Baseline Depressive Symptoms as Predictive of Seizure Frequency Reduction among Epilepsy Patients with Partial-Onset Seizures: A Pooled Analysis of Phase III Clinical Trials of Adjunctive Treatment with Eslicarbazepine Acetate (P3.193)

OBJECTIVE: To assess association between baseline depressive symptoms (DS) and seizure frequency reduction (SFR) among subjects with partial-onset seizures. BACKGROUND: Subjects treated with once-daily eslicarbazepine acetate (ESL) 800 mg or 1200 mg as adjunctive therapy had significantly greater SFR versus placebo in three phase III, randomized, double-blind trials. DESIGN/METHODS: Subjects were administered the 10-item interview-based Montgomery-Asberg Depression Rating Scale (MADRS) and self-completed the Quality of Life in Epilepsy Inventory-31, containing the 5-item Emotional Well Being (EWB) subscale. MADRS is scored 0 to 60 with moderate-to-severe DS defined as 蠅20; EWB from 0 to 100 with ≤52 as a commonly-used definition for the presence of DS. Odds ratios (ORs) were examined from two logistic regression models of SFR 蠅50[percnt] (yes/no) including either MADRS or EWB to measure DS (yes/no). Both models included treatment arm, age, race, gender, body mass index, baseline seizure frequency, disease duration, and baseline anti-epileptic drugs (AEDs). Interaction terms were included to examine potential modification of ESL treatment effect by DS and AEDs. RESULTS: Among 1191 of 1214 subjects in the pooled modified intent-to-treat population with complete data, 9.5[percnt] had moderate-to-severe DS by MADRS; 34.3[percnt] had DS by EWB. ESL treatment was associated with greater odds of SFR in both models (1200 mg: OR=2.68/2.64; 800 mg: OR=1.89/1.89, all P P =0.044), but not with EWB (OR=1.18, P =0.311). No modification of ESL treatment effect due to DS ( P 蠅0.27) or baseline AED ( P 蠅0.15) was found in either model. CONCLUSIONS: In this subgroup analysis of the three pooled phase III studies, treatment with ESL was the strongest predictor of SFR. The effect of treatment with ESL was not significantly modified by depressive symptoms or baseline AED. STUDY SUPPORTED BY: Sunovion Pharmaceuticals, Inc. Disclosure: Dr. Bond has received personal compensation for activities with Covance as an employee. Dr. Velez has received personal compensation for activities with Sunovion as an employee. Dr. Anastassopoulos has received personal compensation for activities with Covance as an employee. Dr. Wang has received personal compensation for activities with Covance as an employee. Dr. Cramer has received personal compensation for activities with Bial, Eisai Inc., Sepracor, UCB Pharma, and Sunovion as a consultant. Dr. Cheng has received personal compensation for activities with Sunovian Pharmaceuticals, Inc. Dr. Sousa has received personal compensation for activities with Bial as an employee. Dr. Blum has received personal compensation for activities with Sunovion Pharmaceuticals Inc. as an employee.