Efficacy for Psychopathology and Body Weight and Safety of Topiramate-Antipsychotic Cotreatment in Patients With Schizophrenia Spectrum Disorders: Results From a Meta-Analysis of Randomized Controlled Trials
Efficacy for Psychopathology and Body Weight and Safety of Topiramate-Antipsychotic Cotreatment in Patients With Schizophrenia Spectrum Disorders: Results From a Meta-Analysis of Randomized Controlled Trials
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DOI：
10.4088/jcp.15r10373
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发表时间：
2016-06-01
影响因子：
5.3
通讯作者：
Cohen, Dan
中科院分区：
文献类型：
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作者：
Correll, Christoph U.;Maayan, Lawrence;Cohen, Dan
目的：荟萃分析托吡酯-抗精神病药物联合治疗精神分裂症的疗效和耐受性。数据来源：使用关键词托吡酯和抗精神病药物 * 或neurolept* 或特定抗精神病药物名称检索PubMed/MEDLINE数据库，直至2015年9月5日。研究选择：托吡酯的随机对照试验（RCT）-抗精神病药物联合治疗与安慰剂和持续抗精神病药物治疗的精神分裂症谱系障碍患者。数据提取：两名评估者提取数据。标准化平均差（SMD），加权平均差（WMD），和风险比（RR）+/-95%CIs.Results：在8个随机对照试验，持续平均+/- SD为13.6 +/- 4.9周，439例患者被随机托吡酯（100-400 mg/d）与安慰剂（试验= 7）或正在进行的抗精神病药物治疗（试验= 1）。托吡酯在总体精神病理学方面优于对照药物（试验= 6，n = 269，SMD = -0.57 [95% CI，-1.01至-0.14]，P = .01），阳性症状（试验= 4，n = 190，SMD = -0.56 [95% CI，-1.0至-0.11]，P = .01），阴性症状（试验= 4，n = 190，SMD = -0.62 [95% CI，-1.13至-0.10]，P = 0.02）一般精神病理学（试验= 3，n = 179，SMD = -0.69 [95% CI，-1.27至-0.11]，P = .02），体重（试验= 7，n = 327，WMD = -3.14 kg [95% CI，-5.55至-0.73]，P = .01）和体重指数（BMI）（试验= 4，n = 198，WMD = -1.80 [95% CI，-2.77至-0.84]，P = .0003）。托吡酯对总体精神病理学和体重减轻效应的疗效不受试验持续时间、托吡酯剂量、性别、年龄、住院状态、基线阳性和阴性综合征量表或基线BMI的介导/调节。相反，与托吡酯-非氯氮平抗精神病药联合治疗相比，氯氮平-托吡酯联合治疗的疗效更好，但体重减轻更少。托吡酯组和对照组的全因停药率相似（试验= 7，RR = 1.24 [95%CI，0.76 - 2.02]，P = 0.39）。与安慰剂相比，托吡酯仅倾向于更多的感觉异常（试验= 4，RR = 2.03 [95% CI，0.99至4.18]，P = 0.05）。结论：托吡酯-抗精神病药联合治疗显著降低精神分裂症谱系障碍患者的总体、阳性、阴性和一般精神病理学以及体重/BMI，同时耐受性良好。然而，需要更大规模的研究来证实和扩展这些发现。(C)版权所有2016 Physicians Postgraduate Press，Inc.
Objective: To meta-analyze the efficacy and tolerability of topiramate-antipsychotic cotreatment in schizophrenia.Data Sources: PubMed/MEDLINE database were searched until September 5, 2015, using the keywords topiramate AND antipsych* OR neurolept* OR specific antipsychotic names.Study Selection: Randomized controlled trials (RCTs) of topiramate-antipsychotic cotreatment versus placebo and ongoing antipsychotic treatment in patients with schizophrenia spectrum disorders were included.Data Extraction: Two evaluators extracted data. Standardized mean difference (SMD), weighted mean difference (WMD), and risk ratio (RR) +/- 95% CIs were calculated.Results: In 8 RCTs, lasting a mean +/- SD of 13.6 +/- 4.9 weeks, 439 patients were randomized to topiramate (100-400 mg/d) versus placebo (trials = 7) or ongoing antipsychotic treatment (trial = 1). Topiramate outperformed the comparator regarding total psychopathology (trials = 6, n = 269, SMD = -0.57 [95% CI, -1.01 to -0.14], P = .01), positive symptoms (trials = 4, n = 190, SMD = -0.56 [95% CI, -1.0 to -0.11], P = .01), negative symptoms (trials = 4, n = 190, SMD = -0.62 [95% CI, -1.13 to -0.10], P = .02) general psychopathology (trials = 3, n = 179, SMD = -0.69 [95% CI, -1.27 to -0.11], P = .02), body weight (trials = 7, n = 327, WMD = -3.14 kg [95% CI, -5.55 to -0.73], P = .01), and body mass index (BMI) (trials = 4, n = 198, WMD = -1.80 [95% CI, -2.77 to -0.84], P = .0003). Topiramate's efficacy for total psychopathology and weight reduction effects were not mediated/moderated by trial duration, topiramate dose, sex, age, inpatient status, baseline Positive and Negative Syndrome Scale, or baseline BMI. Conversely, clozapine-topiramate cotreatment moderated greater efficacy, but less weight loss, compared to topiramate-nonclozapine antipsychotic combinations. All-cause discontinuation was similar between topiramate and control groups (trials = 7, RR = 1.24 [95% CI, 0.76 to 2.02], P = .39). Topiramate trended only toward more paresthesia than placebo (trials = 4, RR = 2.03 [95 % CI, 0.99 to 4.18], P = .05).Conclusions: Topiramate-antipsychotic cotreatment significantly reduced total, positive, negative, and general psychopathology and weight/BMI in patients with schizophrenia spectrum disorder while being well tolerated. However, larger studies are needed to confirm and extend these findings. (C) Copyright 2016 Physicians Postgraduate Press, Inc.