We evaluated the efficacy and safety of lamotrigine (300 and 500 mg/day) as add-on therapy in a multicenter, randomized, double-blind, parallel-group, placebo-controlled study of 216 patients with refractory partial seizures. During 6 months of treatment, median seizure frequency decreased by 8% with placebo, 20% with 300 mg lamotrigine, and 36% with 500 mg lamotrigine. Seizure frequency decreased by > or = 50% in one-third of the 500-mg group and one-fifth of the 300-mg group. Reductions in seizure frequency and seizure days were statistically significant, compared with placebo, for the 500-mg group but not the 300-mg group. Most adverse events were minor and resolved over time. Nine percent of patients on lamotrigine withdrew because of adverse experiences. Lamotrigine plasma concentrations appeared to be a linear function of dose, and the drug did not affect plasma concentrations of concomitant antiepileptic drugs. Lamotrigine was safe, effective, and well tolerated as add-on therapy for refractory partial seizures.
We postulate that palatal myoclonus after infarction of the brainstem or cerebellum, or both, is the manifestation of denervation supersensitivity secondary to lesions involving the dentatorubroolivary system. Two cases of our own and 31 from the English and French literature were analyzed in order to determine the delay between the occurrence of presumed anatomical lesions and the recognition of palatal myoclonus. The intervals varied from 2 to 49 months with the median between 10 and 11 months. The natural history of palatal myoclonus following brainstem infarction seemed consistent with the hypothesis.
Summary: Clinical use of the antiepileptic drug (AED) lamotrigine (LTG) has dramatically increased since its introduction in Europe in 1991 and in the United States in 1994. This article surveys the English-language literature of LTG published before 1998. This literature is concerned with the molecular mechanisms of LTG's antiepileptic action, evaluation of its clinical antiepileptic efficacy, adverse experiences associated with its clinical use, and current guidelines for its initiation. LTG's efficacy has been extensively confirmed in multiple postmarketing studies, and its applications are broad. The most serious adverse experiences have involved skin rash. Valproic acid affects LTG metabolism, and a specific set of guidelines for the concurrent use of valproic acid and LTG has been developed. Unique issues are also associated with its pediatric use. LTG has a significant place in clinical management of a wide range of epilepsy syndromes, and the scope of its use is expanding. Accumulating clinical data enable the clinician to maximize its efficacy and minimize adverse experiences. Guidelines for its pediatric use must be followed diligently.
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