Relationship between Adjunctive Eslicarbazepine Acetate (ESL) Use and Incidence of Psychiatric Adverse Events in Patients Taking Psychotropic Drugs in Three Phase III ESL Trials (P3.243)

Objective: To evaluate the potential relationship between ESL use and incidence of ‘psychiatric’ adverse events (AEs) in patients taking concomitant medications with putative beneficial or detrimental psychotropic effects. Background: ESL (and other members of the dibenzazepine carboxamide class of antiepileptic drugs [AEDs]) are structurally related to tricyclic antidepressants; the potential for AEDs of this class to have psychotropic effects is therefore of interest. Design/Methods: An exploratory post-hoc analysis of data pooled from three Phase III studies of adjunctive ESL (BIA-2093-301, −302 and −304) in patients with treatment-refractory partial-onset seizures was conducted. Patients received placebo, ESL 400 mg (studies 301 and 302 only), 800 mg, or 1200 mg once daily. Reports of AEs classed as ‘psychiatric’ were evaluated according to concomitant use of antidepressants, and baseline use of AEDs with putative beneficial (carbamazepine [CBZ], lamotrigine [LTG] or valproic acid [VPA]) or detrimental (levetiracetam [LEV]) psychotropic effects. Results: There were 1447 patients in the safety population (placebo, n = 426; ESL, n = 1021). Proportions of patients with ‘any psychiatric AE’ in the placebo and ESL groups were comparable between the + and − CBZ/LTG/VPA groups, and between the + and − LEV groups; similarly for ‘depression’ and ‘anxiety’. Incidence of psychiatric AEs was comparable between the placebo and ESL groups for + and − antidepressants, with a greater overall incidence among patients using antidepressants (+ antidepressants: placebo 25.0%, ESL 23.6%; -antidepressants: placebo 9.1%, ESL 9.2%). There were no notable differences in the incidences of mild, moderate or severe psychiatric AEs between patients taking ESL or placebo, whether or not they were taking different psychotropic drugs at baseline. Conclusions: The incidence of psychiatric AEs in patients using agents with putative beneficial or detrimental psychotropic effects was not notably influenced by concomitant use of adjunctive ESL. Study Supported by: Sunovion Pharmaceuticals Inc. Disclosure: Dr. Harden has received royalty payments from Wiley and Up-to-date. Dr. Carreno has received personal compensation for activities with UCB Pharma, Eisai, and BIAL as a member of an advisory board and from Eisai, BIAL, and Esteve as a speaker. Employee of BIAL - Portela & Ca, S.A.. Dr. Soares-da-Silva has received personal compensation for activities with Bial- Portela & Ca S.A as an employee. Dr. Jung has received personal compensation for activities with Sunovion Pharmaceuticals Inc. as an employee. Dr. Grinnell has received personal compensation for activities with Sunovion Pharmaceuticals as an employee. Dr. Blum has received personal compensation for activities with Sunovion Pharmaceuticals Inc. as an employee.