One-year incidence rates of tardive dyskinesia in children and adolescents treated with second-generation antipsychotics: A systematic review

Objective: The aim of this study was to assess the 1-year risk of second-generation antipsychotics (SGAs) for tardive dyskinesia (TD) in children and adolescents with assumed minimal past exposure to first-generation antipsychotics. Method: We performed a systematic review and exploratory meta-analysis of long-term studies with SGAs, lasting at least 11 months and reporting on new cases of TD in patients less than 18 years old. Results: In 10 studies, 783 youth (mean age: 9.74 years, 79.2% prepubertal, 81.6% male, 78.4% white) received risperidone (n = 737, mean dose: 1.58 mg/day), quetiapine (n = 27, mean dose: 378.7 mg/day), or olanzapine (n = 19, mean dose: 10.4 mg/day) for a weighted mean of 329.6 days. Diagnoses included disruptive behavior disorders (n = 688, 87.9%), bipolar disorder (n = 52, 6.6%), schizophrenia/schizoaffective disorder (n = 26, 3.3%) and autism spectrum disorders (n = 17, 2.2%). Eight studies were open-label trials, two were retrospective chart reviews, and none included a comparator. Overall, three new cases of TD emerged during long-term treatment with SGAs of up to 3 years, resulting in crude and annualized TD rates of 0.38% (95% confidence interval, CI, 0.079-1.11) and 0.42% (95% CI, 0.087-1.24). The crude and annualized TD rates for risperidone (n = 737) were 0.27% (95% CI, 0.033-0.97) and 0.30% (95% CI, 0.037-1.10), respectively. In the two cases with information, TD resolved within weeks after antipsychotic discontinuation. Conclusions: Results across 10 studies suggest relatively low 1-year TD rates in pediatric patients treated with SGAs. However, the available data base is limited by the small sample size of studies with SGAs other than risperidone and by the use of relatively low doses, which may have obscured a potentially greater risk for TD in children and adolescents treated with higher total SGA doses and for longer durations. Large, long-term studies of various SGAs, using state-of-the art methodology, are needed before firm conclusions can be reached about the risk of TD in pediatric patients treated long-term with SGAs.