The Effect of Kidney Function and Cardiovascular and Anti-Inflammatory Comedications on the Serum Concentration of Risperidone under Naturalistic Conditions

Polypharmacy has an important role in psychiatry, as the kidney function can be affected by medication. Risperidone is metabolized hepatically to 9-hydroxyrisperidone and excreted renally. Here, we study how serum concentrations of risperidone, 9-hydroxyrisperidone and active moiety (risperidone+9-hydroxyrisperidone) are related to impairment of kidney function and potentially interacting comedications that affect renal functions ((1) nonsteroidal anti-inflammatory drugs, (2) angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, and (3) diuretics). In this retrospective study, data from risperidone-treated inpatients (2015-2020, <i>n</i>=517) at the University Hospital of Würzburg were analyzed. Routine therapeutic drug monitoring was performed at trough levels at a steady-state. Groups were compared by means of the Kruskal-Wallis test. To correct for confounding parameters, additional multiple linear regression modeling was performed. After correction for age, sex, body mass index and the respective interaction between the estimated glomerular filtration rate and the number of interacting drugs, the dose-corrected serum concentration of 9-hydroxyrisperidone and the active moiety of risperidone were positively associated with the number of interacting drugs. The active moiety was negatively associated with the estimated glomerular filtration rate. Our data suggest that renal functions and the number of interacting drugs influence the pharmacokinetics of risperidone. Previous studies often explained the increasing serum concentration with age as a surrogate, whereas our results suggest that the kidney function and comedication affecting kidney function might be more relevant. When prescribing risperidone, especially in patients with renal impairment or co-medicated with interacting drugs, we suggest to start with lower starting doses and recommend monitoring serum concentrations to prevent overdosing.