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  • The International Journal of Neuropsychopharmacology, Volume 12, Issue 6
  • July 2009, pp. 773-782

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

  • Eileen Brown (a1), David L. Dunner (a2), Susan L. McElroy (a3), Paul E. Keck (a3) (a4), David H. Adams (a1), Elisabeth Degenhardt (a1), Mauricio Tohen (a1) (a5) and John P. Houston (a1)
  • DOI:
  • Published online: 11 December 2008

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.

Corresponding author
Address for correspondence: E. Brown, Ph.D., Eli Lilly and Company, Lilly Corporate Center, Drop Code 6046, Indianapolis, IN46285, USA. Tel.: (317) 655-1568Fax: (303) 258-9532Email:
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  • ISSN: 1461-1457
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