Sex differences in antiseizure medications response in people with epilepsy: a systematic review

As a part of a wider project aimed to assess sex-related differences in adverse effects and efficacy of antiseizure medications (ASMs), we performed a systematic review focusing on differences in response to ASMs between males and females with epilepsy.

We conducted a comprehensive literature search in the PubMed database. The search was conducted without restriction on publication date, and all results up to September 2022 were included. We included all the articles written in English, Italian, Spanish, or French language evaluating the response to ASMs in people with epilepsy (PWE), with specific mention of the two sexes. The Newcastle-Ottawa Scale and the Jadad Scale were used to assess study quality.

A total of 1778 studies were identified. Of these, 60 studies searched for sex differences and among those, 46 (76%) did not identify statistically significant differences. Only 14 studies (23%) identified sex as a statistically significant variable in ASM efficacy. Among those, a greater number of studies reported higher rates of seizure reduction or seizure freedom in males using different ASMs, with 9 studies vs 5 in which drug response was higher in males.

Our study has identified male sex as a predictor of drug response in epilepsy in the majority of studies that found sex differences. However, the scarcity of data found in the literature highlights the need for a systematic evaluation of sex as a variable influencing the response to medications in clinical research.