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
{"title":"Comparative physiological effects of antipsychotic drugs in children and young people: a network meta-analysis","authors":"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","doi":"10.1016/S2352-4642(24)00098-1","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>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.</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. 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.</p></div><div><h3>Funding</h3><p>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.</p></div>","PeriodicalId":54238,"journal":{"name":"Lancet Child & Adolescent Health","volume":null,"pages":null},"PeriodicalIF":19.9000,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352464224000981/pdfft?md5=5136a7bece6d21517bf312af58b56656&pid=1-s2.0-S2352464224000981-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lancet Child & Adolescent Health","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2352464224000981","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PEDIATRICS","Score":null,"Total":0}
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.
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.