STEVENS JOHNSON SYNDROME and toxic epidermal necrolysis occurred most frequently following initiation of lamotrigine, according to a nationwide cohort study that quantified the 90-day absolute risk across 25 antiseizure medications and compared medication specific risks with the background risk in the general population.
Researchers analysed nationwide registry data from all Danish residents who initiated an antiseizure medication between 1995 and 2024. The study included 1,388,397 treatment initiations, with a median age of 55.3 years (interquartile range: 40.2–69.9), and 56% of initiators were female. Incident cases of Stevens Johnson syndrome and toxic epidermal necrolysis occurring within 90 days of treatment initiation were identified through national registries. The investigators calculated absolute risks for each medication as cases per 100,000 initiators with 95% confidence intervals and estimated the corresponding 90 day background risk in the general population.
Within 90 days of treatment initiation, 83 cases of Stevens Johnson syndrome or toxic epidermal necrolysis were identified, with most occurring during the first weeks after starting treatment. One year mortality among affected individuals was 17%. These 83 cases accounted for 7% of all incident Stevens Johnson syndrome and toxic epidermal necrolysis cases recorded in Denmark during the study period.
The highest absolute risk was observed following lamotrigine initiation at: 29.31 per 100,000 initiators; 95% confidence interval: 21.46–39.09. Carbamazepine showed the second highest risk at: 16.66 per 100,000 initiators; 95% confidence interval: 8.32–29.80, followed by phenobarbital at: 15.84 per 100,000 initiators; 95% confidence interval: 5.14–36.96. Oxcarbazepine and valproic acid were also associated with elevated absolute risks. Lower risks were reported for pregabalin at: 2.26 per 100,000 initiators; 95% confidence interval: 0.83–4.92, and gabapentin at: 1.24 per 100,000 initiators; 95% confidence interval: 0.50–2.56. No cases were observed for several newer antiseizure medications, although the researchers noted that limited exposure prevented definitive conclusions for some agents. The estimated background risk in the general population was: 0.17 per 100,000 individuals; 95% confidence interval: 0.16–0.18.
The findings provide updated population-based estimates of Stevens Johnson syndrome and toxic epidermal necrolysis risk following antiseizure medication initiation in routine clinical care. By placing medication specific risks alongside the background incidence in the general population, the study offers contemporary data that may assist clinicians when discussing treatment related risks with patients.
The researchers concluded that these updated absolute risk estimates extend previous evidence and may support risk communication during antiseizure medication initiation, while also providing a contemporary reference for both established and newer therapies.
Reference
Heerfordt IM et al. Risk of Stevens-Johnson syndrome and toxic epidermal necrolysis after initiation of antiseizure medication: a Danish nationwide cohort study. Neurology. 2026;107(3):e218355.
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