World Health Organization Collaborating Centre for Research and Training in Mental Health and Service Evaluation, and Department of Neuroscience, Biomedicine, and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy (Ostuzzi, Bertolini, Tedeschi, Gastaldon, Nosé, Ogheri, Papola, Purgato, Turrini, Barbui); Institute of Primary Health Care, University of Bern, Bern, Switzerland (Del Giovane); University Hospital of Verona, Verona, Italy (Bovo); Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, N.Y., Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, N.Y., and Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin (Correll).
Am J Psychiatry. 2021 May 1;178(5):424-436. doi: 10.1176/appi.ajp.2020.20071120. Epub 2021 Feb 18.
This study compared relapse prevention and acceptability of long-acting injectable (LAI) antipsychotics in the maintenance treatment of adults with nonaffective psychoses.
The authors searched MEDLINE, Embase, PsycINFO, CINAHL, CENTRAL, and online registers for randomized controlled trials published until June 2020. Relative risks and standardized mean differences were pooled using random-effects pairwise and network meta-analysis. The primary outcomes were relapse rate and all-cause discontinuation ("acceptability"). The quality of included studies was rated with the Cochrane Risk of Bias tool, and the certainty of pooled estimates was measured with GRADE (Grading of Recommendations Assessment, Development, and Evaluation).
Of 86 eligible trials, 78 (N=11,505) were included in the meta-analysis. Regarding relapse prevention, most of the 12 LAIs included outperformed placebo. The largest point estimates and best rankings of LAIs compared with placebo were found for paliperidone (3-month formulation) and aripiprazole. Moderate to high GRADE certainty for superior relapse prevention compared with placebo was also found for (in descending ranking order) risperidone, pipothiazine, olanzapine, and paliperidone (1-month formulation). In head-to-head comparisons of LAIs, only haloperidol was inferior to aripiprazole, fluphenazine, and paliperidone. For acceptability, most LAIs outperformed placebo, with moderate to high GRADE certainty for (in descending ranking order) zuclopenthixol, aripiprazole, paliperidone (3-month formulation), olanzapine, flupenthixol, fluphenazine, and paliperidone (1-month formulation). In head-to-head comparisons, only LAI aripiprazole had superior acceptability to other LAIs (bromperidol, fluphenazine, paliperidone [1-month formulation], pipothiazine, and risperidone).
LAI formulations of paliperidone (3-month formulation), aripiprazole, olanzapine, and paliperidone (1-month formulation) showed the highest effect sizes and certainty of evidence for both relapse prevention and acceptability. Results from this network meta-analysis should inform frontline clinicians and guidelines.
本研究比较了长效注射（LAI）抗精神病药在非情感性精神病成人维持治疗中的复发预防和可接受性。
作者检索了 MEDLINE、Embase、PsycINFO、CINAHL、CENTRAL 和在线登记册，以获取截至 2020 年 6 月发表的随机对照试验。使用随机效应成对和网络荟萃分析汇总相对风险和标准化均数差异。主要结局是复发率和全因停药（“可接受性”）。纳入研究的质量用 Cochrane 偏倚风险工具进行评估，汇总估计的确定性用 GRADE（推荐评估、制定和评估分级）进行测量。
在 86 项合格试验中，有 78 项（N=11505）纳入荟萃分析。关于复发预防，大多数纳入的 12 种 LAI 均优于安慰剂。与安慰剂相比，发现最具代表性的点估计值和最佳排名的 LAI 是帕利哌酮（3 个月制剂）和阿立哌唑。还发现与安慰剂相比，利培酮、哌泊噻嗪、奥氮平、帕利哌酮（1 个月制剂）具有较高的预防复发的中等至高度 GRADE 确定性（按降序排列）。在 LAI 头对头比较中，只有氟哌啶醇劣于阿立哌唑、氟奋乃静和帕利哌酮。对于可接受性，大多数 LAI 优于安慰剂，对于（按降序排列）齐拉西酮、阿立哌唑、帕利哌酮（3 个月制剂）、奥氮平、氟奋乃静、氟哌啶醇和帕利哌酮（1 个月制剂）具有中等至高度 GRADE 确定性。在头对头比较中，只有 LAI 阿立哌唑在可接受性方面优于其他 LAI（溴哌利多、氟奋乃静、帕利哌酮[1 个月制剂]、哌泊噻嗪和利培酮）。
帕利哌酮（3 个月制剂）、阿立哌唑、奥氮平和帕利哌酮（1 个月制剂）的 LAI 制剂在预防复发和可接受性方面显示出最高的效应量和证据确定性。本网络荟萃分析的结果应能为一线临床医生和指南提供信息。
