Olanzapine/fluoxetine combination vs. lamotrigine in the 6-month treatment of bipolar I depression

To determine the efficacy and tolerability of olanzapine/fluoxetine combination (OFC) compared with lamotrigine (Lam) for long-term treatment of bipolar I depression, this 25-wk, randomized, double-blind Study compared OFC (6/25, 6/50, 12/25, or 12/50 mg/d, n = 205) with Lam titrated to 200 mg/d (n = 205) in patients with bipolar I disorder, depressed. A protocol-specified analysis of 7-wk outcomes was previously reported. Outcome measures included Clinical Global Impressions - Severity of Illness (CGI-S) (primary), Montgomery-Asberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS) scores. OFC-treated patients had significantly greater improvement than Lam-treated patients over 25 wk on CGI-S (p = 0.008), MADRS (p = 0.005), and YMRS (p < 0.001) scores, and from baseline across visits from week 5 (titration complete) to the end of the Study on CGI-S (p = 0.043), MADRS (p = 0.017), and YMRS (p = 0.001) scores. Of patients in remission after the 7-wk acute phase, there was no significant difference between treatment groups in the incidence of relapse (MADRS > 15, p = 0.528). Rate of treatment-emergent mania was not significantly different by treatment (p = 0.401). OFC-treated patients had more frequent (p < 0.05) somnolence, increased appetite, dry mouth, sedation, weight gain, and tremor; Lam-treated patients had more frequent insomnia. There was a significant difference in incidence of treatment-emergent cholesterol >= 240 (p < 0.001) and in weight gain of >= 7% (p < 0.001) in favour of the Lam group. Patients with bipolar I depression had significantly greater symptom improvement over 25 wk on OFC compared with Lam. There was no treatment difference in incidence of relapse. OFC-treated patients had more treatment-emergent adverse events and greater incidence of weight gain and hypercholesterolaemia.