Monday July 3, 2006 15:00-17:00 Hall 3A Discussion Group Session Cognitive dysfunction in children with temporal lobe epilepsy
Purpose: This study was designed to compare monotherapy with sodium valproate (VPA) and lamotrigine (LTG) in patients with newly diagnosed epilepsy. Method: A total of 226 untreated patients (116 male) with a recent diagnosis of epilepsy (60 idiopathic generalised epilepsy, 149 localisationrelated epilepsy, 17 unclassified) were randomised to receive either VPA or LTG as monotherapy. Median age was 35 years (range 13-80 years). Patients were followed-up at six-weekly intervals and remained in
... e study until reaching a predetermined end point (12 month seizurefreedom; intolerable side-effects including idiosyncratic reaction; lack of efficacy despite adequate dosing). Results: Twenty-nine patients were excluded from the analysis (24 lost to follow-up, 3 withdrawn consent, 1 protocol violator, 1 nonepileptic attack). A total of 197 patients reached an end point, with 126 (63%) becoming seizure-free for a minimum period of 12 months on initial monotherapy. Of these, 64 took VPA (67% of VPA completers; median dose = 1000 mg, range 600-3000 mg) and 62 took LTG (60% of LTG completers; median dose = 200 mg, range 100-700 mg). Thirty-eight patients (24 VPA, 14 LTG) experienced intolerable side effects, while a further 33 (18 VPA, 15 LTG) failed to report acceptable efficacy despite adequate dosing. There were no significant changes in mean (±SEM) serum concentrations of testosterone (p = 0.225), SHBG (p = 0.201), or androstenedione (p = 0.394) in either patient group at 6 months after initiation of therapy. Conclusion: These findings suggest that there is little (if any) difference in the efficacy, tolerability, or hormonal effects of VPA or LTG monotherapy in the treatment of newly diagnosed epilepsy. Purpose: There is a paucity of randomised controlled trials (RCTs) that inform a choice among antiepileptic drugs, and existing trials have largely failed to examine longer term effectiveness. SANAD assesses these longer term outcomes. Method: SANAD is a multicentre, UK based, unblinded RCT recruiting patients over the age of 5 years, requiring antiepileptic drug monotherapy. SANAD has 2 arms. Patients for whom carbamazepine was the standard drug (arm A) were randomised to carbamazepine, gabapentin, lamotrigine, oxcarbazepine or topiramate. Patients for whom valproate was the standard drug (arm B) were randomised to valproate, lamotrigine or topiramate. Recruitment commenced in 1999, ended 2005, and follow up ended in 2005. Outcomes included time to the following events: withdrawal of allocated treatment, 12 month remission from seizures, first seizure, as well as adverse events, quality of life and cost effectiveness. Results: 2443 patients were recruited, for whom we have 7799 patient years follow up, 95% of the maximum possible. 1721 patients entered arm A, 378 were allocated carbamazepine, 377 gabapentin, 378 lamotrigine, 210 oxcarbazepine and 378 topiramate. The mean age was 38.3 yrs, 55% were male and 89% were classified as having a partial epilepsy syndrome. 716 patients entered arm B, 238 were allocated valproate, 239 lamotrigine and 239 topiramate. The mean age was 25.5 yrs, 60% were male, and 62% were classified as having an idiopathic generalised epilepsy syndrome. Full clinical results will be presented. Conclusion: Large multicentre studies examining the longer term effects of antiepileptic drugs, such as SANAD, are required to inform clinical practice. Purpose: To compare lamotrigine (LTG) and slow-release carbamazepine (CBZ) in the treatment of newly diagnosed epilepsy in the elderly. Method: Patients aged >65 years with a history of two or more unprovoked partial and/or tonic-clonic seizures received LTG (n = 93) or CBZ (n = 91) in a randomised double-blind 40-week trial. Target dose was 100 mg/day for LTG and 400 mg/day for CBZ; dose escalation was 4 weeks and dose adjustments according to response were permitted. Results: In the LTG group, 68 patients (73%) completed the trial compared with 61 (67%) in the CBZ group (not significant). Time to withdrawal from any cause did not differ between groups (p = 0.34). The number of subjects who completed the study and were seizure-free during weeks 4-40 was 37 (40%) in the LTG group and 46 (50%) in the CBZ group. Adverse events leading to withdrawal occurred in 26 (28%) CBZ-treated subjects and 15 LTG-treated subjects (16%). The Liverpool Adverse Event Profile (AEP) score showed a non-significant advantage for LTG. Conclusion: LTG and CBZ showed comparable effectiveness, with a trend for higher seizure-free rates for CBZ and better tolerability for LTG. Acknowledgment: Supported by GlaxoSmithKline.