Comparative physiological effects of antipsychotic drugs in children and young people: a network meta-analysis

IF 19.9 1区 医学 Q1 PEDIATRICS Lancet Child & Adolescent Health Pub Date : 2024-06-17 DOI:10.1016/S2352-4642(24)00098-1
Maria Rogdaki MRCPsych , Robert A McCutcheon MRCPsych , Enrico D'Ambrosio MD , Valentina Mancini PhD , Cameron J Watson MD , Jack B Fanshawe MBChB , Richard Carr MD , Laurence Telesia MRCPsych , Maria Giulia Martini MD , Aaron Philip MRCPsych , Barnabas J Gilbert MRCPsych , Gonzalo Salazar-de-Pablo MD , Marinos Kyriakopoulos FRCPsych , Prof Dan Siskind MD , Prof Christoph U Correll MD , Prof Andrea Cipriani MD , Orestis Efthimiou PhD , Prof Oliver D Howes MRCPsych , Toby Pillinger MRCPsych
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With network meta-analysis, we aimed to investigate the effects of various antipsychotic medications on physiological variables in children and adolescents with neuropsychiatric and neurodevelopmental conditions.</p></div><div><h3>Methods</h3><p>For this network meta-analysis, we searched Medline, EMBASE, PsycINFO, Web of Science, and Scopus from database inception until Dec 22, 2023, and included randomised controlled trials comparing antipsychotics with placebo in children or adolescents younger than 18 years with any neuropsychiatric and neurodevelopmental condition. Primary outcomes were mean change from baseline to end of acute treatment in bodyweight, BMI, fasting glucose, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, prolactin, heart rate, systolic blood pressure (SBP), and QT interval corrected for heart rate (QTc) for patients receiving either active treatment or placebo. For multigroup trials reporting several doses, we calculated a summary value for each physiological variable for all doses. After transitivity assessment, we fitted frequentist random-effects network meta-analyses for all comparisons in the network. A Kilim plot was used to summarise the results for all treatments and outcomes, providing information regarding the strength of the statistical evidence of treatment effects, using p values. Network heterogeneity was assessed with τ, risk of bias of individual trials was assessed with the Cochrane Collaboration's Tool for Assessing Risk of Bias, and the credibility of findings from each network meta-analysis was assessed with the Confidence in Network Meta-Analysis (CINEMA) app. This study is registered on PROSPERO (CRD42021274393).</p></div><div><h3>Findings</h3><p>Of 6676 studies screened, 47 randomised controlled trials were included, which included 6500 children (mean age 13·29 years, SD 2·14) who received treatment for a median of 7 weeks (IQR 6–8) with either placebo (n=2134) or one of aripiprazole, asenapine, blonanserin, clozapine, haloperidol, lurasidone, molindone, olanzapine, paliperidone, pimozide, quetiapine, risperidone, or ziprasidone (n=4366). Mean differences for bodyweight change gain compared with placebo ranged from –2·00 kg (95% CI –3·61 to –0·39) with molindone to 5·60 kg (0·27 to 10·94) with haloperidol; BMI –0·70 kg/m<sup>2</sup> (–1·21 to –0·19) with molindone to 2·03 kg/m<sup>2</sup> (0·51 to 3·55) with quetiapine; total cholesterol –0·04 mmol/L (–0·39 to 0·31) with blonanserin to 0·35 mmol/L (0·17 to 0·53) with quetiapine; LDL cholesterol –0·12 mmol/L (–0·31 to 0·07) with risperidone or paliperidone to 0·17 mmol/L (–0·06 to 0·40) with olanzapine; HDL cholesterol 0·05 mmol/L (–0·19 to 0·30) with quetiapine to 0·48 mmol/L (0·18 to 0·78) with risperidone or paliperidone; triglycerides –0·03 mmol/L (–0·12 to 0·06) with lurasidone to 0·29 mmol/L (0·14 to 0·44) with olanzapine; fasting glucose from –0·09 mmol/L (–1·45 to 1·28) with blonanserin to 0·74 mmol/L (0·04 to 1·43) with quetiapine; prolactin from –2·83 ng/mL (–8·42 to 2·75) with aripiprazole to 26·40 ng/mL (21·13 to 31·67) with risperidone or paliperidone; heart rate from –0·20 bpm (–8·11 to 7·71) with ziprasidone to 12·42 bpm (3·83 to 21·01) with quetiapine; SBP from –3·40 mm Hg (–6·25 to –0·55) with ziprasidone to 10·04 mm Hg (5·56 to 14·51) with quetiapine; QTc from –0·61 ms (–1·47 to 0·26) with pimozide to 0·30 ms (–0·05 to 0·65) with ziprasidone.</p></div><div><h3>Interpretation</h3><p>Children and adolescents show varied but clinically significant physiological responses to individual antipsychotic drugs. 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引用次数: 0

Abstract

Background

The degree of physiological responses to individual antipsychotic drugs is unclear in children and adolescents. With network meta-analysis, we aimed to investigate the effects of various antipsychotic medications on physiological variables in children and adolescents with neuropsychiatric and neurodevelopmental conditions.

