Antipsychotic treatment is associated with metabolic disturbance, with clear differences observed between drugs in the adult population. However, the degree to which metabolic alterations occur with different antipsychotics in children and adolescents is unclear. As such, we aimed to compare and rank antipsychotics based on their metabolic and endocrine side-effects when used in the treatment of schizophrenia in this age population.

We searched MEDLINE, EMBASE, and PsycINFO from inception until October 30, 2022. We included double blinded, randomised controlled trials comparing 12 antipsychotics and placebo in acute treatment of schizophrenia in individuals aged <18 years. We performed random-effects network meta-analyses to investigate treatment-induced changes in body weight, BMI, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, glucose, and prolactin concentrations. We performed meta-regressions to examine the relationship between metabolic/endocrine change and age, sex, and ethnicity

Of 6697 citations, we included 15 randomised controlled trials, consisting of 2501 patients. Antipsychotics included in analyses were aripiprazole, asenapine, blonanserin, clozapine, haloperidol, lurasidone, molindone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone. Median treatment duration was 6 weeks (IQR 6-12). Mean age was 15.13 (SD 0.94) years. Mean differences for weight gain compared with placebo ranged from -2.04 kg (95% CI -4.24 to 0.17) kg for molindone to 4.11 kg (-0.55 to 8.77) for clozapine; for BMI from -0.55 kg/m2 (-1.37 to 0.27) for molindone to 1.92 kg/m2 (0.16 to 3.68) for quetiapine; for total cholesterol from -0.14 mmol/L (-0.70 to 0.41) for risperidone/paliperidone to 0.46 mmol/L (0.00 to 0.90) for quetiapine; for LDL cholesterol from -0.32 mmol (-0.76 to 0.12) for aripiprazole to 0.24 mmol/L (-0.15 to 0.63) for olanzapine; for HDL cholesterol from 0.10 mmol/L (-0.05 to 0.26) for aripiprazole to -0.23 mmol/L (-0.52 to 0.06) for risperidone/paliperidone; for triglycerides from -0.01 mmol/L (-0.21 to 0.34) for molindone to 0.62 mmol/L (0.04 to 1.2) for clozapine; for glucose from -0.33 mmol/L (-0.64 to -0.02) for ziprasidone to 0.81 mmol/L (0.28 to 1.34) for clozapine; for prolactin from -1.92 ng/mL (-15.37 to 11.53) for aripiprazole to 28.10 ng/mL (16.23 to 39.96) for risperidone/paliperidone. Higher baseline age predicted by greater increases in body weight (p = 0.014).

We found significant differences between antipsychotics in terms of metabolic and endocrine side-effects when used in children and adolescents. Treatment guidelines should be updated to reflect our findings. However, the choice of antipsychotic should be made on an individual basis, considering the clinical circumstances and preferences of young people, carers, and clinicians.