Abstracts

Rationale: An increase in the risk of suicide has been associated with the use of antiepileptic drug therapy. To gain a thorough understanding of the risk of depression in association with the use of eslicarbazepine acetate (ESL), the depressive symptomatology during long-term add-on treatment was analyzed in the pooled population of a 1-year open-label extension to three Phase III studies. Methods: During the open-label extension of three phase III studies with ESL, in which most subjects were treated with ESL 800 mg once-daily (range: 400-1600 mg), the Montgomery Asberg Depression Rating Scale (MADRS) was applied at baseline and following 1-year of treatment or early discontinuation. Subjects (n=828) were stratified by their baseline MADRS Total Score into four categories: Severe Symptoms (score ≥31; n=13); Moderate Symptoms (score <31 and ≥25; n=30); Mild Symptoms (score <25 and >10; n=246); and No Symptoms (score ≤10; n=539). For each MADRS score category, the results at the end of the treatment period (i.e., 1 year or early discontinuation) were compared with those at baseline. Results: The change from baseline in total MADRS score by severity category at baseline in the intention-to-treat (ITT) population is presented in Table I. The highest mean decrease was reported in subjects of the MADRS Severe Symptoms category at baseline (-18.8; p<0.0001). The mean decrease was -10.1 (p<0.0001) for subjects in the MADRS Moderate Symptoms category and -5.4 (p<0.0001) for subjects in MADRS Mild Symptoms category at baseline. Overall there was no change in the MADRS score for subjects in MADRS No Symptoms category at baseline. The analysis in the per-protocol (PP) population showed similar results. Subjects either improved or stayed in the same category with very few exceptions. There were no reported cases of suicide or suicide attempt. Conclusions: In this pooled population of a 1-year open-label extension to three Phase III studies, 289 of 828 (34.9%) of subjects with refractory epilepsy had mild to severe symptoms of depression at baseline. Subjects with severe, moderate or mild depressive symptoms reported significant improvements from baseline during long-term open-label adjunctive therapy with ESL, as measured by MADRS. None of the subjects attempted suicide during the study. Supported by BIAL- Portela & Co, SA