Antipsychotic Combinations vs Monotherapy in Schizophrenia: A Meta-analysis of Randomized Controlled Trials
Antipsychotic Combinations vs Monotherapy in Schizophrenia: A Meta-analysis of Randomized Controlled Trials
复制标题
DOI：
10.1093/schbul/sbn018
复制
发表时间：
2009-03-01
影响因子：
6.6
通讯作者：
Leucht, Stefan
中科院分区：
文献类型：
--
作者：
Correll, Christoph U.;Rummel-Kluge, Christine;Leucht, Stefan
内容：尽管缺乏安全性和有效性的证据，抗精神病药物联合治疗在精神分裂症中很常见。目的：评估抗精神病药物联合治疗与单药治疗精神分裂症的治疗和不良反应。数据来源：科克伦精神分裂症小组登记和相关期刊/会议记录的手动搜索。研究选择：比较抗精神病药物单药治疗与第二种抗精神病药物联合治疗的随机对照试验。数据提取和分析：两位作者独立提取数据。对于同质二分数据，我们计算了随机效应、相对风险（RR）、95%置信区间（CI）和需要治疗的人数（NNT）。对于连续数据，计算加权平均差。（1229例患者），28个单药治疗组和19个联合治疗组，抗精神病药物联合治疗在2个先验定义的共同主要结局方面上级单药治疗：研究特异性定义的无效较少（N = 22，n = 1202，RR = 0.76，CI = 0.63-0.90，P = .002，NNT = 7，CI = 4-17，P = .0008，I-2 = 78.9%）和全因停药（N = 20，n = 1052，RR = 0.65，CI = 0.54-0.78，P < .00001）。结果与临床总体不耐受阈值（P = 0.006）和最小改善（P = 0.01）一致。具体的精神病理学和不良事件数据不足以产生有意义的结果。在敏感性分析中，出现了5个疗效调节因素：同时开始多种药物治疗、氯氮平联合治疗、试验持续时间> 10周、中国试验和第二代+第一代抗精神病药物。在一个荟萃回归，类似的剂量组合，第二代+第一代抗精神病药物和并发多药启动仍然显着。结论：在某些临床情况下，抗精神病药物cotheating可能优于单药治疗上级。然而，该数据库可能存在发表偏倚，并且过于异质，无法得出可靠的临床建议，这强调了未来研究的必要性。
Context: Despite lacking evidence for its safety and efficacy, antipsychotic cotreatment is common in schizophrenia.Objective: To evaluate therapeutic and adverse effects of antipsychotic cotreatment vs monotherapy in schizophrenia.Data Sources: Cochrane Schizophrenia Group register and hand searches of relevant journals/conference proceedings.Study Selection: Randomized controlled trials comparing antipsychotic monotherapy to cotreatment with a second antipsychotic.Data Extraction and Analysis: Two authors independently extracted data. For homogenous dichotomous data, we calculated random effects, relative risk (RR), 95% confidence intervals (CIs), and numbers needed to treat (NNT). For continuous data, weighted mean differences were calculated.Results: In 19 studies (1229 patients) with 28 monotherapy and 19 cotreatment arms, antipsychotic cotreatment was superior to monotherapy regarding 2 a priori defined coprimary outcomes: less study-specific defined inefficacy (N = 22, n = 1202, RR = 0.76, CI = 0.63-0.90, P = .002, NNT = 7, CI = 4-17, P = .0008, I-2 = 78.9%) and all-cause discontinuation (N = 20, n = 1052, RR = 0.65, CI = 0.54-0.78, P < .00001). Results were consistent using Clinical Global Impressions thresholds of less than much (P = .006) and less than minimally (P = .01) improved. Specific psychopathology and adverse event data were insufficient to yield meaningful results. In sensitivity analyses, 5 efficacy moderators emerged: concurrent polypharmacy initiation, clozapine combinations, trial duration > 10 weeks, Chinese trials, and second-generation + first-generation antipsychotics. In a meta-regression, similar dose combinations, second-generation + first-generation antipsychotics and concurrent polypharmacy initiation remained significant.Conclusions: In certain clinical situations, antipsychotic cotreatment may be superior to monotherapy. However, the database is subject to possible publication bias and too heterogeneous to derive firm clinical recommendations, underscoring the need for future research.