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From the Department of Medical Genetics (Drs. Kremer, Almqvist, Mezei, and Hayden, and M.A. Hardy), Centre for Molecular Medicine and Therapeutics; the Departments of Psychiatry (Drs. Clark and Raymond) and Psychology (Dr. Graf and C. Jacova) and the Division of Neurology (Drs. Mezei and Snow), University of British Columbia, Vancouver, British Columbia, Canada; the Department of Neurology (Dr. Kremer), University of Nijmegen, the Netherlands; the Department of Neurology/Neurophysiology (Dr. Snow), Auckland Hospital, Auckland, New Zealand; and the Department of Medicine (Neurology) (Dr. Martin), University of Alberta, Edmonton, Alberta, Canada.
Address correspondence and reprint requests to Dr. Michael R. Hayden, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Room 3026—950 West 28th Avenue, Vancouver, British Columbia, V5Z 4H4 Canada.
OBJECTIVE: To assess the efficacy of lamotrigine, a novel antiepileptic drug that inhibits glutamate release, to retard disease progression in Huntington disease (HD).
BACKGROUND: Excitatory amino acids may cause selective neuronal death in HD, and lamotrigine may inhibit glutamate release in vivo.
METHODS: A double-blinded, placebo-controlled study was conducted of 64 patients with motor signs of less than 5 years’ duration who were randomly assigned to either placebo or lamotrigine and assessed at 0 (baseline), 12, 24, and 30 months. The primary response variable was total functional capacity (TFC) score. Secondary response variables included the quantified neurological examination and a set of cognitive and motor tests. Repeated fluorodeoxyglucose 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 secondary response variables differed significantly between the treatment groups. 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 detected.
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 versus 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 disease progression, including motor tests and PET studies, that were sensitive to deterioration over time.
Key words: Huntington disease—Lamotrigine—Drug trial—Indices of progression—PET.
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