Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2021 Feb;35(2):161-176.
doi: 10.1007/s40263-021-00794-0. Epub 2021 Feb 12.

Sex Differences in the Risk of Cutaneous Adverse Drug Reactions Induced by Antiseizure Medications: A Systematic Review and Meta-analysis

Israa Alfares  1 , Muhammad Shahid Javaid  2 , Zhibin Chen  2 , Alison Anderson  2 , Ana Antonic-Baker  2 , Patrick Kwan  3   4
Affiliations
Meta-Analysis

Sex Differences in the Risk of Cutaneous Adverse Drug Reactions Induced by Antiseizure Medications: A Systematic Review and Meta-analysis

Israa Alfares et al. CNS Drugs. 2021 Feb.

Abstract

Background: Cutaneous adverse drug reactions (cADRs) are one of the most common, severe, and life-threatening types of adverse reactions following treatment with antiseizure medications (ASMs). Some studies have reported a higher incidence of ASM-induced cADRs in females than in males.

Objective: This study sought to perform a systematic review, meta-analysis, and meta-regression to compare the ASM cADR risks between females and males.

Methods: We searched the literature using three databases (EMBASE, PubMed, and Web of Science) between October 1998 and November 2018, later updated to October 2019. Studies were included in the meta-analysis if they met the following criteria: (1) observational studies that estimated the incidence of cADRs related to ASMs; (2) provided the risk or odds ratio (OR) for cADRs among female and male patients exposed to ASMs; and (3) provided information on patients' characteristics. We assessed the impact of study characteristics, publication bias, and measures to reduce bias, and performed a DerSimonian and Laird random effects meta-analysis.

Results: We included 28 studies in this review. Of these, seven studies were eligible for inclusion in the meta-analysis, involving a total of 223,209 patients. Overall, females were more likely to develop cADRs to ASMs than males (OR 1.76, 95% confidence interval [CI] 1.55-1.99). The largest differences were observed in patients prescribed lamotrigine (OR 2.17, 95% CI 1.53-3.08, p < 0.001) and carbamazepine (OR 1.63, 95% CI 1.02-2.60, p = 0.042). Also, the OR trended higher for phenytoin (OR 2.46, 95% CI 0.79-7.65, p = 0.12), followed by oxcarbazepine (OR 1.91, 95% CI 0.75-4.85, p = 0.18) and sodium valproate (OR 0.60, 95% CI 0.12-2.99, p = 0.53), but the difference did not reach statistical significance. In the remaining 21 studies, 13 reported numerically higher risk of cADRs among females compared to male patients, and in five of these, the difference was statistically significant.

Conclusion: Our findings confirmed that females are more susceptible to cADRs induced by ASMs than males. More research is needed to understand the pathophysiological mechanisms for this difference.

Protocol registration: PROSPERO (CRD42018111943).

PubMed Disclaimer

References

    1. Auquier-Dunant A, Mockenhaupt M, Naldi L, Correia O, Schröder W, Roujeau J-C. Correlations between clinical patterns and causes of erythema multiforme majus, Stevens–Johnson syndrome, and toxic epidermal necrolysis: results of an international prospective study. Arch Dermatol. 2002;138(8):1019–24. - DOI
    1. Harr T, French LE. Toxic epidermal necrolysis and Stevens–Johnson syndrome. Orphanet J Rare Dis. 2010;5(1):39. - DOI
    1. Mockenhaupt M. Severe cutaneous adverse drug reactions. Braun-Falcós Dermatol. 2009;3:473–84. - DOI
    1. Mockenhaupt M. Epidemiology of cutaneous adverse drug reactions. Allergologie. 2012;35(3):131–44. https://doi.org/10.5414/alx01508 . - DOI
    1. Roujeau JC, Stern RS. Severe adverse cutaneous reactions to drugs. N Engl J Med. 1994;331(19):1272–85. - DOI

Substances

LinkOut - more resources