Antiepileptic Drugs Major Contributors to Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis globally: JAMA

A new study published in the Journal of American Medical Association showed that antiepileptic medications are a leading cause of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) globally, and where clinically suitable, nonaromatic antiepileptic alternatives should be used preferentially to lower this serious risk.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), the most severe form of drug hypersensitivity response with a 50% fatality rate, are often linked to antiepileptic medications (AEDs). Nevertheless, there hasn't been a thorough analysis of the total percentage of these instances linked to AEDs. Thus, the purpose of this study was to assess the percentage of AED-associated SJS/TEN.

From the beginning until March 17, 2026, the MEDLINE and Embase databases were searched; only English-language papers and human subjects were included in the findings. Included were all observational and experimental studies that documented SJS/TEN triggers at the patient level. Using a predetermined template, two reviewers independently reviewed studies and retrieved data. A random-effects meta-analysis was used to calculate the pooled proportions with 95% CIs in order to assess the proportion of AED-associated SJS/TEN. To investigate heterogeneity, subgroup analyses by age group (children vs. adults) and geographic area were carried out.

50 studies with 4403 patients that identified SJS/TEN triggers at the patient level were included in this systematic review and meta-analysis. 88% (95% CI, 83-92) of the instances had single-drug triggers.

AEDs were responsible for 23% (95% CI, 19–26) of the total number of SJS/TEN cases. Aromatic AEDs accounted for nearly all AED-associated cases (96%; 95% CI, 92-99), most often carbamazepine (39%; 95% CI, 29-50), phenytoin (19%; 95% CI, 11-28), and lamotrigine (15%; 95% CI, 8-22). Rarely were nonaromatic AEDs involved (2%; 95% CI, 0-4).

The percentage of AED-associated SJS/TEN varied significantly by region, from 42% (95% CI, 26-59) in West Asia to 10% (95% CI, 0-33) in Africa. Compared to adults, children had a much greater percentage of AED-associated SJS/TEN cases.

Overall, roughly 25% of SJS/TEN cases reported globally were linked to AEDs. Carbamazepine, phenytoin, and lamotrigine were the most often implicated aromatic compounds in nearly all AED-associated cases. These results support the preferential use of nonaromatic AEDs, particularly in high-risk patients and when clinically appropriate, and point to aromatic AEDs as the primary causes of SJS/TEN.

Source:

Lee, E. Y., Knox, C., Sugumar, C., & Phillips, E. J. (2026). Proportion of antiepileptic drug-associated Stevens-Johnson syndrome and toxic epidermal necrolysis: A meta-analysis: A meta-analysis. JAMA Dermatology (Chicago, Ill.). https://doi.org/10.1001/jamadermatol.2026.2473