Preliminary and ongoing French multicenter prospective naturalistic study of adverse events of antipsychotic treatment in naive children and adolescents

Background: The prescription of antipsychotics (AP), and especially second generation AP, is increasing worldwide in the pediatric population. Most prescriptions are off-label and despite the identification of frequent and potentially severe adverse events (AE), there are only a few guidelines for the safety management. France is one of the countries with no official safety guidelines. Methods: Psychotropic drug-naive adolescents (13-18 years), hospitalized for an acute psychotic episode and treated with a second-generation antipsychotic were consecutively included in a prospective cohort study. Patients were assessed for their AE at baseline, 2, 6 and 12 weeks after the introduction of drug. Results: The majority of patients was treated with risperidone (n = 13), 2 with aripiprazole. The principal findings are: (1) A high incidence of neuromuscular AE: 8/15 muscle weakness, 8/15 extrapyramidal syndrome, 6/15 akathisia, 3/15 oro-facial acute dystonia; (2) Severe catatonia symptoms in 2 patients despite a low to moderate treatment dose, requiring transfer in intensive care unit for one; (3) Weight gain and significant increase of the BMI for all 13 patients who had a 12 weeks follow-up. Conclusion: All adolescents experienced AE, with significant weight gain being observed in all patients who completed the 12-week follow-up. The fact that our patient population was first episode drug naive may partially explain this observation. Despite the limitation due to the small sample size of this prospective short-term study, such findings are important to report and warrant further research. Clinical and research implication: Because of the lack of naturalistic follow up studies of antipsychotic treatments in AP-naive children and adolescents and the absence of safety guidelines for the pediatric population in France, we decided to continue our research at a national level. We therefore started a prospective, naturalistic and multicenter study funded by the French National Agency for Medicines and Health Products Safety (ANSM). Study purpose is to evaluate the incidence of adverse events related to antipsychotic drugs in AP-naive children and adolescents. In addition, we aim to provide further evidence for the necessity of national safety guidelines for AP prescription in the pediatric population.