Safety and tolerability of antipsychotic drugs in pediatric patients: data from an ongoing active pharmacovigilance study in Sicily

Background: Antipsychotic drugs are increasingly used to treat a variety of psychiatric disorders in children and adolescents. However, these medications are frequently used outside of their therapeutic indications. For this reason, a higher level of attention regarding the safety and tolerability profile of these drugs is necessary. Aim: To perform an integrated assessment of the risk and tolerability profile associated with the use of antipsychotic drugs (both typical and atypical) in pediatric patients, with a focus on the identification of suspected adverse drug reactions (ADRs). Methods: Starting from April 2017 pediatric patients followed by 5 units of developmental age neuropsychiatry who initiated a treatment with at least an antipsychotic drug (ATC class N05A) where included into the study, regardless of diagnosis and concomitant administration of other drugs. Data relative to patient’s characteristics, therapy, use indications, clinical and laboratory examinations have been collected at the time of treatment initiation and regularly thereafter into a dedicated database. Results: To date, 129 patients (84 males and 45 females, mean age ± SD of 13.6 ± 3.4 years) were enrolled into the study, 99 (76.7%) of them were assisted as outpatients, 25 (19.4%) as inpatients and 5 (3.8%) in day care regimen. Fifty-six patients were initially treated with risperidone, 46 with aripiprazole, 10 with olanzapine, 5 with clozapine, 3 with levomepromazine, 3 with quetiapine, 3 with haloperidol, 1 with asenapine, 1 with clotiapine and 1 with periciazine. The most represented diagnoses, classified according to the ICD10, were: attention-deficit hyperactivity disorder (n=31), autistic disorder (n=30), mild intellectual disabilities (n=16), Tourette's disorder (n=14), oppositional defiant disorder (n=13) and obsessive-compulsive disorder (n=12). In total, we observed 207 ADRs with the most frequent being weight increase (n=31), hyperfagia (n=21), hyperprolactinemia (n=17) and hypercholesterolaemia (n=14). Among the 48 cases of ADR reported into the Italian pharmacovigilance network only 7 (14.6%) were of the serious and were represented by elevated creatinine phosphokinase (n=2), QTc interval prolongation (n=2), dystonia (n=1), leucopenia (n=1) and hyperprolactinemia (n=1). Conclusions: These preliminary data trace a safety profile for antipsychotics in pediatric patients similar to the one already laid down for adults. However, more data are necessary in order to evaluate risk and tolerability of these drugs when used in pediatric patients.