One of the partial solved issues in the treatment of Bipolar Disorders is mixed episode. Often, antidepressant monotherapy increases the risk of switching into mania/hypomania. Also, discontinuation of mood stabilizers leads to relapses. In long term treatment, adding mood stabilizers may help to avoid the disease burdens.

to estimate the clinical efficacy and acceptability, in mixed episodes, of valproate-VPA vs. carbamazepine-CBZ, associated or not with olanzapine (OLZ).

clinical open study including 51 patients (28-56 years), both sexes, with Bipolar Disorder-Mixed Episode (DSM-IV), mean scores YMRS=21,3 and MADRS=17,5 at baseline. Instruments: depression (MADRS), mania (YMRS), CGI-S, CGI-I, side effects, somatic conditions and relapse (follow-up: 6 month). We divided those patients in 3 groups: Group A: OLZ (17,5mg/day), N=17, Group B: OLZ+ CBZ (1250mg/day) N=17 and Group C OLZ+VPA (1350mg/day), N=17. After 4 weeks: 42 patients were responders (MADRS and YMRS< 50% vs. baseline), 9 drop-outs. Responders Group A: 11pts, Group B: 7pts, Group C: 16pts. The 6 month follow-up period we evaluated the relapses in all groups.

After 4 weeks, VPA and CBZ associated with OLZ were similarly effective, with an advantage in the OLZ+VPA group. The follow-up period demonstrate fewer relapses in the OLZ alone Group and OLZ+VPA Group versus OLZ+CBZ Group.

1.For the treatment of mixed episodes in Bipolar Disorder, OLZ monotherapy and OLZ+VPA seemed to be more effective and best tolerated. 2. In long term treatment, considering the different adverse events of VPA and CBZ, VPA may be more effective than CBZ.