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A 7-Week, Randomized, Double-Blind Trial of Olanzapine/Fluoxetine Combination Versus Lamotrigine in the Treatment of Bipolar I DepressionEileen B. Brown, Ph.D.; Susan L. McElroy, M.D.; Paul E. Keck, Jr., M.D.; Ahmed Deldar, Ph.D.; David H. Adams, Ph.D.; Mauricio Tohen, M.D., Dr.P.H.; and Douglas J. Williamson, M.D., M.R.C.Psych.Objective: Determine the efficacy and tolerability of olanzapine/fluoxetine combination (OFC) for treatment of acute bipolar I depression compared with lamotrigine. Method: The 7-week, acute phase of a randomized, double-blind study compared OFC (6/25, 6/50, 12/25, or 12/50 mg/day; N = 205) with lamotrigine ([LMG] titrated to 200 mg/day; N = 205) in patients with DSMIV-diagnosed bipolar I disorder, depressed. The study was conducted from November 2003 to August 2004. Results: Completion rates were similar between treatments (OFC, 66.8% vs. LMG, 65.4%; p = .835). OFC-treated patients had significantly greater improvement than lamotrigine-treated patients in change from baseline across the 7-week treatment period on the Clinical Global Impressions-Severity of Illness scale (primary outcome) (p = .002, effect size = 0.26), Montgomery-Asberg Depression Rating Scale (MADRS) (p = .002, effect size = 0.24), and Young Mania Rating Scale total scores (p = .001, effect size = 0.24). Response rates did not significantly differ between groups when defined as > = 50% reduction in MADRS score (OFC, 68.8% vs. LMG, 59.7%; p = .073). Time to response was significantly shorter for OFC-treated patients (median days [95% CI] = OFC, 17 [14 to 22] vs. LMG, 23 [21 to 34]; p = .010). There was a significant difference in incidence of "suicidal and self-injurious behavior" adverse events (OFC, 0.5% vs. LMG, 3.4%; p = .037). Somnolence, increased appetite, dry mouth, sedation, weight gain, and tremor occurred more frequently (p < .05) in OFC-treated patients than lamotrigine-treated patients. Weight, total cholesterol, and triglyceride levels were significantly elevated in OFC-treated patients compared with lamotrigine-treated patients (all p < = .001). Conclusions: Patients with acute bipolar I depression had statistically significantly greater improvement in depressive and manic symptoms, more treatment-emergent adverse events, greater weight gain, and some elevated metabolic factors with OFC than lamotrigine. Treatment differences were of modest size. (J Clin Psychiatry 2006;67:1025-1033) Received April 14, 2005; accepted Feb. 2, 2006. From Lilly Research Laboratories, Indianapolis, Ind. (Drs. Brown, Deldar, Adams, Tohen, and Williamson); Psychopharmacology Research Program, Department of Psychiatry, University of Cincinnati College of Medicine, and Mental Health Service Line and General Clinical Research Center, Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio (Drs. McElroy and Keck); and McLean Hospital, Harvard Medical School, Belmont, Mass. (Dr. Tohen). This study was funded by Eli Lilly and Co., Indianapolis, Ind. Financial disclosure appears at the end of the article. Acknowledgment is given to Jan Short and Stacia L. Mellinger for their editorial and technical assistance in the preparation of this manuscript. Mss. Short and Mellinger are employees of Eli Lilly. Corresponding author and reprints: Eileen B. Brown, Ph.D., Eli Lilly and Co., Lilly Corporate Center, Drop Code 4133, Indianapolis, IN 46285 (e-mail: ebrown@lilly.com). |