OBJECTIVES: Previous research has demonstrated gender differences in the clinical presentation of first episode psychosis (BMJ Open 2021, doi: 10.1136/bmjopen-2020-042949). However, less is known about gender differences related to the tolerability of antipsychotics used to treat psychotic disorders. We sought to investigate the associations of gender with clinician-recorded side effects by analyzing real-world data assembled from electronic health records (EHRs).

METHODS: De-identified EHR data were analyzed from the South London and Maudsley (SLaM) NHS Foundation Trust, UK using the Clinical Record Interactive Search tool (CRIS). Data on clinician-recorded side effects were obtained through manual review of unstructured EHR data. Altogether, 2,309 patients (male=64.6%) presenting to SLaM with first episode psychosis between April-01-2008 and March-31-2019 with ≥2 years of follow-up data were included in the study. The index date was the date of the first prescribed antipsychotic medication.

RESULTS: The most frequently prescribed antipsychotics were olanzapine (n=1,013; male=43.2%, female=45.0%), risperidone (n=571; male=26.1%, female=22.2%) and aripiprazole (n=460; male=20.1%, female=19.6%). Altogether, 709 male (47.5%) and 427 female (52.3%) patients had at least one clinician-recorded side effect (χ²=4.8, p=0.03). Male patients had similar rates of sedation (31.9% vs. 32.4%, χ2=0.07, p=0.79), extrapyramidal side effects (9.1% vs. 7.3%, χ2=2.1, p=0.14) and sexual side effects (3.8% vs. 5.1%, χ2=2.5, p=0.11) but lower rates of weight gain (16.7% vs. 22.2%, χ2=10.4, p=0.001) and hyperprolactinemia (3.2% vs. 7.2%, χ2=19.2, p<0.001) compared to female patients. Female patients discontinued their first-prescribed antipsychotic significantly earlier than male patients (hazard ratio (HR)=1.23, 95%CI=1.11-1.37).

CONCLUSIONS: Male patients were less likely to have weight gain or hyperprolactinemia recorded in EHR data whereas sedation, extrapyramidal side effects, and sexual side effects were similar compared to female patients. These differences, along with other potentially confounding variables, may explain the greater rate of antipsychotic discontinuation among female patients and highlight a need to tailor treatment options for first episode psychosis accordingly.