The Effect of Age on Antipsychotic Serum Concentration in Males and Females: A Study Based on Therapeutic Drug Monitoring Data From 19,926 Patients.

Background: Antipsychotic medications are commonly prescribed for older patients; however, documentation on their safety and efficacy in this population is limited. This study aimed to investigate and compare the effect of age on dose-adjusted serum concentrations of 6 commonly used antipsychotic medications in both sexes.

Methods: Patients with serum concentration measurements of amisulpride, aripiprazole, clozapine, olanzapine, risperidone, and zuclopenthixol were retrospectively included from a therapeutic drug monitoring service. The primary outcome measure for each antipsychotic was the dose-adjusted serum concentration (C:D ratio), assessed across groups divided by sex and age (18-49 years, 50-74 years, and ≥75 years). The data were analyzed using linear mixed modeling with restricted maximum likelihood estimation.

Results: A total of 19,926 patients (53% male) with 74,194 serum concentration measurements were included. For most antipsychotics, the C:D ratios increased significantly with age, with generally larger differences observed in females compared with males. The largest impact of age was observed for risperidone, where C:D ratios in the age groups 50-74 years and ≥75 years were 20% and 81% higher for males, respectively, compared with the reference group (18-49 years). For females, the C:D ratios were 28% and 92% higher, respectively, compared with females aged 18-49 years (all P < 0.001). The smallest impact of age was observed for aripiprazole, with no significant differences in C:D ratios across age groups for males. For females treated with aripiprazole, C:D ratios were 8% and 28% higher in the 50-74 and ≥75 years age groups, respectively, compared with females aged 18-49 years (both P < 0.001).

Conclusions: The age-dependent increase in dose-adjusted serum concentrations among males and females varied across different antipsychotics and was highest for risperidone. These findings emphasize the importance of proper monitoring of antipsychotic use in older adults.