Sex differences in side effects of antiseizure medications in pediatric patients with epilepsy: A systematic review.

PURPOSE: To perform a systematic review searching for differences in the side effects of antiseizure medications (ASMs) with respect to sex in pediatric patients with epilepsy.

METHODS

We carried out a comprehensive literature search of the PubMed database and all results up to April 2020 were included. Titles, abstracts, and full texts of the articles were screened by two independent reviewers. We included all studies evaluating the side effects of ASMs in patients with epilepsy younger than 18 years, with reference to the two sexes. Studies on ASMs used for indications other than epilepsy were excluded.

RESULTS

A total of 5164 studies were identified. Sixty-seven studies were finally included, 5 of them also including adult patients in the sample. Sixteen studies revealed sex-related differences in side effects of ASMs, disclosing a higher frequency of general side effects in girls: a higher risk of overweight, hyperammonaemia, high leptin levels, and carnitine deficiency in girls on valproic acid; a lower height increase, an increased risk of weight loss, the anecdotical occurrence of acute psychosis in girls on topiramate; a higher risk of retinal toxicity in boys on vigabatrin.

CONCLUSION

The effect of sex on susceptibility to side effects of ASMs is poorly investigated with sparse results, and it could be underestimated. The findings of our study point to the presence of sex differences which should be thoroughly investigated to be confirmed, highlighting the need for a systematic evaluation of sex as a determinant variable influencing the response to medications in clinical research.