Lamotrigine monotherapy in newly diagnosed untreated epilepsy: A double-blind comparison with phenytoin

Purpose: Lamotrigine is an effective add-on therapy against a range of epil eptic seizure types. Comparative studies with carbamazepine (CBZ) as monoth erapy in newly diagnosed epilepsy suggest similar efficacy. In this study, lamotrigine (LTG) and phenytoin (PHT) are compared. Methods: In a double-blind parallel-groups study, 181 patients with newly d iagnosed untreated partial seizures or secondarily or primary generalised t onic-clonic seizures were randomised to two treatment groups. One group (n = 86) received LTG titrated over 6 weeks from a starting dose of 100 mg/day . The other (n = 95) received PHT titrated from 200 mg/day. Treatment conti nued for less than or equal to 48 weeks. Results: The percentages of patients remaining on each treat ment and seizu re free during the last 24 and 40 weeks of the study, and times to first se izure after the first 6 weeks of treatment (dose-titration period), did not differ significantly between the treatment groups. These were measures of efficacy. Time to discontinuation, a composite index of efficacy and safety , likewise did not distinguish between treatments. Adverse events led to di scontinuation of 13 (15%) patients from LTG and 18 (19%) from PHT. The adve rse-event profile for LTG was dominated by skin rash [discontinuation of 10 (11.6%) patients compared with five (5.3%) from PHT] rather than central n ervous system side effects: asthenia, somnolence, and ataxia were each sign ificantly more frequent in the PHT group. The high rate of rash with LTG wa s probably due to the high starting dose and may be avoidable. A quality-of -life instrument, the SEALS inventory, favoured LTG. Patients taking PI-IT showed the biochemical changes expected of an enzyme inducing drug, whereas those taking LTG did not. Conclusions: LTG and PHT monotherapy were similarly effective against these seizure types in patients with newly diagnosed epilepsy. LTG was better to lerated, more frequently causing rash, but with a lower incidence of centra l nervous system side effects.