Abstracts

RATIONALE: The prevalence of epilepsy increases in older age groups, and senior adults comprise an enlarging proportion of the US and world populations. However, very little is known about the tolerability of most antiepileptic drugs in seniors. METHODS: We used a prospective, randomized, double-blind crossover trial to study the tolerability of lamotrigine (LTG) and carbamazepine (CBZ) in senior adults. A 7 week titration period allowed slow initiation of CBZ to a target dose of 800mg (subjects could stop at 600mg if side effects occurred) and a target LTG dose of 300mg. The maintenance treatment period was 4 weeks. Treatment periods were separated by a 4 week washout phase. Mood and cognitive assessments were performed at baseline, the end of each treatment period, and 4 weeks after the final treatment phase. RESULTS: 50 subjects enrolled in the study after informed consent. The mean age was 68.4 years (range 60-80). Mean serum concentration was 5.7?g/ml for CBZ and 4.2?g/ml for LTG. Signicantly more subjects withdrew from the study on CBZ (n=18) than LTG (n=9)(p<0.05). Somnolence was the most frequent cause of withdrawal from the study on CBZ. Somnolence, unsteadiness, and nausea were significantly more frequent with CBZ than LTG. No side effect was reported significantly more frequently on LTG than CBZ. Rash occurred in 6 subjects on CBZ and 3 on LTG. 5 of the 6 Profile of Mood States (POMS) scales and the summary scale scores favored LTG (sign test p<0.05), with the vigor scale difference reaching statistical significance (p<0.01). No differences were found in between-group cognitive test scores, however, the significantly higher rate of withdrawal from CBZ precluded adequate power to determine results with less than a very large difference between mean cognitive test scores as significant. CONCLUSIONS: Even employing slow titration rates, CBZ was not as well tolerated as LTG in senior adults. The pattern of POMS scale scores favored LTG, with the POMS vigor score significantly better on LTG compared to CBZ. Interpretation of cognitive testing results is probematic when a large proportion of subjects from 1 treatment group withdraw prematurely due to adverse CNS effects of the medication.