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

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 tau, 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 center dot 29 years, SD 2 center dot 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 center dot 00 kg (95% CI -3 center dot 61 to -0 center dot 39) with molindone to 5 center dot 60 kg (0 center dot 27 to 10 center dot 94) with haloperidol; BMI -0 center dot 70 kg/m(2) (-1 center dot 21 to -0 center dot 19) with molindone to 2 center dot 03 kg/m(2) (0 center dot 51 to 3 center dot 55) with quetiapine; total cholesterol -0 center dot 04 mmol/L (-0 center dot 39 to 0 center dot 31) with blonanserin to 0 center dot 35 mmol/L (0 center dot 17 to 0 center dot 53) with quetiapine; LDL cholesterol -0 center dot 12 mmol/L (-0 center dot 31 to 0 center dot 07) with risperidone or paliperidone to 0 center dot 17 mmol/L (-0 center dot 06 to 0 center dot 40) with olanzapine; HDL cholesterol 0 center dot 05 mmol/L (-0 center dot 19 to 0 center dot 30) with quetiapine to 0 center dot 48 mmol/L (0 center dot 18 to 0 center dot 78) with risperidone or paliperidone; triglycerides -0 center dot 03 mmol/L (-0 center dot 12 to 0 center dot 06) with lurasidone to 0 center dot 29 mmol/L (0 center dot 14 to 0 center dot 44) with olanzapine; fasting glucose from -0 center dot 09 mmol/L (-1 center dot 45 to 1 center dot 28) with blonanserin to 0 center dot 74 mmol/L (0 center dot 04 to 1 center dot 43) with quetiapine; prolactin from -2 center dot 83 ng/mL (-8 center dot 42 to 2 center dot 75) with aripiprazole to 26 center dot 40 ng/mL (21 center dot 13 to 31 center dot 67) with risperidone or paliperidone; heart rate from -0 center dot 20 bpm (-8 center dot 11 to 7 center dot 71) with ziprasidone to 12 center dot 42 bpm (3 center dot 83 to 21 center dot 01) with quetiapine; SBP from -3 center dot 40 mm Hg (-6 center dot 25 to -0 center dot 55) with ziprasidone to 10 center dot 04 mm Hg (5 center dot 56 to 14 center dot 51) with quetiapine; QTc from -0 center dot 61 ms (-1 center dot 47 to 0 center dot 26) with pimozide to 0 center dot 30 ms (-0 center dot 05 to 0 center dot 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. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.