Influence of lamotrigine on progression of early Huntington disease - A randomized clinical trial

Objective: To assess the efficacy of lamotrigine, a novel antiepileptic dru g that inhibits glutamate release, to retard disease progression in Hunting ton disease (HD). Background: Excitatory amino acids may cause selective ne uronal death in HD, and lamotrigine may inhibit glutamate release in vivo. Methods: A double-blinded, placebo-controlled study was conducted of 64 pat ients with motor signs of less than 5 years' duration who were randomly ass igned to either placebo or lamotrigine and assessed at 0 (baseline), 12, 24 , and 30 months. The primary response variable was total functional capacit y (TFC) score. Secondary response variables included the quantified neurolo gical examination and a set of cognitive and motor tests. Repeated fluorode oxyglucose measurements of regional cerebral metabolism using PET also were included. Results: Fifty-five patients (28 on lamotrigine, 27 on placebo) completed the study. Neither the primary response variable nor any of the s econdary response variables differed significantly between the treatment gr oups. Both the lamotrigine and the placebo group deteriorated significantly on the TFC, in the lamotrigine group by 1.89 and the placebo group by 2.11 points. No effect of CAG size on the rate of deterioration could be detect ed. Conclusions: There was no clear evidence that lamotrigine retarded the progression of early Huntington disease over a period of 30 months. However , more patients on lamotrigine reported symptomatic improvement (53.6 versu s 14.8%; p = 0.006), and a trend toward decreased chorea was evident in the treated group (p = 0.08). The study also identified various indices of dis ease progression, including motor tests and PET studies, that were sensitiv e to deterioration over time.