Abstracts

Rationale: In 2000, 332 (20.5%) of 1617 seizure-free patients attending clinics at the Epilepsy Unit in the Western Infirmary, were completely controlled on antiepileptic drug (AED) polytherapy for at least the previous year1. Since then, 6 new AEDs have been licensed in Europe for the adjunctive treatment of epilepsy. We, therefore, decided to repeat the analysis to re-explore the likely impact of the increasing range of newer agents on clinical outcomes. Methods: The database of all treated patients registered with the Epilepsy Unit between 1982 and 2008 was interrogated. Data from patients seizure-free for at least the previous year on AED polytherapy were examined. Results: In the latest analysis, of 2379 seizure-free patients, 20.4% (n=486 - 254 women, 232 men, aged 18-95 years [median age 49 years]) were on combination therapy. The majority achieved control on their first or second combination regimen (n=283, 58.2%), with the remainder having already failed two (n=88, 18.1%), three (n=64, 13.2%), four (n=24, 4.9%), or more (n=27, 5.6%) drug schedules. Comparisons with the original analysis can be seen in Table 1. Two AEDs were taken by 395 (81.3%) patients in 2010, and by 287 (86.4%) in 2000. There were 64 effective duotherapy regimens, sodium valproate with lamotrigine being the commonest successful pairing (n=96, 24.3%) (Table 2). Mean daily doses were lower (sodium valproate 1200mg, lamotrigine 155mg) compared with when sodium valproate was taken with carbamazepine or levetiracetam (n=42; 1621mg; p<0.001), and lamotrigine was combined with topiramate or levetiracetam (n=33; 430mg; p<0.001), supporting previous evidence of synergism2,3. In the recent analysis, a higher percentage of patients were seizure-free on 3 (n=85, 17.5% in 2010; n=42, 12.7% in 2000), as opposed to 2 AEDs (n=395, 81.3% in 2010; n=287, 86.4% in 2000). Only 0.9% of patients in 2000, and 1.2% in 2010 required 4 AEDs. Sodium valproate, lamotrigine, and carbamazepine were most frequently used, accounting for over 50% of prescribing. In these combinations, newer AED utilization increased from 28.4% in 2000 to 44.1% in 2010, with levetiracetam (n=109, 10.2%) and topiramate (n=81, 7.6%) most commonly employed in the later analysis. Conclusions: These results imply that patients taking AED polytherapy regimens are more likely to have improved outcomes with drug substitution rather than addition. In the last decade, when used as adjunctive therapies, new agents have not impacted importantly on seizure outcomes. An alternative approach to AED development may be required to change this disappointing situation.