Lamotrigine-associated rash: risk/benefit considerations in adults and children.

PURPOSE: Lamotrigine (LTG) is an antiepileptic drug (AED) recently released in several countries. It is effective for a variety of seizure types in adults and children both as an add-on agent and in monotherapy, and is generally well tolerated. This report reviews the apparent risk factors for rash associated with LTG to determine whether and how the risk of serious rash can be minimized in practice. METHODS: The panel of experts reviewed all published and unpublished data related to the incidence and risk factors for serious rash with LTG. RESULTS: An allergic skin reaction occurs in approximately 10% of patients, usually in the first 8 weeks. Rashes leading to hospitalization, including Stevens-Johnson syndrome and hypersensitivity syndrome, occurred in approximately one of 300 adults and one of 100 children in clinical trials and appeared to be increased with overrapid titration when starting therapy and with concurrent valproate (VPA). CONCLUSIONS: Recommendations are made for both minimizing the likelihood of serious rash and for management of rash in patients taking LTG. Risk of serious rash may possibly be lessened by strict adherence to manufacturer's dosing guidelines, particularly in patients who are at higher risk: those on concurrent VPA and in the pediatric population.

Weight gain in epileptic patients during treatment with valproic acid: a retrospective study.

BACKGROUND: Weight gain has been recognized as a common adverse effect of valproic acid (VPA) that leads to discontinuation in some patients but its incidence and correlates have been rarely studied. METHODS: We have analyzed the records retrospectively and interviewed 70 adult patients attending an epilepsy clinic on VPA mono- or polytherapy followed over a median of 27 months (range 3-189), as well as 20 patients on carbamazepine (CBZ) monotherapy. Patients were divided into non-weight gainers (< 5% baseline body weight), mild-moderate weight gainers (5-10% body weight) and marked weight gainers (> 10% body weight). The following variables were statistically analyzed to determine their relationship to weight gain: gender, age, body mass index, drug dose, personal or family history of obesity and monotherapy versus polytherapy. RESULTS: Seventy-one percent of the VPA group were weight gainers versus 43% in the CBZ group. A weight gain of more than 4 kg in 70% of the VPA group was observed. The weight gain was often sustained and frequently socially significant to the patients. Patients below or within normal range body mass index prior to the start of VPA experienced the most severe percentage weight gain. From the structured patient interviews, patients with no personal history of weight problems experienced the greatest initial weight increase. CONCLUSION: Strategies should be devised to help patients avoid weight gain when starting on VPA, especially if they are not already overweight.

Clobazam in long-term epilepsy treatment: sustained responders versus those developing tolerance.

Clobazam (CLB) is a structurally unique benzodiazepine (BZD) that has anticonvulsant activity in all types of refractory seizures. The main drawback to CLB, as to other BZDs, is the occurrence of tolerance. To date, there has been no way to predict which patients will develop tolerance. We compared clinical features and treatment variables between two groups of patients whose seizures were initially well controlled with CLB: patients with a sustained response and patients who developed tolerance. We retrospectively identified a group of 50 very good responders from among 173 consecutive patients with uncontrolled epilepsy treated with CLB. Very good responders were defined as patients with > 75% reduction in seizures after the addition of CLB who continued CLB treatment for at least 1 month. At a mean follow-up of 37.5 +/- 12.8 months, 25 patients continued to respond and 25 developed tolerance (mean follow-up 17.0 +/- 15.7 months). Tolerance was defined as a relapse to a level > or = 50% of pre-CLB seizure frequency after an initial very good response for a minimum period of 1 month, despite constant CLB dose and, when available, serum levels. There was no change in concomitant medication. Significant differences were noted between the two groups. The sustained response group had a shorter duration of epilepsy (mean 16.5 vs. 24.5 years, p = 0.015), a greater proportion of individuals with a known etiology for their epilepsy (48 vs. 16%, p = 0.006), and higher CLB levels (0.50 vs. 0.22 microM, p = 0.017), but no significant difference in N-desmethyl-CLB levels.(ABSTRACT TRUNCATED AT 250 WORDS)