Abstracts

Rationale: Eslicarbazepine acetate (ESL) is a once-daily (QD), oral antiepileptic drug (AED) for focal (partial-onset) seizures. Here, we evaluate the occurrence of psychiatric adverse events (AEs) in clinical trials of ESL in adults with focal seizures, analyzed according to psychiatric history and current symptom status. Methods: This post-hoc analysis evaluated data pooled from three Phase III, randomized, double-blind, placebo-controlled trials (BIA-2093-301, -302, -304). After an 8-week baseline period, adults with >=4 focal seizures/month and taking 1-3 AEDs were randomized equally to receive placebo, ESL 400 mg (not reported here), 800 mg, or 1200 mg QD (up to 2-week titration; 12-week maintenance). Incidences of psychiatric treatment-emergent AEs (TEAEs) were evaluated according to psychiatric history and current symptom status; patients were categorized on the basis of three separate criteria: medical history of psychiatric disorders (yes/no); Montgomery-Åsberg Depression Rating Scale (MADRS) score at baseline (0-6: normal; 7-19: mild depression; 20-34: moderate depression); use of concomitant psychotropic drugs (yes/no). Results: The safety population comprised 1447 patients. In all treatment groups (placebo and both ESL dose groups), the overall frequency of psychiatric TEAEs, as well as the frequencies of anxiety and depression, were higher in patients with a medical history of psychiatric disorders than in those with no such history (Table 1). Furthermore, the overall frequency of psychiatric TEAEs, as well as the frequency of depression, were higher in patients using concomitant psychotropic drugs than in those not using psychotropic drugs, in all treatment groups (Table 1). Finally, in the subgroups categorized using baseline MADRS score, the overall frequency of psychiatric TEAEs was greater in patients with mild or moderate depression at baseline, than in those categorized as 'normal' at baseline, across all treatment groups (Table 2).  Conclusions: In clinical trials of ESL in adults with focal seizures, psychiatric adverse events generally occurred more frequently in patients with current psychiatric symptoms or a history of psychiatric disorders, with no marked differences between the placebo and ESL treatment groups. Funding: Studies funded by BIAL; Study 304 and analyses funded by Sunovion Pharmaceuticals Inc.