Association Between Antipsychotic Treatment and Neurological Adverse Events in Pediatric Patients: A Population-Based Cohort Study in Korea

Abstract

Background: Potential adverse effects might be caused by increasing the number of antipsychotic prescriptions. However, the empirical evidence regarding pediatric psychiatric patients is insufficient. Therefore, we explored the antipsychotic-induced adverse effects focusing on the neurological system.Method: Using the medical information of pediatric patients retrieved from the claims data of Health Insurance Review and Assessment in Korea, we identified those psychiatric patients who were started on antipsychotic treatment at age 2–18 years between 2010 and 2018 (n = 10,969). In this study, movement disorders and seizures were considered as major neurological adverse events. The extended Cox model with time-varying covariates was applied to explore the association between antipsychotic medication and adverse events.Findings: Total 1,894 and 1,267 cases of movement disorders and seizures occurred in 32,046 and 33,280 person-years, respectively. The hazard risks of neurological adverse events were 3–8 times higher in the exposed to antipsychotics period than in the non-exposure period. Among the exposure periods, the most dangerous period was within 30 days of cumulative exposure. High doses or polypharmacy of antipsychotics was associated with increased risks of neurological adverse events. Among individual antipsychotics, haloperidol showed the highest risk of developing movement disorders among the examined agents. Quetiapine showed a lower risk of developing movement disorders but a higher risk of developing seizures than risperidone.Conclusion: These findings suggest that antipsychotics should be used with caution in pediatric patients, especially regarding initial exposure, high dose, and polypharmacy.

Association of Treatment With Antipsychotics, Antidepressants, or Both With Movement Disorders and Seizures Among Children and Adolescents With Depression in Korea

“…Aripiprazole is widely recognized as having a lower seizure risk than other agents 22,[47][48][49] ; in the previous studies conducted by our research group, risperidone showed a similar incidence risk of seizures. 22 Considering the slightly higher dose of aripiprazole than risperidone in the period of concomitant use, this discrepancy with previous findings may be attributed to differences in dosages for each agent. Among the drugs used concomitantly, the mean daily dose of aripiprazole was slightly higher than that of risperidone (risperidone, 109.11 mg/d vs aripiprazole, 117.52 mg/d).…”

“… 16 , 18 , 19 , 20 In previous studies conducted by some of us and other members of our research team, neurological AEs associated with antipsychotics (ie, movement disorder and seizure) were investigated in children and adolescents with psychotic disease using case-control 21 and cohort designs. 22 In the cohort study, 22 the hazard ratio (HR) for movement disorder during a period of antipsychotic use vs a period of nonuse was 8.17 (95% CI, 7.16-9.33) and for the development of seizure was 3.47 (95% CI, 2.99-4.03); furthermore, higher doses of antipsychotic polypharmacy were associated with increased risk of both AEs, and individual agents had slightly different safety profiles. Both study designs showed robust results, 21 , 22 indicating the need for careful monitoring and management of antipsychotic treatment in pediatric patients with psychotic disease regarding neurological AEs such as movement disorders and/or seizures.…”

“…In some studies, children and adolescents were more susceptible to some AEs, including extrapyramidal adverse effects, suggesting that these drugs might have different safety profiles in this population from those in adults . In previous studies conducted by some of us and other members of our research team, neurological AEs associated with antipsychotics (ie, movement disorder and seizure) were investigated in children and adolescents with psychotic disease using case-control and cohort designs . In the cohort study, the hazard ratio (HR) for movement disorder during a period of antipsychotic use vs a period of nonuse was 8.17 (95% CI, 7.16-9.33) and for the development of seizure was 3.47 (95% CI, 2.99-4.03); furthermore, higher doses of antipsychotic polypharmacy were associated with increased risk of both AEs, and individual agents had slightly different safety profiles.…”

Emergence of psychiatric adverse events during antipsychotic treatment in AP-naïve children and adolescents

“…However, several AEs remain poorly documented in AP-naïve pediatric patients [ 21 ], including psychiatric AEs [ 3 , 22 – 24 ]. The French ETAPE study is a 12-month naturalistic prospective multisite study that included 190 AP-naïve pediatric patients (mean age = 12 ± 3 years), treated by AP for psychotic or non-psychotic symptoms.…”

Emergence of psychiatric adverse events during antipsychotic treatment in naive children and adolescents

“…out a low level of adherence to follow-up guidelines concerning AP treatments in the pediatric population [19,20]. However, several AEs remain poorly documented in naïve pediatric patients [21], including psychiatric AEs [22,3,23,24]. The French ETAPE study is a 12-month naturalistic prospective multisite study that included 190 naïve pediatric patients (mean age = 12 ± 3 years), treated by AP for psychotic or nonpsychotic symptoms.…”