Rechallenge with lamotrigine after a rash: a prospective case series and review of the literature.

Objective: To investigate the safety of rechallenge with lamotrigine after an initial rash in patients with refractory bipolar depression.

Design: 1) Prospective, open-label case series in a private practice setting. Patients who developed an initial rash on lamotrigine and were refractory to other treatments were offered rechallenge with the drug using very-low-dose titration (5mg every other day or daily for 14 days, then raised every 14 days by daily-dose increments of 5mg; after 25mg/day the titration proceeded according to the manufacturer's guidelines); and 2) A meta-analysis of prior reports of rechallenge with lamotrigine was conducted.

Measures: A rating scale for rash severity was developed for this study.

Results: Of 27 patients rechallenged with lamotrigine, five required discontinuation due to rash or inflammation. Two of these were potentially serious and all resolved with discontinuation of lamotrigine. Review of the literature identified 48 cases of lamotrigine rechallenge with a success rate of 87 percent; in pooled analysis with the current study the success rate was 85 percent. No patients developed Stevens-Johnson syndrome or toxic epidermal necrolysis after rechallenge. The rate of rash was elevated when rechallenge began within four weeks of the initial rash (36% vs. 7%, p=0.002) and reduced when the initial rash had no signs of potential seriousness (0% vs. 23%, p=0.01).

Conclusions: Rechallenge is a viable option after a benign rash on lamotrigine and can be undertaken with more caution after rashes with 1 to 2 signs of potential seriousness. For rashes with three or more signs of seriousness, rechallenge is not well-studied and may carry significant risk. Rechallenge should be avoided within four weeks of the initial rash.