JPERM

Objective: This study was aimed to examine the association between lamotrigine and the risk of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) in patients with bipolar disorder, seizure, and depression. Methods: A nested case-control study was conducted using the Korea national health insurance claims database from 2011 through 2015. We included patients with bipolar disorder, seizure, and depression and each patient's baseline was defined as the date of cohort entry. We identified cases as hospitalized patients with SJS and/or TEN from 2011 to 2015. Up to 20 controls without SJS/TEN and subcutaneous diseases were matched for each case based on age (±3 years), gender, and date of cohort entry (±60 days) by using the incidence-density sampling method. A conditional logistic regression model was used to estimate the risk of SJS/TEN associated with lamotrigine use, simultaneously adjusting for potential confounders. Results: We identified 496 cases and randomly selected 9,920 matched controls. Among cases, those who diagnosed as SJS, TEN, and SJS/TEN overlap was 398 (80.2%), 84 (16.9%), and 14 (2.8%), respectively. Use of lamotrigine significantly increased the risk of SJS/TEN in our study (adjusted odds ratio [OR]=10.93, 95% confidence interval [CI]: 7.48-15.97). The adjusted ORs for SJS/TEN associated with duration of lamotrigine treatment were 23.73 (95% CI: 15.17-37.12) within 30 days, 13.38 (95% CI: 4.39-40.81) in 30-60 days, 0.99 (95% CI: 0.34-2.93) over 60 days, respectively. Conclusion: Our study suggests that lamotrigine is associated with the increased risk of SJS/TEN, especially within 60 days of initiating lamotrigine. (JPERM 2019;11:21-28): Lamotrigine; Stevens-Johnson syndrome; Toxic epidermal necrolyses; Adverse drug reactions

Keywords Lamotrigine, Stevens-Johnson syndrome, Toxic epidermal necrolyses, Adverse drug reactions