Research Article

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

Eileen Brown^a1 c1, David L. Dunner^a2, Susan L. McElroy^a3, Paul E. Keck Jr.^a3a4, David H. Adams^a1, Elisabeth Degenhardt^a1, Mauricio Tohen^a1a5 and John P. Houston^a1

^a1 Lilly Research Laboratories, Indianapolis, IN, USA

^a2 Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA

^a3 Psychopharmacology Research Program, Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH, USA

^a4 Mental Health Service Line and General Clinical Research Center, Cincinnati Veterans Affairs Medical Center, Cincinnati, OH, USA

^a5 McLean Hospital, Harvard Medical School, Belmont, MA, USA

Abstract

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.

(Received June 30 2008)

(Reviewed July 28 2008)

(Revised October 31 2008)

(Accepted November 11 2008)

(Online publication December 11 2008)

Key Words:

• Antipsychotic;
• bipolar depression;
• clinical trial;
• mania;
• response

Correspondence:

^c1 Address for correspondence: E. Brown, Ph.D., Eli Lilly and Company, Lilly Corporate Center, Drop Code 6046, Indianapolis, IN 46285, USA. Tel.: (317) 655-1568 Fax: (303) 258-9532 Email: ebrown@lilly.com