Clin Toxicol (Phila). 2026 Mar 17.
1-14
INTRODUCTION: Lamotrigine is prescribed for neurological and psychiatric conditions, including epilepsy and bipolar disorder. Although generally safe, it may cause rare but severe cutaneous adverse reactions, such as Stevens-Johnson syndrome. This review synthesized case reports and case series on lamotrigine-induced Stevens-Johnson syndrome to improve clinical awareness and promote safer prescribing.
METHODS: PubMed was searched from inception to December 2024 using terms related to lamotrigine and Stevens-Johnson syndrome. Eligible studies were case reports or case series demonstrating Stevens-Johnson syndrome after lamotrigine use. Studies not reporting Stevens-Johnson syndrome, lacking clinical details, or not implicating lamotrigine were excluded. A total of 264 records were identified, and 36 studies met the inclusion criteria. Screening, quality assessment, and data extraction were done independently by two reviewers. Data on demographics, indications for use, lamotrigine dosage, co-administered drugs, clinical features, management, and patient outcomes were extracted and synthesized.
RESULTS: Thirty-six studies comprising 38 individual cases were included. Lamotrigine was used either alone or in combination, most frequently with valproic acid (n = 19). Lamotrigine doses ranged from 12.5 to 750 mg/day, with most cases developing Stevens-Johnson syndrome within the first month of therapy. Clinical features included mucocutaneous lesions, epidermal detachment, and systemic symptoms such as fever and conjunctivitis. Management typically involved immediate lamotrigine discontinuation, corticosteroids, immunoglobulins, and supportive care. Most patients recovered within 2-3 weeks, although two deaths were reported.
DISCUSSION: The findings show that the risk of lamotrigine-induced Stevens-Johnson syndrome is highest in the initial weeks of therapy, especially when lamotrigine is combined with valproic acid or titrated rapidly. Early warning signs such as fever and mucosal symptoms should be closely monitored to ensure timely intervention. Although corticosteroids and immunoglobulins are commonly used, their effectiveness remains uncertain, and supportive care continues to be the cornerstone of management.
CONCLUSION: Lamotrigine-induced Stevens-Johnson syndrome is a rare but serious reaction. Careful dose titration, early recognition of symptoms, and patient education are imperative. Standardized reporting and causality assessment are needed to strengthen the evidence base and support safer prescribing.
Keywords: Lamotrigine; Stevens–Johnson syndrome; adverse drug reactions; cutaneous reactions; systematic review