Abstracts

Rationale: Eslicarbazepine acetate (ESL) is a once-daily, oral anti-seizure medication (ASM) for focal seizures. In a recently completed real-world, Phase IV study of ESL taken as a first adjunctive therapy with levetiracetam or lamotrigine monotherapy, or as later adjunctive therapy in treatment-resistant patients with focal seizures, psychiatric disorder treatment-emergent adverse events (TEAEs) were reported in 22 of 102 patients in the safety population (21.6%). A history of mood disorders can lead to an increased risk of psychiatric TEAEs with ASM use (Kanner AM. Seizure 2017;49:79–82; Mula M. Curr Treat Options Neurol 2017;19:44). Here, we report a post-hoc analysis of psychiatric-related data from this study.

Methods: This was a multicenter, open-label, non-randomized Phase IV study of adjunctive ESL in patients aged ≥ 18 years with focal seizures in the US and Canada (NCT03116828). The study included two arms: Arm 1 (n = 44: 43% of total study population), where patients received ESL as first adjunctive therapy with levetiracetam or lamotrigine, and Arm 2 (n = 58: 57%), where patients received ESL following current or prior use of adjunctive therapy (64% of patients were taking ≥ 2 ASMs at baseline). The trial comprised screening (1–2 weeks), titration (2 weeks), maintenance (24 weeks), and ESL taper/safety follow-up (4 weeks) periods. Data were collected on TEAEs, medical history of psychiatric disorders, and concomitant psychotropic medications. A Kaplan–Meier time-to-event analysis was performed for the time to first psychiatric disorder TEAE, with hazard ratios (HRs) and 95% confidence intervals (CIs) calculated.

Results: Psychiatric disorder TEAEs occurred in 14% of patients (6/44) in Arm 1 and 28% of patients (16/58) in Arm 2 (Table 1). Overall, the proportions of patients with a history of psychiatric disorders or taking a psychotropic medication were similar between Arms 1 and 2 (Table 1). However, in Arm 1, a history of psychiatric disorders was reported in 83% of patients (5/6) who experienced a psychiatric disorder TEAE versus 42% of patients who did not; a psychotropic medication was taken by 50% (3/6) versus 24% of patients, respectively (Table 1). In Arm 2, a history of psychiatric disorders was reported in 56% of patients (9/16) who experienced a psychiatric TEAE versus 38% of patients who did not; a psychotropic medication was taken by 38% (6/16) versus 19% of patients, respectively (Table 1). The time-to-event analysis for psychiatric disorder TEAEs showed that in Arm 1 psychiatric TEAEs were more likely to appear after the first 4 weeks of treatment, while in Arm 2 events occurred early (Figure 1); however, the differences between arms were not significant (HR: 2.295; 95% CI: 0.898–5.870; p=0.083).

Conclusions: Psychiatric disorder TEAEs were more frequent, and tended to be reported earlier, in patients receiving adjunctive ESL as later therapy for focal seizures compared with patients receiving ESL as the first adjunctive therapy.

Funding: Please list any funding that was received in support of this abstract.: Study funded by Sunovion Pharmaceuticals Inc.