Abstracts

Rationale: Most antiepileptic drugs (AEDs) are associated with the occurrence of treatment emergent adverse events (TEAEs); of these, psychiatric TEAEs are often overlooked, but are still a significant consideration. Eslicarbazepine acetate (ESL) is a once-daily oral AED, demonstrated to be generally well tolerated in the treatment of partial-onset (focal) seizures (POS). In a previous analysis of adjunctive ESL, psychiatric TEAEs were reported infrequently. This post-hoc analysis examines the frequency of psychiatric TEAEs in two conversion to ESL monotherapy trials. Methods: This is a post-hoc analysis of data pooled from two Phase III, randomized, dose-blind conversion to ESL monotherapy trials (093-045 and -046) in adults (16–70 years) with POS, uncontrolled by one or two AEDs. Following a baseline period (8-weeks), eligible patients were randomized 2:1 to receive ESL 1,600 mg or 1,200 mg once-daily for 18 weeks (2-week titration, 6-week baseline AED taper, 10-week monotherapy). The pooled intent-to-treat (ITT) population (all patients receiving ≥1 dose of ESL) was used for all analyses. Psychiatric TEAEs and serious psychiatric AEs (SAEs) (categorized using the Medical Dictionary for Regulatory Activities, v13.1) were identified. Depression and suicidality TEAEs were also identified. Suicidality was assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS). Results: The pooled ITT population comprised 365 patients (ESL 1,600 mg, n = 242; ESL 1,200 mg, n = 123). The incidence of psychiatric TEAEs was similar between dose groups (ESL 1,600 mg, 15.3%; ESL 1,200 mg, 17.9%) (Table 1). Insomnia, anxiety, confusional state, depression, and stress were the most frequently reported psychiatric TEAEs. All other psychiatric TEAEs occurred in < 1% of patients. Overall, psychiatric AEs were infrequent during baseline ( < 2.5% of patients). In the ESL 1,600 mg group, SAEs (anxiety and depression) occurred in one patient (0.4%) and psychiatric TEAEs led to discontinuation in six patients (2.5%); of these, depression (1.2%) and anxiety (0.8%) were the most frequent. No SAEs or TEAEs leading to discontinuation occurred in the ESL 1,200 mg group. Overall, the majority of reported psychiatric TEAEs were mild (57.6%) or moderate (35.6%) in severity. TEAEs related to depression and suicidality were reported more frequently in the ESL 1,200 mg group (8.9%) than in the ESL 1,600 mg (5.0%) group (Table 2). According to C-SSRS ratings, suicidal ideation or behavior appeared to be more frequent in the ESL 1,200 mg group (4.1%), than in the 1,600 mg group (1.2%) (Table 2). Conclusions: Psychiatric TEAEs were reported in < 17% of patients in Phase III conversion to ESL monotherapy trials. Incidences were similar between dose groups and the majority of TEAEs were mild or moderate in severity. The incidence of depression and suicidality TEAEs, as well as C-SSRS ratings of suicidal ideation or behavior, were low and did not appear to be related to ESL dose. Funding: Studies sponsored by Sunovion Pharmaceuticals Inc.