Lamotrigine rechallenge after a skin rash. A combined study of open cases and a meta-analysis.

OBJECTIVE To determine the safety of lamotrigine rechallenge after a first episode of skin rash in bipolar patients. METHOD An open cases prospective study was conducted with patients who, developed a skin rash when first treated with lamotrigine, were refractory to other treatments, and were offered lamotrigine rechallenge using a different dose titration. Additionally a review was performed on previous skin rash management strategies and lamotrigine rechallenge reports. RESULTS Every 3 out of 10 lamotrigine rechallenge patients required drug interruption due to persistent rash. One of them was potentially serious and resolved by stopping the lamotrigine. The review of available literature identified several lamotrigine rechallenge studies with rates of positive results varying between 70% and 87% depending on the study. No patient developed Stevens-Johnson syndrome or toxic epidermal necrolysis after rechallenge. The rate of rash was higher when rechallenge began between 4 weeks from initial rash (19% vs. 7%, P=.001) and decreased when first rash showed no potentially serious signs (0% vs.19%, P=.01). CONCLUSIONS Rechallenge is a viable option after a benign lamotrigine-induced rash, and can even be rechallenged after rash with greater precautions when there exists one or two potentially serious signs. In cases of more serious rash there are no reliable data available on rechallenge safety and it may pose a significant risk. In those cases rechallenge should better be avoided between 4 weeks from first rash.