Long-Term Olanzapine Treatment: Weight Change and Weight-Related Health Factors in Schizophrenia

Background: Weight change and the weight-related health factors of nonfasting serum glucose, serum cholesterol, and diastolic blood pressure levels were analyzed in patients with DSM-III-R schizophrenia and related disorders who received treatment with olanzapine for up to 3 years, and comparisons were made to patients treated with haloperidol. Baseline body mass index (BBMI; kg/m2) and dose (mg/day) were investigated as predictors of long-term weight change experienced during olanzapine treatment.

Method: This analysis retrospectively examined 573 patients receiving olanzapine and 103 patients receiving haloperidol for 39 weeks or more from a study of 1996 patients randomly assigned 2:1 to either olanzapine, 5 to 20 mg/day, or haloperidol, 5 to 20 mg/day. After 6 weeks of acute therapy, patients continued for 1 year or more with either double-blind or open-label olanzapine therapy or double-blind haloperidol therapy.

Results: Mean weight gain for olanzapine-treated patients observed for a median of 2.54 years trended toward a plateau after the first 39 weeks of treatment with a last-observation-carried-forward mean weight change of 6.26 kg (13.8 lb) and a median of 5.90 kg (13.0 lb). This was significantly higher than that for haloperidol-treated patients, whose mean weight gain was 0.69 kg (1.5 lb) after 1.15 years (p < .001). Patients with higher BBMI (> 27.6) gained significantly less weight during treatment with olanzapine than their lighter counterparts (BBMI < 27.6) (p < .001). The effect of olanzapine dose on weight was not significant (p >= .183). Median serum glucose at endpoint was not significantly associated (p = .096) with weight change for olanzapine. Median serum cholesterol and diastolic blood pressure for olanzapine-treated patients at endpoint showed a relationship with weight change that was statistically (p <= .001) but not clinically significant. The difference in incidence of elevated serum glucose, cholesterol, or diastolic blood pressure between olanzapine and haloperidol therapy groups was not different (p > .05).

Conclusion: Mean weight gain during olanzapine treatment trended toward a plateau after the initial 39 weeks of treatment with no further significant gain out to 3 years. Higher BBMI was predictive of a lower long-term weight gain, while dose was not a significant predictor of greater longer term weight change. The relationship between weight change and glucose was not statistically significant. The association between weight change and changes in cholesterol as well as changes in diastolic blood pressure was statistically significant but not considered clinically relevant based on the ranges observed.

J Clin Psychiatry 2001;62(2):92-100