Short- and long-term effects on prolactin of risperidone and olanzapine treatments in children and adolescents.

This study investigated prolactin levels in two groups of children and adolescents receiving risperidone (N=29) or olanzapine (N=13). It focused not only on significant differences but also on effect sizes; took into account dose effects and gender differences; used a longitudinal design (months 1, 3, 6 and 12) that helped control for individual differences; and took into account response differences due to the duration of antipsychotic treatment. Additionally, this study investigated tolerance development using statistical tests, and explored the effect of antipsychotic plasma concentrations at months 1 and 3. After adjusting for gender, treatment duration and individual effects, mean prolactin levels on risperidone were 4.9 ng/mL higher than on olanzapine (10.3 times higher after controlling for dosing potency). On risperidone treatment, the adjusted mean prolactin level at the 3rd month of treatment was significantly higher than at the 1st month; at the 12th month it was significantly lower than at the 1st month; the 1st and 6th months were not significantly different. On olanzapine treatment, adjusted mean prolactin levels at the 3rd and 6th months of treatment were significantly higher than at the 1st month; at the 12th month it was lower than at the 1st month, but the difference was not significant. In males, at the 3rd month, an increase of 1 ng/mL in plasma 9-hydroxyrisperidone concentrations raised prolactin levels significantly by 0.44 ng/mL. In females, independently of duration (1 or 3 months), an increase of 1 ng/mL in plasma olanzapine concentrations raised prolactin levels significantly by 2.1 ng/mL. After adjusting for dose and the greater potency of risperidone, the increase in prolactin levels during risperidone treatment appeared to be 10.3 times higher than that during olanzapine treatment. Our study showed a pattern consistent with the development of prolactin tolerance over time. Future prolactin studies in children and adolescents taking antipsychotics need to include larger samples with more frequent prolactin measures and long-term plasma concentrations.