Weight Gain During Treatment of Bipolar I Patients With Olanzapine

John Hennen, Ph.D.; Roy H. Perlis, M.D.; Gary Sachs, M.D.; Mauricio Tohen, M.D., Dr. P.H.; and Ross J. Baldessarini, M.D.

Background: Body weight increase during long-term treatment with olanzapine in schizophrenia patients is well documented, but weight gain and its association with other medical measures are less well evaluated in bipolar disorder patients.

Method: We analyzed data from a 3-week, randomized, placebo-controlled trial of olanzapine for acute mania in DSM-IV bipolar I patients, followed by open continuation treatment with olanzapine up to a year. We examined factors associated with increased body mass index (BMI), including ratings of clinical change and selected physiologic measures.

Results: Among 113 subjects treated with olanzapine for a mean ± SD of 28.6 ± 19.9 weeks, BMI increased from a baseline mean of 28.8 ± 6.2 kg/m², by 7.9 ± 10.8% (p < .001), into the obese range (31.0 ± 6.1 kg/m²). Initial BMI change (first 3 weeks of drug exposure) predicted final BMI increases (Spearman rank correlation r_s = 0.32, p < .001). History of longer illness (p = .006) and lifetime substance abuse (p = .02) were associated with below-median BMI increases. BMI increased much more among 40 subjects achieving symptomatic recovery than in the 73 who did not (by 11.9 ± 13.2% vs. 5.3 ± 7.7%; p = .004), with correspondingly longer olanzapine exposure (44.7 ± 11.8 vs. 19.7 ± 17.7 weeks; p < .001) at similar doses. On average, serum cholesterol increased 4.8 times more (17.5% vs. 3.6%) and endpoint cholesterol levels were newly 240 mg/dL or greater 3.6 (95% CI = 1.5 to 8.0) times more frequently in subjects with above-median BMI gain, who also experienced significantly larger increases in systolic and diastolic blood pressure, pulse rates, and nonfasting serum glucose than low-BMI-gain subjects.

Conclusions: Weight gain associated with long-term olanzapine treatment for mania was common, substantial, time-dependent, predicted by initial increases, and temporally associated with significant changes in cardiovascular and metabolic measures in bipolar I patients with prolonged illness and already-high basal BMI. An association of weight gain with favorable clinical response probably reflects longer olanzapine treatment.

(J Clin Psychiatry 2004;65:1679-1687)

Received July 27, 2004; accepted Oct. 5, 2004. From the Department of Psychiatry, Harvard Medical School, Boston, Mass. (Drs. Hennen, Perlis, Sachs, and Baldessarini); the Bipolar and Psychotic Disorders Program, McLean Hospital, Belmont, Mass. (Drs. Hennen and Baldessarini); the Bipolar Disorder Unit, Department of Psychiatry, Massachusetts General Hospital, Boston (Drs. Perlis and Sachs); and Lilly Research Laboratories, Indianapolis, Ind. (Dr. Tohen).

Supported, in part, by an award from the Eli Lilly Corporation (Dr. Hennen) and grants from the Bruce J. Anderson Foundation and the McLean Private Donors Neuropsychopharmacology Research Fund (Dr. Baldessarini). Eli Lilly and Company supported the original trial on which this study was based.

Financial disclosure is listed at the end of the article.

Among colleagues at Lilly Research Laboratories, Angela Evans, Ph.D., provided valuable organizational assistance with the study, and Rick Risser, M.S., assisted with compiling and pooling data files.

Corresponding author and reprints: John Hennen, Ph.D., Biostatistics Laboratory, Administration Building, McLean Hospital, 115 Mill St., Belmont, MA 02478-9106 (e-mail: jhennen@mclean.org).