# The Impact of Sex and Age on Antipsychotic Serum Concentrations

## TL;DR

This study shows that women, especially younger ones, have higher blood levels of certain antipsychotics than men, suggesting the need for sex-specific dosing guidelines.

## Contribution

The study identifies age- and sex-specific differences in antipsychotic drug levels, emphasizing the need for personalized treatment approaches.

## Key findings

- Women had higher clozapine and olanzapine levels than men, but not quetiapine or aripiprazole.
- Young women (<45) showed higher clozapine and olanzapine levels than men, but this difference disappeared in older women.
- Clozapine levels in women decreased significantly after age 55, while no such trend was seen for other drugs.

## Abstract

Estrogen affects drug metabolism for specific antipsychotics, which may produce sex differences in serum levels, especially over the menopausal transition. Here, we explore sex differences in concentrations of four commonly used antipsychotics: clozapine, olanzapine, aripiprazole, and quetiapine and examined how these vary across age groups, including postmenopause (>55).

Antipsychotic concentrations of 44 378 serum samples drawn between January 2016 and October 2024 were analyzed. Samples were provided by 6147 unique adult men and women for clozapine (n = 34 761 samples, 26% female), olanzapine (n = 5114, 27% female), aripiprazole (n = 3171, 37% female), and quetiapine (n = 1332, 50% female). To investigate the effect of sex and age on antipsychotic concentrations, we employed linear mixed-effects models and pairwise contrasts by dividing the samples in 6 groups according to sex and age (<45, 45-55, and >55 years).

We found higher concentrations in women compared to men for clozapine (P < .001), and olanzapine (P < .001), but not for quetiapine or aripiprazole. Young women (<45) showed higher levels of clozapine (P = .004) and olanzapine (P < .001) than men, but older women did not. Clozapine levels were higher in women <45 and 45-55 compared to women >55 years (all P < .05). For olanzapine, aripiprazole, and quetiapine concentrations differences between female age groups were absent.

We found sex differences in olanzapine and clozapine concentrations, which were most pronounced until 45 years of age. Our findings suggest that monitoring antipsychotic levels may add clinical value and underscore the need for sex-specific prescription guidelines for olanzapine and clozapine.