Incidence of adverse events in antipsychotic-naïve children and adolescents treated with antipsychotic drugs: Results of a multicenter naturalistic study (ETAPE)

•The off-label prescription of antipsychotics is on the rise. There is a significant lack of data on drug safety and adverse events in the short as well as in the long term.•Off-label prescription of AP is frequently. ETAPE finds a high incidence and persistence rate of AEs during follow-up.•Antipsychotic treatment in pediatric population needs systematic monitoring and follow-up of adverse events. The main objective of ETAPE study was to determine the incidence of adverse events (AEs) potentially related to antipsychotic (AP) during a 12-months observational study of naturalistic treatment. ETAPE is a naturalistic prospective multicenter study conducted between April 2013 and May 2016. 200 patients were included. The mean age was 12 ± 3 years, with 73.6% being males. Patients presented a significant clinical improvement over time. At baseline, 92% of patients received a second generation AP, 74% AP monotherapy and 79.5% off-label AP prescriptions. Clinical diagnoses were heterogeneous including psychosis, anxiety, mood and neurodevelopmental disorders. The overall AE incidence rate was 11.52 AEs per person-years. Among AEs potentially attributable to AP, 15.4% were neuromotor, 14.8% gastroenterological, 12.2% metabolic and 11.8% general symptoms. Weight and body mass index increased significantly. More than half of AE appeared during the first 3 months, but onset of AE was noted all over follow-up. The presence of AEs was stable over time. ETAPE study highlights a high incidence rate of AE in children treated with AP. A careful and continuous clinical and biological monitoring is required to adapt treatment decisions based on benefice-risk-analysis. Moreover, additional research is warranted, also in regard of high proportion of off-label prescriptions.