Behavioral disorders, such as conduct disorder, influence choice of treatment and its outcome. Less is known about other variables that may have an influence.

We aimed to measure the parent drug and metabolite plasma levels in risperidone-treated children and adolescents with behavioral disorders and investigate the role of drug dose and patients’ gender and age.

We recruited 115 children/adolescents with DSM-5 behavioral disorders (females = 24; age range: 5–18 years) at the Departments of Psychiatry of the Hospitals of Bolzano, Italy, and Innsbruck, Austria. We measured risperidone and its metabolite 9-hydroxyrisperidone plasma levels and the parent drug-to-metabolite ratio in the plasma of all patients by using LC-MS/MS. A subsample of 15 patients had their risperidone doses measured daily. We compared risperidone and 9-hydroxyrisperidone plasma levels, as well as risperidone/9-hydroxyrisperidone ratio, in males vs. females and in younger (≤ 14 years) vs. older (15–18 years) patients by using Mann-Whitney U test. We fitted linear models for the variables “age” and “daily risperidone dose” by using log-transformation, regression analysis and applying the R2 statistic.

Females had significantly higher median 9-hydroxyrisperidone plasma levels (P = 0.000). Younger patients had a slightly lower median risperidone/9-hydroxyrisperidone ratio (P = 0.052). At the regression analysis, daily risperidone doses and metabolite, rather than parent drug–plasma levels were correlated (R2 = 0.35).

Gender is significantly associated with plasma levels, with females being slower metabolizers than males. Concerning age, younger patients seem to be rapid metabolizers, possibly due to a higher activity of CYP2D6. R2 suggests a clear-cut elimination of the metabolite.

The authors have not supplied their declaration of competing interest.