Abstracts

Rationale: When a new drug is licensed, the only available information on its use comes from placebo-controlled, dose-ranging, randomized clinical trials. This prospective audit explored outcomes with the recently introduced retigabine (RTG), a novel first-in-class neuronal K+ channel opener, as adjunctive treatment in everyday clinical practice. Methods: After 12 weeks on stable AED dosing, RTG was introduced in a three times daily schedule and titrated as necessary in patients with drug-resistant localization-related epilepsy. Review took place every 6-8 weeks until 1 of 4 end-points was reached: seizure freedom for > 6 months on a given RTG dose; > 50% (responder) or < 50% (marginal benefit) seizure reduction over 6 months compared with baseline on the highest tolerated RTG dose; withdrawal of RTG due to lack of efficacy, side effects or, or both. Results: To date, 31 of 51 recruited patients (23M; 28F, age range 20-67 years [median 45 years]) with uncontrolled partial-onset seizures with or without secondary generalisation (monthly frequency 1-60; [median 3]) have reached an endpoint. They received a median of one (range 1-4) antiepileptic drug (AED), having previously tried 1-14 schedules (median 3). Seizure freedom has been achieved in 3 (9.7%) patients (150mg, 300mg, 600mg RTG daily) so far. All took RTG in combination with lamotrigine. Three (9.7%) other patients could be classified as responders, (600mg, 600mg, 900mg RTG daily) with 11 (35.5%) more demonstrating marginal benefit and remaining on the drug (300 - 1200mg RTG daily). RTG was withdrawn in 14 (28%) patients, all due to side-effects (8 taking 150mg, 3 taking 300mg, 1 taking 450mg, 1 taking 600mg, 1 taking 900mg all in a thrice daily schedule). Problems resulting in drug withdrawal included headache, dizziness, diplopia, ataxia, agitation, sedation, tiredness, depression, parasthaesia and poor sleep pattern. Three of these patients developed urinary hesitancy and/or frequency. There were no differences in mean World Health Organisation Defined Daily Doses (http:/www.whocc.no/atc_ddd_index/.) of adjunctive AEDs in patients reaching a positive endpoint (n=17; 1.97) compared with those not tolerating RTG (n=14; 1.94). Conclusions: Adjunctive RTG was effective and well-tolerated in some patients with drug-resistant localization-related epilepsy. Others discontinued treatment due to a range of side-effects, often at low dosage. These patients did not have a higher baseline drug burden than those tolerating RTG administration. No patients have come off treatment due to lack of efficacy alone at this time.