Use of adjuvant antipsychotics in children treated for depression may be associated with movement disorders

1. This cohort study concluded that the concurrent use of antipsychotics and antidepressants in children was associated with movement disorders, as well as seizures.

2. Haloperidol was found to have the strongest association with movement disorders and quetiapine the strongest association with seizure disorders.

Assessment of the level of proof: 2 (good)

Summary of the study: The addition of antipsychotic drugs to an adult antidepressant regimen to treat mood disorders is well established, despite some lingering drug safety concerns. These concerns are particularly pronounced in the pediatric population. This study aimed to assess associations between combined antipsychotic and antidepressant treatment and common side effects in children. 9890 participants were followed in total; of these, 9541 had a diagnosed movement disorder and 7731 had a diagnosed seizure disorder. 10% of patients diagnosed with a movement disorder or epilepsy following their first antidepressant treatment had used an antipsychotic concomitantly. The overall risk of a movement disorder increased with the combined use of an antipsychotic and an antidepressant, or the monotherapy use of an antipsychotic drug compared with the use of an antidepressant alone. The risk of a movement disorder was highest among haloperidol users, and the risk of a seizure disorder was highest among those who had used multiple concomitant antipsychotic medications. This retrospective study from South Korea demonstrated significant differences in the rates of movement disorders and seizures in children and youth who were treated with antipsychotic medications alone or in combination with antidepressants, compared to those who took antidepressants alone. Given recent increases in the rate of prescribing antipsychotics among young people, it is important to understand the risk profile of these medications. A strength of this study is the large sample size and long data collection period. However, one of the main limitations of this work includes the potential for misclassification bias, as most of the data came from a large database and no data on treatment adherence or concomitant medication use/ medication was not available. Moreover, the retrospective nature of this work makes it impossible to control for confounding factors.

Click here to read this article in JAMA Network Open

Relevant reading: Antipsychotic prescribing and relevant safety monitoring practices in children and youth: a population-based study in Alberta, Canada

In depth [retrospective cohort study]: Data for this study were obtained from a national healthcare claims database in Korea, dating from January 1, 2008 to December 31, 2018. Eligible patients were between the ages of 2 and 18 and had been diagnosed with depression for which they had been treated with at least one antidepressant medication. The combination therapy cohort included patients who had been treated with an antidepressant plus one or more of the following antipsychotic drugs: risperidone, aripiprazole, quetiapine, olanzapine, haloperidol. The primary outcome was a diagnosis of movement disorder, including: parkinsonism, dystonia, extrapyramidal symptoms, chorea, and tic. The incidence rate of a movement disorder per 100 person-years among the following groups was as follows: 1.14 for nonusers, 3.64 among users of antidepressants alone, 19.48 among users of antipsychotics alone and 17.29 for concomitant use. The adjusted relative risk compared to users of antidepressants alone for the risk of movement disorder in concurrent users was 3.69 (95% confidence interval 3.06-4.44) and 3.84 (3 .03-4.87) for users of antipsychotics alone. Similarly, the crude incidence rates per 100 person-years for seizures were: 1.35 for non-use, 4.46 for use of antidepressants only, 10.60 for use of antipsychotics only and 9.91 for concomitant use. Adjusted hazard ratios (aHR) for seizures were 2.06 (1.66-2.55) in concurrent users and 2.05 (1.53-2.75) in antipsychotic users alone compared to users of antidepressants alone. =The risk of movement disorder in users of various antipsychotic drugs was as follows: haloperidol (aHR, 7.15; 3.89-10.00), followed by polypharmacy (aHR, 6.15; 4.60- 8.20), aripiprazole (aHR, 3.57; 2.83-4.50), risperidone (aHR, 3.14; 2.41-4.08), olanzapine (aHR, 2.63; 1.23-5.64) and quetiapine (aHR, 2.20; 1.42-3.40). The risk of seizure disorder associated with the use of antipsychotics was as follows: polypharmacy (aHR, 2.92; 2.02-4.22), quetiapine (aHR, 2.36; 1.55-3.59) , aripiprazole (aHR, 2.05; 1.52-2.77) and risperidone (aHR, 1.55; 1.08-2.21).

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