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Heterogeneity and efficacy of antipsychotic treatment for schizophrenia with or without treatment resistance: a meta-analysis.
Neuropsychopharmacology ( IF 7.6 ) Pub Date : 2019-11-25 , DOI: 10.1038/s41386-019-0577-3
Yuya Mizuno 1, 2 , Robert A McCutcheon 1, 3, 4 , Stefan P Brugger 3, 4, 5, 6, 7 , Oliver D Howes 1, 3, 4
Affiliation  

Two important clinical questions are whether there is a subtype of schizophrenia which responds differently to clozapine relative to other antipsychotics, and whether greater efficacy of clozapine is dependent on the degree of treatment-resistance. The authors address this by examining both variability and magnitude of response in patients treated with clozapine and other antipsychotics for both treatment-resistant schizophrenia (TRS) and non-resistant schizophrenia. Double-blind randomised controlled trials comparing clozapine with other antipsychotics in patients with schizophrenia were identified using five databases. Standard deviations and means of change in total, positive, and negative symptoms were extracted. Variability ratio (VR) and coefficient of variation ratio (CVR) were used to quantify relative variability in symptom change. Hedges' g was used to quantify mean differences. Ten TRS studies (n = 822) and 29 non-TRS studies (n = 2566) were meta-analysed. Relative variability in change of total symptoms did not differ significantly between clozapine and other antipsychotics in TRS studies (VR = 1.84; 95%CI, 0.85-4.02). These findings were similar with CVR, and for positive and negative symptoms. Clozapine was superior to other antipsychotics in improving total symptoms in both TRS (g = 0.34; 95%CI, 0.13-0.56) and non-TRS (g = 0.20; 95%CI, 0.08-0.32) studies. Furthermore, clozapine was superior in improving positive symptoms in both study groups, but not for negative symptoms. Pooled effect sizes showed no significant difference between TRS and non-TRS studies. These findings do not support a subtype of schizophrenia which responds specifically to clozapine. Clozapine is more effective than other antipsychotics irrespective of treatment-resistance, arguing for its use more generally in schizophrenia. PROSPERO CRD42018086507.

中文翻译:

抗精神病药物治疗精神分裂症的异质性和疗效(有或没有耐药):一项荟萃分析。

两个重要的临床问题是,相对于其他抗精神病药,是否存在一种对氯氮平有不同反应的精神分裂症亚型,以及氯氮平的更高疗效是否取决于治疗抵抗程度。作者通过检查接受氯氮平和其他抗精神病药治疗的耐药性精神分裂症(TRS)和非耐药性精神分裂症患者的变异性和反应幅度,来解决这一问题。使用五个数据库,确定了将氯氮平与其他抗精神病药在精神分裂症患者中进行比较的双盲随机对照试验。提取总体,阳性和阴性症状的标准偏差和变化方式。变异率(VR)和变异系数比(CVR)用于量化症状变化的相对变异性。Hedges的g用于量化均值差。荟萃分析了10篇TRS研究(n = 822)和29篇非TRS研究(n = 2566)。在TRS研究中,氯氮平和其他抗精神病药之间,总症状变化的相对变异性没有显着差异(VR = 1.84; 95%CI,0.85-4.02)。这些发现与CVR相似,并具有阳性和阴性症状。在改善TRS(g = 0.34; 95%CI,0.13-0.56)和非TRS(g = 0.20; 95%CI,0.08-0.32)研究的总症状方面,氯氮平优于其他抗精神病药。此外,在两个研究组中,氯氮平在改善阳性症状方面均较优,但对于阴性症状则无优势。合并效应量显示TRS研究与非TRS研究之间无显着差异。这些发现不支持对氯氮平有特殊反应的精神分裂症亚型。无论抗药性如何,氯氮平比其他抗精神病药都更有效,这表明氯氮平在精神分裂症中的使用更为广泛。PROSPERO CRD42018086507。
更新日期:2019-11-26
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