Olanzapine plus carbamazepine v. carbamazepine alone in treating manic episodes

Background: Combinations of olanzapine and carbamazepine are often used in clinical practice in the management of mania. Aims: To assess the efficacy and safety of olanzapine plus carbamazepine in mixed and manic bipolar episodes. Method: Randomised, double-blind, 6-week trial of olanzapine (10-30 mg/day) plus carbamazepine (400-1200 mg/day; n=58) v. placebo plus carbamazepine (n=60) followed by open-label, 20-week olanzapine (10-30 mg/day) plus carbamazepine (400-1200 mg/day, n=86), with change in manic symptoms as main outcome measure. Safety and pharmacokinetics were also evaluated. Results: There were no significant differences (baseline to endpoint) in efficacy measures between treatment groups, but at 6 weeks triglyceride levels were significantly higher (P=0.008) and potentially clinically significant weight gain (≥7%) occurred more frequently (24.6% v. 3.4%, P=0.002) in the combined olanzapine and carbamazepine group. Carbamazepine reduced olanzapine concentrations but olanzapine had no effect on carbamazepine concentrations. Conclusions: The combination of olanzapine and carbamazepine did not have superior efficacy to carbamazepine alone. The increases in weight and triglycerides observed during combination treatment are a matter of concern. Declaration of interest: Study sponsor: Eli Lilly & Company (employees: M.T., R.B., T.Q., O.O., W.W., F.M. and L.K.). Full declaration in Acknowledgements.