Methods

For this network meta-analysis, we searched Medline, EMBASE, PsycINFO, Web of Science, and Scopus from database inception until Dec 22, 2023, and included randomised controlled trials comparing antipsychotics with placebo in children or adolescents younger than 18 years with any neuropsychiatric and neurodevelopmental condition. Primary outcomes were mean change from baseline to end of acute treatment in bodyweight, BMI, fasting glucose, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, prolactin, heart rate, systolic blood pressure (SBP), and QT interval corrected for heart rate (QTc) for patients receiving either active treatment or placebo. For multigroup trials reporting several doses, we calculated a summary value for each physiological variable for all doses. After transitivity assessment, we fitted frequentist random-effects network meta-analyses for all comparisons in the network. A Kilim plot was used to summarise the results for all treatments and outcomes, providing information regarding the strength of the statistical evidence of treatment effects, using p values. Network heterogeneity was assessed with τ, risk of bias of individual trials was assessed with the Cochrane Collaboration's Tool for Assessing Risk of Bias, and the credibility of findings from each network meta-analysis was assessed with the Confidence in Network Meta-Analysis (CINEMA) app. This study is registered on PROSPERO (CRD42021274393).

Findings

Of 6676 studies screened, 47 randomised controlled trials were included, which included 6500 children (mean age 13·29 years, SD 2·14) who received treatment for a median of 7 weeks (IQR 6–8) with either placebo (n=2134) or one of aripiprazole, asenapine, blonanserin, clozapine, haloperidol, lurasidone, molindone, olanzapine, paliperidone, pimozide, quetiapine, risperidone, or ziprasidone (n=4366). Mean differences for bodyweight change gain compared with placebo ranged from –2·00 kg (95% CI –3·61 to –0·39) with molindone to 5·60 kg (0·27 to 10·94) with haloperidol; BMI –0·70 kg/m2 (–1·21 to –0·19) with molindone to 2·03 kg/m2 (0·51 to 3·55) with quetiapine; total cholesterol –0·04 mmol/L (–0·39 to 0·31) with blonanserin to 0·35 mmol/L (0·17 to 0·53) with quetiapine; LDL cholesterol –0·12 mmol/L (–0·31 to 0·07) with risperidone or paliperidone to 0·17 mmol/L (–0·06 to 0·40) with olanzapine; HDL cholesterol 0·05 mmol/L (–0·19 to 0·30) with quetiapine to 0·48 mmol/L (0·18 to 0·78) with risperidone or paliperidone; triglycerides –0·03 mmol/L (–0·12 to 0·06) with lurasidone to 0·29 mmol/L (0·14 to 0·44) with olanzapine; fasting glucose from –0·09 mmol/L (–1·45 to 1·28) with blonanserin to 0·74 mmol/L (0·04 to 1·43) with quetiapine; prolactin from –2·83 ng/mL (–8·42 to 2·75) with aripiprazole to 26·40 ng/mL (21·13 to 31·67) with risperidone or paliperidone; heart rate from –0·20 bpm (–8·11 to 7·71) with ziprasidone to 12·42 bpm (3·83 to 21·01) with quetiapine; SBP from –3·40 mm Hg (–6·25 to –0·55) with ziprasidone to 10·04 mm Hg (5·56 to 14·51) with quetiapine; QTc from –0·61 ms (–1·47 to 0·26) with pimozide to 0·30 ms (–0·05 to 0·65) with ziprasidone.

Interpretation

Children and adolescents show varied but clinically significant physiological responses to individual antipsychotic drugs. Treatment guidelines for children and adolescents with a range of neuropsychiatric and neurodevelopmental conditions should be updated to reflect each antipsychotic drug's distinct profile for associated metabolic changes, alterations in prolactin, and haemodynamic alterations.

Funding

UK Academy of Medical Sciences, Brain and Behaviour Research Foundation, UK National Institute of Health Research, Maudsley Charity, the Wellcome Trust, Medical Research Council, National Institute of Health and Care Research Biomedical Centre at King's College London and South London and Maudsley NHS Foundation Trust, the Italian Ministry of University and Research, the Italian National Recovery and Resilience Plan, and Swiss National Science Foundation.

