The International Journal of Neuropsychopharmacology

Research Article

A double-blind, randomized, placebo-controlled prophylaxis trial of oxcarbazepine as adjunctive treatment to lithium in the long-term treatment of bipolar I and II disorder

Eduard Vietaa1 c1, Nuria Cruza1, Javier García-Campayoa2, Rosario de Arcea3, Jose Manuel Crespoa4, Vicens Vallèsa5, Josefina Pérez-Blancoa6, Ernesto Rocaa7, Jose Manuel Olivaresa8, Angel Moríñigoa9, Raul Fernández-Villamora10 and Merce Comesa1

a1 Bipolar Disorders Program, Hospital Clinic, University of Barcelona, IDIBAPS, CIBER-SAM, Barcelona, Spain

a2 Department of Psychiatry, Miguel Servet University Hospital, Zaragoza, Spain

a3 Clinica Puerta del Hierro, Madrid, Spain

a4 Department of Psychiatry, University Hospital of Bellvitge, CIBER-SAM, Barcelona, Spain

a5 Department of Psychiatry, Hospital de Terrassa, Consorci Sanitari de Terrassa, Barcelona, Spain

a6 Department of Psychiatry, Hospital de Sant Pau, CIBER-SAM, Barcelona, Spain

a7 Hospital de Valencia, Valencia, Spain

a8 Hospital Nicolás Peña, Vigo, Spain

a9 Hospital Universitario Virgen de Valme, Sevilla, Spain

a10 C.S.M. Macarena Centro, Sevilla, Spain


We evaluated the prophylactic efficacy and the long-term tolerability of oxcarbazepine administration in the treatment of bipolar I and II disorder as an adjunctive therapy to lithium. We conducted a 52-wk, double-blind, randomized, placebo-controlled, parallel-group, multicentre, clinical trial. Bipolar I and II DSM-IV outpatients, having had two or more episodes in the last year, but currently being in remission, were randomly assigned on a 1:1 ratio to oxcarbazepine (n=26) or placebo (n=29) as adjuncts to ongoing treatment with lithium. The primary efficacy variable was the length of the remission period assessed by means of the Young Mania Rating Scale (YMRS) and Montgomery–Asberg Depression Rating Scale (MADRS). Other assessments were the Clinical Global Impression (CGI-BP-M), functional activity (GAF), anxiety (HAMA) and impulsiveness (BIS-11). The average time until first recurrence of any type was 19.2±13.9 wk and 18.6±17.0 wk for oxcarbazepine and placebo respectively (p=0.315). Ten (38.46%) patients had a recurrence of any kind in the oxcarbazepine group vs. 17 (58.62%) in the placebo group (p=0.1354). There was a trend for depressive episodes being less likely in the oxcarbazepine group compared to the placebo group (11.54% and 31.03% respectively, p=0.085), and for better functionality with the GAF (p=0.074). Impulsivity was significantly better prevented by oxcarbazepine (p=0.0443). Overall, oxcarbazepine was well tolerated. This pilot, randomized clinical trial, suggests that oxcarbazepine might have some prophylactic efficacy with regards to impulsivity and perhaps mood episodes in patients taking lithium, although further, adequately powered controlled trials are needed to confirm these findings.

(Received July 25 2007)

(Reviewed September 16 2007)

(Revised November 20 2007)

(Accepted January 20 2008)

(Online publication March 17 2008)


c1 Address for correspondence: Dr E. Vieta, Bipolar Disorders Program, Clinical Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBER-SAM, Villarroel 170/Rossello 140, Barcelona 08036, Spain. Tel.: 34 932 275 401 Fax: 34 932 279 876 E-mail: