Off-label drug use in children and adolescents treated with antidepressants and antipsychotics: results from a prospective multicenter trial.

Background/objectives Off-label psychopharmacologic medication use is widespread in child and adolescent psychiatry, but little is known about its associated factors. This study aimed to assess frequency and determinants of off-label use of antidepressants and antipsychotics in youths in daily clinical practice. Methods In a prospective clinical study ('TDM-VIGIL') at 18 centers in three German-speaking countries, child psychiatric patients aged 4-18 years undergoing routine treatment with antidepressants and antipsychotics were systematically followed. Demographic, clinical and pharmacological data were collected in an online-based patient registry; off-label use was categorized by reasons, including age, indication or duration of treatment for each treatment episode. Examined correlates of off-label use included sex, treatment setting, diagnosis and illness severity. Results About 67% of all antidepressant and antipsychotic treatment episodes in the 700 included patients (mean age = 14.6 years, girls = 67%) were off-label. For antidepressants, 55.2% were off-label (age = 51.1%, non-licensed indications = 37.4%, age + indication = 11.5%), for antipsychotics 81.7% were off-label (age = 29.4%, non-licensed indications = 33.2%, age + indication = 37.4%). Sex, age (< 12, ≥ 12 years) as well as illness severity were not associated with off-label use. In antidepressant treatment, 'depression' and 'obsessive compulsive disorder' diagnoses were associated with reduced and 'suicidality at admission' with increased off-label prescriptions. In antipsychotics, 'schizophrenia diagnoses' was linked to decreased, university hospital treatment to increased off-label use. Conclusions The frequency of off-label use of antidepressants and even more of antipsychotics in youths treated at specialized child psychiatric centers is high. As the clinical efficacy and safety of off-label antidepressant and antipsychotic use in youth is under-researched, our results call for further pharmacovigilance studies and strategies to improve drug safety.