Abstract
IMPORTANCE: Little evidence exists on neurological adverse events (movement disorders and seizures) that occur during adjuvant use of antipsychotics with antidepressants, especially in children and adolescents. OBJECTIVE: To assess the association between neurological adverse events (movement disorders, including parkinsonism, dystonia, extrapyramidal symptoms, chorea, and tic, and seizures) and the adjuvant use of antipsychotics in children and adolescents with depression. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study using the Health Insurance Review and Assessment claims database in Korea between 2008 and 2018. The study population was children and adolescents aged 2 to 18 years with depression who began treatment with antidepressants between January 1, 2010, and December 31, 2018. Data were analyzed between December 9, 2020, and December 10, 2021. EXPOSURE: Time-varying exposure to antidepressants, antipsychotics, and concomitant use of antidepressants and antipsychotics. Concomitant use was further subdivided according to the antipsychotic treatment status (dose and agent). MAIN OUTCOMES AND MEASURES: The extended Cox proportional hazards regression model, with adjustment for sex, age, health insurance type, psychiatric comorbidities, psychiatric hospitalization, and comedication with other psychotropic drugs, was used to estimate adjusted hazard ratios (aHRs) and 95% CIs for the associations of movement disorders and seizures with use of antidepressants and antipsychotics. RESULTS: A total of 9890 patients were included in the study: 9541 (mean [SD] age, 14.8 [2.8] years; 4956 [51.9%] female) and 7731 (mean [SD] age, 14.9 [2.7] years; 4150 [53.7%] female) met the inclusion criteria for movement disorders and seizures, respectively. For movement disorders, associations were found between concomitant use (aHR, 3.68; 95% CI, 3.06-4.44) and antipsychotic-only use (aHR, 3.84; 95% CI, 3.03-4.87) compared with antidepressant-only use, but their CIs overlapped. The associations with seizure were similar (concomitant use: aHR, 2.06; 95% CI, 1.66-2.55; antipsychotic-only use: aHR, 2.05; 95% CI, 1.53-2.75). With concomitant use, the aHRs gradually increased with increasing doses of antipsychotics. Haloperidol had the highest aHR, 7.15 (95% CI, 3.89-10.00) for movement disorders. The highest aHR for seizure was observed with quetiapine (aHR, 2.36; 95% CI, 1.55-3.59), followed by aripiprazole (aHR, 2.05; 95% CI, 1.52-2.77). CONCLUSIONS AND RELEVANCE: In this cohort study, adjunctive antipsychotics with antidepressants were associated with movement disorders and seizures compared with antidepressant monotherapy in children and adolescents with depression. These results suggest that careful consideration of the risk-benefit profile of the antipsychotic use as adjuvant therapy in this population is needed.