Abstract
Antipsychotics are known to cause cardiovascular and metabolic adverse effects, but there is less evidence for their use off-label, especially in children and adolescents. Such treatments may be administered over long durations. We conducted a systematic review to examine the cardiometabolic adverse effects of prolonged antipsychotic treatment in children and adolescents with non-psychotic disorders. We searched for randomised clinical trials and observational studies lasting for a year or more, examining the adverse outcomes of weight gain, hyperglycaemia, dyslipidaemia, hypertension, metabolic syndrome, ischaemic heart disease, and thrombosis. There were no randomised trials, and 15 observational studies involved 114,141 participants with mean age of 10.9 years (range of means 4.3-14.9 years). Twelve antipsychotics were covered but the majority (12 studies, 80%) examined risperidone. Using the vote counting method, long-term antipsychotic treatment was associated with weight gain (91.6% studies, n = 12), hyperglycaemia (100%, n = 6), dyslipidaemia (66.6%, n = 6), and metabolic syndrome (100%, n = 2). Hypertension was demonstrated in only one study (25%, n = 4), and none examined ischaemic heart disease or thrombosis. Studies exhibited moderate to high methodological quality. Prolonged exposure to antipsychotics during childhood may be associated with several metabolic adverse effects that could have long-term health impacts. Longer-term studies on a wider range of agents are required to clarify risks and develop appropriate strategies to mitigate them. Antipsychotic prescribing for children should be assessed on an individual basis, after weighing the benefits of therapy against the harms that may arise. Children need to be monitored for these metabolic effects, and early intervention is essential if adverse effects are severe.