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抗精神病药物对儿童和青少年生理效应的比较:网络荟萃分析
背景儿童和青少年对各种抗精神病药物的生理反应程度尚不清楚。为了进行这项网络荟萃分析,我们检索了 Medline、EMBASE、PsycINFO、Web of Science 和 Scopus,检索时间从数据库建立之初到 2023 年 12 月 22 日,并纳入了在 18 岁以下患有任何神经精神疾病和神经发育疾病的儿童或青少年中比较抗精神病药物与安慰剂的随机对照试验。主要结果是接受积极治疗或安慰剂的患者的体重、体重指数、空腹血糖、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、甘油三酯、催乳素、心率、收缩压 (SBP) 和根据心率校正的 QT 间期 (QTc) 从基线到急性治疗结束的平均变化。对于报告了多个剂量的多组试验,我们计算了所有剂量下每个生理变量的汇总值。在进行转换性评估后,我们对网络中的所有比较进行了频数随机效应网络荟萃分析。基利姆图用于总结所有治疗方法和结果的结果,使用 p 值提供有关治疗效果统计证据强度的信息。网络异质性采用τ进行评估,个别试验的偏倚风险采用Cochrane合作组织的偏倚风险评估工具进行评估,每个网络荟萃分析结果的可信度采用网络荟萃分析置信度(CINEMA)应用程序进行评估。本研究已在 PROSPERO(CRD42021274393)上注册。研究结果在筛选出的 6676 项研究中,47 项随机对照试验被纳入其中,共纳入 6500 名儿童(平均年龄 13-29 岁,SD 2-14 岁),他们接受了安慰剂(n=2134)或阿立哌唑(n=2134)治疗,治疗时间中位数为 7 周(IQR 6-8)、阿塞那平、布洛南色林、氯氮平、氟哌啶醇、鲁拉西酮、莫林酮、奥氮平、帕利哌酮、匹莫齐德、喹硫平、利培酮或齐拉西酮中的一种(n=4366)。与安慰剂相比,体重增加变化的平均差异为:莫林酮-2-00千克(95% CI -3-61至-0-39),氟哌啶醇-5-60千克(0-27至10-94);BMI:莫林酮-0-70千克/平方米(-1-21至-0-19),喹硫平-2-03千克/平方米(0-51至3-55);总胆固醇-0-04 毫摩尔/升(-0-39 至 0-31)(使用布洛南色林)至 0-35 毫摩尔/升(0-17 至 0-53)(使用喹硫平);低密度脂蛋白胆固醇-0-12 毫摩尔/升(-0-31 至 0-07)(使用利培酮或帕利哌酮)至 0-17 毫摩尔/升(-0-06 至 0-40)(使用奥氮平);高密度脂蛋白胆固醇 喹硫平为 0-05 毫摩尔/升(-0-19 至 0-30),利培酮或帕利哌酮为 0-48 毫摩尔/升(0-18 至 0-78);甘油三酯:使用鲁拉西酮为-0-03 毫摩尔/升(-0-12 至 0-06),使用奥氮平为 0-29 毫摩尔/升(0-14 至 0-44);空腹血糖:使用布隆色林为-0-09 毫摩尔/升(-1-45 至 1-28),使用喹硫平为 0-74 毫摩尔/升(0-04 至 1-43);使用阿立哌唑时,催乳素从-2-83 纳克/毫升(-8-42 至 2-75)升至使用利培酮或帕利哌酮时的 26-40 纳克/毫升(21-13 至 31-67);心率:齐拉西酮为-0-20 bpm(-8-11 至 7-71),喹硫平为 12-42 bpm(3-83 至 21-01);SBP:齐拉西酮为-3-40 mm Hg(-6-25 至 -0-55),喹硫平为 10-04 mm Hg(5-56 至 14-51);QTc:皮莫齐德为-0-61 ms(-1-47 至 0-26),齐拉西酮为 0-30 ms(-0-05 至 0-65)。解释儿童和青少年对各种抗精神病药物的生理反应各不相同,但都具有临床意义。针对患有各种神经精神疾病和神经发育疾病的儿童和青少年的治疗指南应予以更新,以反映每种抗精神病药物在相关代谢变化、催乳素改变和血流动力学改变方面的独特特征。资助机构英国医学科学院、大脑与行为研究基金会、英国国家健康研究所、莫兹利慈善机构、惠康基金会、医学研究委员会、伦敦国王学院国家健康与护理研究所生物医学中心、南伦敦和莫兹利 NHS 基金会、意大利大学与研究部、意大利国家恢复与复原计划以及瑞士国家科学基金会。
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来源期刊
Lancet Child & Adolescent Health
Lancet Child & Adolescent Health Psychology-Developmental and Educational Psychology
CiteScore
40.90
自引率
0.80%
发文量
381
期刊介绍: The Lancet Child & Adolescent Health, an independent journal with a global perspective and strong clinical focus, presents influential original research, authoritative reviews, and insightful opinion pieces to promote the health of children from fetal development through young adulthood. This journal invite submissions that will directly impact clinical practice or child health across the disciplines of general paediatrics, adolescent medicine, or child development, and across all paediatric subspecialties including (but not limited to) allergy and immunology, cardiology, critical care, endocrinology, fetal and neonatal medicine, gastroenterology, haematology, hepatology and nutrition, infectious diseases, neurology, oncology, psychiatry, respiratory medicine, and surgery. Content includes articles, reviews, viewpoints, clinical pictures, comments, and correspondence, along with series and commissions aimed at driving positive change in clinical practice and health policy in child and adolescent health.
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