Abstracts

The objectives of the study were to evaluate the overall effectiveness, safety and tolerability of lamotrigine (LTG) and slow release carbamazepine (CBZ-r) in newly diagnosed elderly epilepsy patients for a 40 week period. The study used a randomised, double-blind, parallell-group design. Patients aged 65 years or older, who had experienced two or more unprovoked seizures (partial seizures, with / without secondary generalisation, or primary generalised tonic/clonic seizures) were included from five European countries. Excluded were subjects previously treated with any antiepileptic drug for more than 2 weeks in the 6 months prior to randomisation. The patients were randomised 1:1 to treatment with LTG or CBZ-r on a b.i.d. schedule. The dose was escalated over 4 weeks and then adjusted based on efficacy and adverse events. The initial, maintenance and maximum daily doses were 25mg, 100mg and 500mg of LTG, and 100mg, 400mg and 2000mg of CBZ-r, respectively. The duration of the maintenance phase was 36 weeks. Of 184 randomised subjects 93 received LTG (46 males=49%) and 91 received CBZ-r (56 males=62%). Mean age was 74.3 years (SD6.2) vs. 73.1 years (SD5.5) in the two treatment groups, respectively. In the LTG group, 68 of 93 subjects completed the study (73%), compared to 61 of 91 (67%) in the CBZ-r group (p=0.33). Time to first seizure was shorter in the LTG group in the Per Protocol analysis set (25% fractile in the survival curve: 8.4 weeks on LTG vs. 19.3 weeks on CBZ-r, p=0.022); however the difference was not significant in the Intention to Treat (ITT) set, using the log-rank test. The proportion of seizure-free subjects in the 4 to 40 week treatment period, not accounting for subjects withdrawn before week 4, were 53 of 87 (61%) on LTG, and 68 of 90 (76%) on CBZ-r (p=0.036). The number of subjects seizure-free from week 20 to week 40, after excluding from the analysis those who withdrew before week 20, was 53 of 75 (71%) for the LTG group and 59 of 69 (86%) for the CBZ group (p=0.032). The number of individuals who experienced adverse events (AE) did not differ in the two groups. The number of AEs leading to stop permanently of the treatment was 23 (25%) on CBZ-r compared to 13 (14%) on LTG. There was no difference in AEs being judged to be related to the study drug by the investigator. With the treatment schedules investigated in this study, CBZ-r produced greater seizure-freedom rates, whereas LTG tended to be associated with lesser AE-related withdrawals. Retention on treatment was comparable in the two groups. (Supported by GlaxoSmithKline (LAM 40089).)