Abstracts

Rationale: Use of antiepileptic drugs (AEDs) carries a risk of adverse psychiatric effects, including hyperactivity, agitation, irritability, aggression, depression, and psychosis. Approximately 15-20% of patients are affected, although the risk varies considerably between drug classes (Perucca and Gilliam, Lancet Neurol 2012;11:792-802). Eslicarbazepine acetate (ESL) is a once-daily (QD) oral AED that has 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]). This post-hoc analysis of 3 double-blind, placebo (PBO)-controlled trials in patients with POS was conducted to determine the frequency of psychiatric treatment-emergent adverse events (TEAEs) associated with ESL treatment. Methods: The patients were adults (16-75 yrs old) with ≥4 POS/month, receiving 1-3 AEDs, and treated with PBO or ESL 400mg (2 of 3 trials), 800mg, or 1200mg QD for 12 wks (following a 2-wk titration). Patients with TEAEs related to psychiatric disorders were identified from the safety population (TEAEs were categorized using the Medical Dictionary for Regulatory Activities, v13.1). Psychiatric TEAEs included signs and symptoms from the clinical database, and were also identified by clinical audit and data review. TEAEs were evaluated for the double-blind treatment period. Suicidality was assessed retrospectively by blinded review of TEAEs using the Columbia-Classification Algorithm of Suicide Assessment (C-CASA), or prospectively using the Columbia-Suicide Severity Rating Scale (C-SSRS; in 1 study). Patients with a C-CASA code of 1-4 or 7 and/or C-SSRS scores for ‘any suicidal behavior' or ‘worsening in suicidal ideation' post-baseline were classed as having suicidal ideation or behavior. Results: Among the analysis population (n=1447), approximately 80% of patients were Caucasian, and ~30% were taking a single AED. For each of the ESL dose groups, the overall incidence of psychiatric TEAEs was similar to that for placebo (Table 1); there was no clear or consistent relationship between ESL dose and the incidence of psychiatric TEAEs. The most frequently reported psychiatric TEAEs with ESL (any dose) were depression, insomnia, anxiety and memory impairment (Table 1). There were single reports of depression, nervousness, psychotic disorder (all with ESL 400 mg) and attempted suicide (with ESL 800 mg) classifed as serious TEAEs. Severe psychiatric TEAEs were reported in 0.2% of PBO-treated and 0.5% of ESL-treated patients. Conclusions: In patients with POS, psychiatric TEAEs were reported infrequently during treatment with adjunctive ESL. The overall incidence of depression or suicidality TEAEs appeared to be dose-dependent. However, the overall incidence of psychiatric TEAEs was not higher at higher ESL doses.