Safety, Tolerability and Efficacy of Eslicarbazepine Acetate as Adjunctive Therapy in Patients Aged ≥ 65 Years with Focal Seizures.

backgroundThe incidence of epilepsy is high within the first few years of life, stabilizes over the second through fifth decades, and then rises again. Treatment of elderly patients with antiepileptic drugs (AEDs) is complicated by increased sensitivity to drug effects, altered pharmacokinetics and an increased risk for drug interactions due to polytherapy. On the other hand, the safety and efficacy data of AEDs attained during clinical development programmes are relatively limited for this age group.

objectiveThe aim of this study was to evaluate the safety, tolerability and efficacy of eslicarbazepine acetate (ESL) as adjunctive therapy in patients aged ≥ 65 years with focal-onset seizures (FOS).

methodsThis was an international, multicentre, open-label, non-controlled, single-arm, post-European approval commitment study with flexible doses of ESL between 400 and 1200 mg/day. Seventy-two elderly patients with at least two FOS in the prior 4 weeks, and treated with one or two AEDs, were enrolled. The study consisted of an 8-week baseline, followed by a 26-week treatment period during which the investigator was allowed to up- or down-titrate the ESL dose, and a 4-week follow-up period. Safety and tolerability were assessed as well as mental sedation, cognitive mental state and suicidal ideation. Efficacy was assessed based on patient diaries regarding the absolute and relative changes in seizure frequency, change in intellectual impairment and quality of life.

resultsOverall, 47 (65.3%) patients experienced 152 treatment-emergent adverse events (TEAEs). The most frequent were dizziness (12.5%), somnolence (9.7%), fatigue, convulsion and hyponatraemia (8.3% each). All patients that experienced hyponatraemia (6/72) recovered without sequelae. Three patients died during the study (due to cardiac failure, glioblastoma multiforme and ischaemic stroke, all considered unrelated to ESL). Overall, 16 (22.2%) patients discontinued prematurely due to TEAEs. The incidences of clinically significant findings were low for vital signs, ECG, physical and neurological examinations. No TEAEs of hypothyroidism were reported; however, 24 (33.3%) patients presented post-baseline shifts from normal to decreased free T4 levels (not clinically significant). ESL decreased standardized seizure frequency from a mean of 4.8 seizures at baseline to 3.6 seizures at endpoint (p > 0.05); and mean number of days with seizures significantly decreased from 4.1 (baseline) to 2.8 at endpoint (p = 0.0408).

conclusionESL taken once daily (400-1200 mg) as adjunctive therapy in patients aged ≥ 65 years was found to be safe, well tolerated and efficacious (EudraCT number: 2009-012587-14).