score of 8). Treatment recommendations correlated with the effect size (correlation coefficient, 0.22; 95% CI, 0.35-0.10; P