Abstracts

Rationale: Eslicarbazepine acetate (ESL) is a novel once-daily (QD) anticonvulsant, extensively converted to eslicarbazepine after oral administration, which blocks voltage-gated sodium- and calcium-channels. Depressive disorders are common comorbidities of epilepsy and they have been associated with a poor response to antiepileptic drug therapy. This post-hoc analysis evaluated the efficacy and tolerability of ESL as adjunctive treatment in adult patients with partial-onset seizures (POS) and co-morbid clinically relevant depressive symptoms. Methods: Data from two (BIA-2093-301 and -302) phase III multicentre, double-blind, randomized, placebo-controlled studies in adult patients with ≥4 partial-onset seizures per 4 weeks despite treatment with 1-3 AEDs was pooled and analysed. ESL was administered at QD doses of 400 mg, 800 mg and 1200 mg. ESL efficacy and tolerability was evaluated in subjects with and without clinically relevant depressive symptoms at baseline, as defined by Montgomery-Asberg depression rating scale score (MADRS) ≥10 and <10, respectively. MADRS score <10 have been previously shown to define remission from major depression (Affective Dis 2002; 72:177-184.) Results: Safety population comprised 796 patients (MADRS≥10, n=325; MADRS<10, n=471) and intention-to treat population included 751 patients (MADRS≥10, n=303; MADRS<10, n=448). Compared with placebo seizure frequency over the 12-week maintenance period (primary endpoint) was significantly reduced with ESL 800 mg and 1200 mg both in patients with MADRS score ≥10 (p=0.03 and p=0.004, respectively) and with MADRS score <10 (p=0.0007 and p=0.0003, respectively) (table 1). Responder rate (≥50% reduction in seizure frequency) was: MADRS score ≥10 group = 13% with placebo, 32% with ESL 800 mg and 35% with ESL 1200 mg; MADRS score <10 group = 23% with placebo, 39% with ESL 800 mg and 49% with ESL 1200 mg. Median relative reduction in seizure frequency was: MADRS score ≥10 group = -4% with placebo, -31% with ESL 800 mg and -30% with ESL 1200 mg; MADRS score <10 group = -20% with placebo, -38% with ESL 800 mg and -48% with ESL 1200 mg. Incidence of treatment-emergent adverse events (TEAEs) was similar in MADRS score ≥10 group (55.8% with placebo, 63.4% with ESL 800 mg and 73.8% with ESL 1200 mg) and in MADRS score <10 group (45.6% with placebo, 69.2% with ESL 800 mg and 67.0% with ESL 1200 mg) (table 2). Conclusions: In this post-hoc exploratory analysis, once-daily ESL 800 mg and 1200 mg adjunctive therapy was significantly superior to placebo in reducing POS in adult patients with co-morbid clinically relevant depressive symptoms. This subgroup of patients with MADRS scores ≥10 at baseline was particularly drug resistant as compared to patients without clinically relevant depressive symptoms (MADRS scores<10) as shown by a worse seizure control either in placebo and ESL treated groups.