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Background
Autism spectrum disorder (ASD)is a developmental disorder affecting just below 1% of the world's population. Risperidone is an atypical antipsychotic drug used to treat irritability and aggression in children and adolescents with autism spectrum disorder. The aim of this study was to determine the therapeutic window for risperidone sum trough concentrations that balances weight gain with treatment effectiveness in this population. In addition, the effect of therapeutic drug monitoring (TDM) on treatment optimization was simulated.
Methods
In a retrospective cohort (n = 24 children), the target window for risperidone leading to the least increase in body mass index z-scores while retaining effectiveness as measured by the irritability subscale of the Aberrant Behavior Checklist was determined using receiver operating curve analysis. This target range was used to simulate the effect of TDM using a population PK model imple-mented in the software platform InsightRX. Dosing advice was based on plasma trough concentrations and the dose administered at 12 weeks to simulate whether more children would be on target at 24 weeks after the start of treatment.
Results
The simulated and observed dose and concentration data for 24 weeks are presented in Table 2. The difference in the sum trough concentration between the observed and simulated values at 24 weeks is schematically shown in Figure 2. Median dosesim was 0.43 mg (OR 0.20-0.60) a day. The intervention resulted in a signifcant decrease in dose(P=0.014) and sum trough concentration (P= 0.023) compared with doseobs (0.65 mg, IQR 0.50-1.00) with a median sum trough concentration of 7.55 mcg/L (OR 4.80-11.60).
The area under the curve of the ROC analysis for the BMI z-score was 0.801. Using the Youden index, the optimal upper cutoff value was a risperidone sum trough concentration of 8.46 mcg/L.
Conclusion
TDM may be a useful tool for optimizing risperidone treatment in children and adolescents with autism spectrum disorder.
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