德国慕尼黑工业大学医学院Maximilian Huhn研究组近日取得一项新成果。他们比较分析了32种口服抗精神病药物治疗成人多发性精神分裂症的疗效和耐受性。 2019年9月14日出版的《柳叶刀》发表了相关论文。

研究组从各数据库建立之初一直检索至2019年1月8日，最终确定了54417篇文献，包含402项研究中53462名参与者的资料。对32种抗精神病药物安慰剂对照和随机对照试验进行荟萃分析，疗效规模评估表明，所有抗精神病药物与安慰剂相比均能减轻患者的总体症状。

标准化平均差异的范围从氯氮平的-0.89至左旋丙嗪的-0.03。与安慰剂相比，减轻阳性症状的标准化平均差异从氨磺必利的-0.69至布瑞哌唑的-0.17，减轻阴性症状从氯氮平的-0.62至氟哌噻吨的-0.10，减轻抑郁症状从舒必利的-0.90至氟哌噻吨的0.04。

与安慰剂相比，全因停药的风险比范围从氟哌噻吨的0.52至匹莫齐特的1.15，镇静风险比从匹莫齐特的0.92至珠氯噻醇的10.20，使用抗帕金森药物的风险比从氯氮平的0.46至匹莫齐特的6.14。体重增加的平均差异从齐拉西酮的-0.16 kg至佐替平的3.21 kg，催乳素升高从氯氮平的-77.05 ng/ml至帕利培酮的48.51 ng/ml，QTc延长从鲁拉西酮的-2.21 ms至舍吲哚的23.90 ms。

综上，抗精神病药物之间存在一些疗效差异，但大部分都是渐进而非离散的。副作用的差异更为明显。该研究结果将帮助临床医生权衡本国现有药物的风险和获益。

据悉，精神分裂症是全世界成年人中最常见、负担最重、花费最昂贵的精神疾病之一。抗精神病药物是治疗首选，但究竟该使用哪种药物存在争议。

附：英文原文

Title: Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis

Author: Maximilian Huhn, Adriani Nikolakopoulou, Johannes Schneider-Thoma, Marc Krause, Myrto Samara, Natalie Peter, Thomas Arndt, Lio Bckers, Philipp Rothe, Andrea Cipriani, John Davis, Georgia Salanti, Stefan Leucht

Issue&Volume: 2019/09/14

Summary: 

Background

Schizophrenia is one of the most common, burdensome, and costly psychiatric disorders in adults worldwide. Antipsychotic drugs are its treatment of choice, but there is controversy about which agent should be used. We aimed to compare and rank antipsychotics by quantifying information from randomised controlled trials.

Methods

We did a network meta-analysis of placebo-controlled and head-to-head randomised controlled trials and compared 32 antipsychotics. We searched Embase, MEDLINE, PsycINFO, PubMed, BIOSIS, Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov from database inception to Jan 8, 2019. Two authors independently selected studies and extracted data. We included randomised controlled trials in adults with acute symptoms of schizophrenia or related disorders. We excluded studies in patients with treatment resistance, first episode, predominant negative or depressive symptoms, concomitant medical illnesses, and relapse-prevention studies. Our primary outcome was change in overall symptoms measured with standardised rating scales. We also extracted data for eight efficacy and eight safety outcomes. Differences in the findings of the studies were explored in metaregressions and sensitivity analyses. Effect size measures were standardised mean differences, mean differences, or risk ratios with 95% credible intervals (CrIs). Confidence in the evidence was assessed using CINeMA (Confidence in Network Meta-Analysis). The study protocol is registered with PROSPERO, number CRD42014014919.

Findings

We identified 54?417 citations and included 402 studies with data for 53?463 participants. Effect size estimates suggested all antipsychotics reduced overall symptoms more than placebo (although not statistically significant for six drugs), with standardised mean differences ranging from −0·89 (95% CrI −1·08 to −0·71) for clozapine to −0·03 (−0·59 to 0·52) for levomepromazine (40?815 participants). Standardised mean differences compared with placebo for reduction of positive symptoms (31?179 participants) varied from −0·69 (95% CrI −0·86 to −0·52) for amisulpride to −0·17 (−0·31 to −0·04) for brexpiprazole, for negative symptoms (32?015 participants) from −0·62 (−0·84 to −0·39; clozapine) to −0·10 (−0·45 to 0·25; flupentixol), for depressive symptoms (19?683 participants) from −0·90 (−1·36 to −0·44; sulpiride) to 0·04 (−0·39 to 0·47; flupentixol). Risk ratios compared with placebo for all-cause discontinuation (42?672 participants) ranged from 0·52 (0·12 to 0·95; clopenthixol) to 1·15 (0·36 to 1·47; pimozide), for sedation (30?770 participants) from 0·92 (0·17 to 2·03; pimozide) to 10·20 (4·72 to 29·41; zuclopenthixol), for use of antiparkinson medication (24?911 participants) from 0·46 (0·19 to 0·88; clozapine) to 6·14 (4·81 to 6·55; pimozide). Mean differences compared to placebo for weight gain (28?317 participants) ranged from −0·16 kg (−0·73 to 0·40; ziprasidone) to 3·21 kg (2·10 to 4·31; zotepine), for prolactin elevation (21?569 participants) from −77·05 ng/mL (−120·23 to −33·54; clozapine) to 48·51 ng/mL (43·52 to 53·51; paliperidone) and for QTc prolongation (15?467 participants) from −2·21 ms (−4·54 to 0·15; lurasidone) to 23·90 ms (20·56 to 27·33; sertindole). Conclusions for the primary outcome did not substantially change after adjusting for possible effect moderators or in sensitivity analyses (eg, when excluding placebo-controlled studies). The confidence in evidence was often low or very low.

Interpretation

There are some efficacy differences between antipsychotics, but most of them are gradual rather than discrete. Differences in side-effects are more marked. These findings will aid clinicians in balancing risks versus benefits of those drugs available in their countries. They should consider the importance of each outcome, the patients' medical problems, and preferences.

DOI: 10.1016/S0140-6736(19)31135-3

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31135-3/fulltext