Age and Sex Differences in Adverse Events Associated With Antipsychotics: An Analysis of the FDA Adverse Events...

While the risks of antipsychotics in older adults are well recognized, clinical trials often exclude frail older patients, have short follow-up periods, and provide limited comparative data on specific drugs. This study aimed to explore age-related differences in the adverse effects of six commonly prescribed antipsychotics using a pharmacovigilance database, with additional analysis of sex-based variations.

We analyzed adverse event (AE) reports associated with aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and haloperidol from the FDA Adverse Event Reporting System (FAERS) database between Q4 2003 and Q2 2024. We utilized Standardized MedDRA Queries (SMQs) and self-defined queries to categorize 18 groups of AEs. Adjusted logistic regression was employed to calculate adjusted reporting odds ratios (aRORs) with 95% confidence intervals (CIs).

Our analysis revealed substance-specific differences in AE profiles. Risperidone had the highest aROR for hyperprolactinemia (aROR 212, 95% CI 203-221), haloperidol for dystonia (aROR 46, 95% CI 41-51), and aripiprazole for akathisia (aROR 45, 95% CI 42-49). Patients aged 65 and older generally demonstrated a higher likelihood of experiencing cardiac, extrapyramidal motor, and sedative AEs compared to those under 65, with few exceptions across the drugs investigated. In contrast, younger patients showed higher odds for metabolic AEs, including dyslipidemia and hyperglycemia (associated with olanzapine and quetiapine), as well as weight gain (with olanzapine, quetiapine, risperidone, and haloperidol). With few exceptions, women generally showed higher reporting odds of adverse events. Sex-related differences were especially pronounced for hyperprolactinemia, with 4.7-8.0 times higher reporting odds in women for aripiprazole, olanzapine, quetiapine, and haloperidol-except for risperidone, where a post-2014 rise in male reports led to higher odds in men. Risperidone was also associated with increased reporting odds of weight gain in men. Additionally, aripiprazole and olanzapine showed 3 to 6 times higher reporting odds for anticholinergic syndrome in men compared to women.

It is essential to consider both age and sex in treatment decisions to optimize the efficacy and tolerability of antipsychotic therapy.