Abstracts

Rationale: Individuals with partial epilepsy commonly report problems with memory. However, no current pharmacological treatment exists for memory problems in epilepsy. Cholinesterase inhibitors have been demonstrated to be effective in treating memory loss in other neurological conditions. We investigated safety and efficacy of the cholinesterase inhibitor galantamine for memory difficulties in partial epilepsy.Methods: 32 patients with partial epilepsy were initially enrolled and 28 completed the study. Participants were randomly assigned to galantamine (n = 17) or placebo (n = 15) and followed for 12 weeks. The galantamine group received either 4mg, 8mg or 12 mg doses. Participants underwent neuropsychological testing of verbal (Selective Reminding) and visual memory (7/24 Spatial Recall) at first study visit and at 12 weeks. Participants returned for six clinical visits during the study to monitor for adverse events (AEs), including seizure frequency. Results: Analysis of the frequency of reported AEs demonstrated that there was a trend for more AEs to be reported at the first initial visit (2 weeks after initiation of treatment) by participants in the placebo group compared to the galantamine group (p = .064), but no trends were noted in AE frequency by the fourth follow-up visit (12 weeks after initiation) (p = .201)(Table 1). The most frequently reported AEs were headache and appetite suppression. The majority of the AEs reported were rated by participants as mild to moderate in severity. Seizure frequency generally did not differ between the groups and did not increase > 50% over baseline rates. However, one of the participants on galantamine experienced an increase in seizure frequency during the study, although this was possibly related to a suspected recurrence of a brain neoplasm. At baseline, no significant group differences were observed on performance of the two memory measures (Table 2). Examination of data revealed no differences in performance of participants receiving galantamine at the three study doses, such that this data was subsequently combined. Follow-up analysis employed a mixed-factors ANOVA design with group (galantamine vs. placebo) and time (baseline, follow-up) as factors. There were no significant main effects for time (p’s > .10) nor were there time by group interactions (p’s > .10), suggesting no improvements in memory in persons taking galantamine.Conclusions: This study appears to suggest that galantamine is generally well-tolerated and safe for use in epilepsy patients with memory problems, with no significant increases in seizure frequency observed with use of galantamine up to 12 mg dose. Disappointingly, no significant changes were observed in memory performance of participants taking galantamine as opposed to placebo. However the efficacy of galantamine cannot be conclusively determined due to the small sample size of this study. Further studies with larger samples and multiple medications (e.g. donepezil, galantamine, rivastigmine) would likely be useful to further evaluate the benefit of cholinesterase inhibitor use of patients with epilepsy.