Lamotrigine in multihandicapped therapy-resistant epileptic patients

This study evaluated the effects of lamotrigine in routine therapy in the highly selected clientele of the Residential Department of the Bethel Epilepsy Centre.

In an open, observational, add-on study design, 125 resident patients with severe therapy-resistant epilepsy and multiple additional handicaps were treated with lamotrigine in titrated doses. Seizure types, monthly seizure frequency, seizure severity, and psychological status were recorded during a 3-month baseline and a 3-month lamotrigine treatment period prior to the key date of this analysis (31 March 1996).

At the time of analysis, the mean lamotrigine dosage was 391 mg/day (mean serum concentration 4.25 mg/L). 71.4% of the patients (after a mean observation time of 21.9 months) were still receiving lamotrigine. In the remaining 28.6%, the main reasons for withdrawal (after a mean of 10.5 months) were lack of effectiveness (19 patients, 15.2%), increase in seizure frequency (8 patients, 6.4%), and negative psychotropic effects (5 patients, 4.0%). On an intention-to-treat basis, the responder rate (reduction in seizure frequency by 50% or more) was 28.8% (35.6% in focal epilepsy, 26.7% in generalised epilepsy, and 22.4% in epilepsy with focal and generalised seizures). Seizure reduction was similar for all seizure types. Lamotrigine was more effective when combined with valproic acid (p < 0.005) and less effective when combined with carbamazepine or phenytoin. Stepwise multivariate logistic regression revealed valproic acid (and not lamotrigine dose or concentration, co-medication, epileptic syndrome, or seizure type) as the only factor predicting seizure response. 28.0% of the patients had shorter and/or less severe seizures, and 8.8% had longer/more severe seizures. 25.6% experienced a positive and 8.0% a negative psychotropic effect (mostly aggression). In all, 53.6% of patients benefited according to the three efficacy criteria, and 8.8% deteriorated. The most frequent dose-dependent adverse effects were ataxia, dizziness and diplopia.

Lamotrigine was an effective and well tolerated drug for this special patient group, especially when combined with valproic acid.