Lamotrigine is a chemically novel antiepileptic drug which has not been adequately assessed for its antineuralgic properties. It was used in a double-blind placebo controlled crossover trial in 14 patients with refractory trigeminal neuralgia. Patients continued to take a steady dose of carbamazepine or phenytoin throughout the trial over a 31-day period. Each arm of the trial lasted 2 weeks with an intervening 3-day washout period. The maintenance dose of lamotrigine was 400 mg. Lamotrigine was superior to placebo (P = 0.011) based on analysis of a composite efficacy index which compared the numbers of patients assigned greater efficacy on lamotrigine with those assigned greater efficacy on placebo. Efficacy for one treatment over another was determined according to a hierarchy of: (i) use of escape medication; (ii) total pain scores; or (iii) global evaluations. Eleven of the 13 patients eligible for inclusion in the composite efficacy index showed better efficacy on lamotrigine compared with placebo. Global evaluations further suggested that patients did better on lamotrigine than placebo (P = 0.025). The adverse reactions with both lamotrigine and placebo were predominantly dose-dependent effects on the central nervous system. A 14th patient withdrew from the study due to severe pain during the placebo arm of the trial. It would appear that lamotrigine has antineuralgic properties.