title: Assessment of the efficacy and safety of eslicarbazepine acetate in acute mania and prevention of recurrence: experience from multicentre, double-blind, randomised phase II clinical studies in patients with bipolar disorder I.
abstract: BACKGROUND
  Eslicarbazepine acetate (ESL) is an anticonvulsant approved as an adjunctive therapy in adults with partial-onset seizures.
  
  
  OBJECTIVE
  To evaluate the efficacy, safety and tolerability of ESL in the treatment of acute mania and prevention of recurrence in bipolar disorder I.
  
  
  METHODS
  Two 3-week multicentre, double-blind, randomised, placebo-controlled studies in acute mania (study BIA-2093-203: dose titrated by response, ESL 600-1800mg or 800-2400mg, once-daily; study BIA-2093-204: fixed doses of 600, 1200 and 1800mg, once-daily) were followed by a recurrence prevention study consisting of a 2-week open-label period (900mg, once-daily) continued by a double-blind, parallel-group, fixed dose (300, 900 and 1800mg, once-daily) period for a minimum of 6 months. The primary endpoint was changed from baseline until the end of the 3-week treatment period in Young Mania Rating Scale (YMRS) in studies BIA-2093-203 and BIA-2093-204, and the proportion of patients showing no worsening according to the Clinical Global Impressions - Bipolar Version (CGI-BP) over Part II in study BIA-2093-205.
  
  
  RESULTS
  In study BIA-2093-203 (n=160, ITT), neither dose group was statistically different from placebo in the primary endpoint, though the ESL 800-2400mg showed a greater reduction in YMRS score (p=0.0523). CGI-BP score changes for mania and overall bipolar illness indicate a significant improvement in patient symptomatology for the ESL 800-2400mg group (from preceding and worst phase) and for ESL 600-1800mg group (from worst phase only) when compared to placebo. Study BIA-2093-204 (n=38) results were inconclusive due to premature termination caused by recruitment difficulties. In study BIA-2093-205 (n=85, ITT), at least 50% of patients showed no worsening in all treatment groups (p=0.250). ESL adverse events were mostly of mild and moderate intensities and consistent with previously reported observations for ESL.
  
  
  CONCLUSIONS
  ESL treatment was not significantly different from placebo in manic patients in the primary outcome, but secondary outcomes may be suggestive of efficacy. The recurrence prevention study provides preliminary support for efficacy of ESL in patients recovered from an acute manic episode.
authors.affiliation: Institute of Neuroscience, Newcastle University, Wolfson Research Centre, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, United Kingdom.
authors.forename: Heinz
authors.initials: H
authors.lastname: Grunze
authors.affiliation: RAM Salud Mental, Buenos Aires, Argentina.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Kotlik
authors.affiliation: Department of Research and Development, BIAL - Portela & C(a), S.A., S. Mamede do Coronado, Portugal.
authors.forename: Raquel
authors.initials: R
authors.lastname: Costa
authors.affiliation: Department of Research and Development, BIAL - Portela & C(a), S.A., S. Mamede do Coronado, Portugal.
authors.forename: Teresa
authors.initials: T
authors.lastname: Nunes
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Coimbra, Portugal.
authors.forename: Amílcar
authors.initials: A
authors.lastname: Falcão
authors.affiliation: Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Porto, Portugal; Health Sciences Department, University of Aveiro, Portugal.
authors.forename: Luis
authors.initials: L
authors.lastname: Almeida
authors.affiliation: Department of Research and Development, BIAL - Portela & C(a), S.A., S. Mamede do Coronado, Portugal; Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Porto, Portugal; MedInUP - Center for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal. Electronic address: psoares.silva@bial.com.
authors.forename: Patrício
authors.initials: P
authors.lastname: Soares-da-Silva
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000517:prevention & control*; D003984:Dibenzazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D055502:Secondary Prevention / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D014150:Antipsychotic Agents; D003984:Dibenzazepines; C416835:eslicarbazepine acetate
keywords: Bipolar disorder; Efficacy; Eslicarbazepine acetate; Mania; Recurrence prevention; Safety