Abstracts

Rationale: Several commonly used antiepileptic drugs (AEDs) can impede cognitive function; potential manifestations include impairment of learning in children, driving ability in adults, and memory in elderly patients (Aldenkamp et al, Epilepsia 2003;44[Suppl.4]:21-9). Eslicarbazepine acetate (ESL) is a once-daily (QD) oral AED that has previously been demonstrated to be generally well tolerated as adjunctive therapy in patients with partial-onset seizures (POS) (Rogin et al. Epilepsy Curr 2014;14 [Suppl. 1]). The current post-hoc analysis of 8 double-blind placebo (PBO)-controlled trials (3 phase III epilepsy trials and 5 phase II trials in patients with other conditions) was conducted to determine the frequency of treatment-emergent adverse events (TEAEs) potentially related to changes in cognitive function (‘cognitive TEAEs') during use of ESL. Methods: Patients in the epilepsy trials were adults with ≥4 POS/month, receiving 1-3 AEDs; they were treated with PBO or ESL 400mg (2 of 3 trials), 800mg, or 1200mg QD for 12 wks (following a 2-wk titration). In the phase II trials, patients with bipolar disorder, post-herpetic neuralgia, migraine, or fibromyalgia received ESL (400-2400mg/day) or PBO for up to 16 weeks. Patients with TEAEs related to cognitive function were identified from the safety population (TEAEs were categorized using the Medical Dictionary for Regulatory Activities, v13.1). Cognitive TEAEs included signs and symptoms from the clinical database and were also identified by clinical audit and data review. Results: The analysis population for the epilepsy trials consisted of 1447 patients (~80% Caucasian; ~30% taking a single AED; median daily ESL dose = 752mg; median duration of treatment = 98 days) whereas that for the ‘non-epilepsy' trials comprised 1705 patients (median daily ESL dose = 755mg; median duration of treatment = 64 days). Incidences of cognitive TEAEs are shown in Table 1. In the epilepsy population, the incidences of memory impairment and attention disturbance were slightly higher at higher ESL doses. There were 2 reports of visual hallucinations in patients taking placebo (phase III studies), and 2 reports of ‘psychotic disorder' in patients taking ESL (1 phase III recipient of ESL 400mg; 1 phase II recipient of ESL ≥1400mg). Attention disturbance led to discontinuation in 3 phase III patients (1 each taking PBO, ESL 800mg and ESL 1200mg). Five other phase III patients discontinued, due to amnesia (n=2, ESL 800mg, ESL1200mg), aphasia (n=2, ESL 1200mg) and cognitive disorder (n=1, ESL 1200mg). Conclusions: Cognitive TEAEs were reported infrequently (each ≤1.5% of patients) during treatment with adjunctive ESL, although all patients were taking other concomitant AEDs, many of which are associated with impairments of cognitive function. The most frequently reported cognitive TEAEs were irritability, memory impairment and attention disturbance (all reported more frequently with ESL vs PBO). For the vast majority of cognitive TEAEs, the incidence was low in patients taking ESL (each ≤0.7%).