Weight Gain During Treatment of Bipolar I Patients With Olanzapine

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.