Lamotrigine Monotherapy in Newly Diagnosed Untreated Epilepsy: A Double-Blind Comparison with Phenytoin
Version of Record online: 5 NOV 2007
Volume 40, Issue 5, pages 601–607, May 1999
How to Cite
Steiner, T. J., Dellaportas, C. I., Findley, L. J., Gross, M., Gibberd, F. B., Perkin, G. D., Park, D. M. and Abbott, R. (1999), Lamotrigine Monotherapy in Newly Diagnosed Untreated Epilepsy: A Double-Blind Comparison with Phenytoin. Epilepsia, 40: 601–607. doi: 10.1111/j.1528-1157.1999.tb05562.x
- Issue online: 5 NOV 2007
- Version of Record online: 5 NOV 2007
- Accepted October 29. 1998.
- Randomised controlled trial
Summary: Purpose: Lamotrigine is an effective add-on therapy against a range of epileptic seizure types. Comparative studies with carbamazepine (CBZ) as monotherapy 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 diagnosed untreated partial seizures or secondarily or primary generalised tonic-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 continued for <48 weeks.
Results: The percentages of patients remaining on each treatment and seizure free during the last 24 and 40 weeks of the study, and times to first seizure 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 discontinuation of 13 (15%) patients from LTG and 18 (19%) from PHT. The adverse-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 nervous system side effects: asthenia, somnolence, and ataxia were each significantly more frequent in the PHT group. The high rate of rash with LTG was probably due to the high starting dose and may be avoidable. A quality-of-life instrument, the SEALS inventory, favoured LTG. Patients taking PHT 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 tolerated, more frequently causing rash, but with a lower incidence of central nervous system side effects.