Zhu Yikang, Krause Marc, Huhn Maximilian, Rothe Philipp, Schneider-Thoma Johannes, Chaimani Anna, Li Chunbo, Davis John M, Leucht Stefan
Department of Psychiatry and Psychotherapy, Technische Universität München, Klinikum rechts der Isar, Munich, Germany; Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Centre, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Psychiatry and Psychotherapy, Technische Universität München, Klinikum rechts der Isar, Munich, Germany.
Lancet Psychiatry. 2017 Sep;4(9):694-705. doi: 10.1016/S2215-0366(17)30270-5. Epub 2017 Jul 20.
The first episode of schizophrenia is a pivotal phase of this debilitating illness. Which drug to use remains controversial without a summary of all direct or indirect comparisons of drugs. We did a systematic review with pairwise and network meta-analyses of efficacy and tolerability.
We searched MEDLINE, Embase, PsycINFO, Cochrane Library, PubMed, Biosis, and ClinicalTrials.gov for randomised controlled trials of antipsychotics for the acute treatment of first-episode schizophrenia, published up to Nov 17, 2016. Our primary outcome was overall change in symptoms. Secondary outcomes were change in positive and negative symptoms, categorical response to treatment, study dropout for any reason and for inefficacy of treatment, use of drugs to treat parkinsonian symptoms, weight gain, sedation, increase in prolactin release, overall functioning, and quality of life. We did the meta-analyses with a random-effects model to calculate standardised mean differences (SMDs) or odds ratios (ORs) with 95% CIs.
We identified 19 relevant randomised controlled trials of 12 antipsychotic drugs that involved 2669 participants. 13 of the studies presented data on the primary outcome. For overall reduction of symptoms, amisulpride (SMD -0·37, 95% CI -0·61 to -0·14), olanzapine (-0·25, -0·39 to -0·12), ziprasidone (-0·25, -0·48 to -0·01), and risperidone (-0·14, -0·27 to -0·01) were significantly more efficacious than haloperidol, but the evidence was very low to moderate quality. Amisulpride was superior for reduction of symptoms to quetiapine (SMD -0·25, 95% CI -0·50 to -0·01). Olanzapine was superior to haloperidol and risperidone for reduction of negative symptoms. Several second-generation antipsychotics were superior to haloperidol in terms of all-cause discontinuation. Olanzapine was associated with at least one use of drugs to treat parkinsonian symptoms and quetiapine with less akathisia than haloperidol, aripiprazole, risperidone, and olanzapine, but, again, evidence was very low to low quality. Molindone was superior to risperidone, haloperidol, and olanzapine in terms of weight gain, and superior to risperidone in terms of increase in prolactin release.
Haloperidol seems to be a suboptimum treatment option for acute treatment of first-episode schizophrenia, but we found little difference between second-generation antipsychotics. The evidence was generally of low quality and the numbers of patients for each drug were small. Thus, the choice of treatment should be guided primarily by side-effects.
German Federal Ministry of Education and Research.
精神分裂症的首发是这种致残性疾病的关键阶段。在没有对药物进行所有直接或间接比较总结的情况下，使用哪种药物仍存在争议。我们进行了一项系统评价，并对疗效和耐受性进行了成对和网状荟萃分析。
我们检索了MEDLINE、Embase、PsycINFO、Cochrane图书馆、PubMed、Biosis和ClinicalTrials.gov，以查找截至2016年11月17日发表的关于抗精神病药物用于首发精神分裂症急性治疗的随机对照试验。我们的主要结局是症状的总体变化。次要结局包括阳性和阴性症状的变化、治疗的分类反应、因任何原因和治疗无效导致的研究退出、用于治疗帕金森症状的药物使用、体重增加、镇静作用、催乳素释放增加、总体功能和生活质量。我们使用随机效应模型进行荟萃分析，以计算标准化均数差（SMD）或比值比（OR）及95%置信区间。
我们确定了12种抗精神病药物的19项相关随机对照试验，涉及2669名参与者。其中13项研究提供了主要结局的数据。对于症状的总体减轻，氨磺必利（SMD -0·37，95% CI -0·61至-0·14）、奥氮平（-0·25，-0·39至-0·12）、齐拉西酮（-0·25，-0·48至-0·01）和利培酮（-0·14，-0·27至-0·01）比氟哌啶醇显著更有效，但证据质量非常低至中等。氨磺必利在减轻症状方面优于喹硫平（SMD -0·25，95% CI -0·50至-0·01）。奥氮平在减轻阴性症状方面优于氟哌啶醇和利培酮。几种第二代抗精神病药物在全因停药方面优于氟哌啶醇。奥氮平与至少一次使用治疗帕金森症状的药物有关，喹硫平的静坐不能比氟哌啶醇、阿立哌唑、利培酮和奥氮平少，但同样，证据质量非常低至低。吗茚酮在体重增加方面优于利培酮、氟哌啶醇和奥氮平，在催乳素释放增加方面优于利培酮。
氟哌啶醇似乎不是首发精神分裂症急性治疗的最佳选择，但我们发现第二代抗精神病药物之间差异不大。证据质量普遍较低，每种药物的患者数量较少。因此，治疗选择应主要以副作用为指导。
德国联邦教育与研究部。
