Combinations of olanzapine and carbamazepine are often used in clinical practice in the management of mania.

To assess the efficacy and safety of olanzapine plus carbamazepine in mixed and manic bipolar episodes.

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.

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.

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.