Metabolic effects of olanzapine in patients with newly diagnosed psychosis

Abstract

Antipsychotic medications are associated with an increased risk of diabetes. Previous studies have also found an increased risk of type 2 diabetes mellitus in the relatives of schizophrenia probands. The aim of this study was to explore the metabolic adverse effects of olanzapine in a cohort of patients with newly diagnosed psychosis and minimal or no exposure to antipsychotics. Patients with newly diagnosed psychosis (n = 30) were enrolled in a 16-week open trial of olanzapine. Body mass index, fasting glucose, hemoglobin A1c, fasting insulin, IL-6, and a fasting lipid profile were measured at baseline and at 4-week intervals. There was a significant, linear increase over time in fasting glucose (P = 0.043), weight (P < 0.001), body mass index (P < 0.001), total cholesterol (P = 0.005), triglycerides (P = 0.003), and low-density lipoprotein (P = 0.013), but not hemoglobin A1c (P = 0.691), fasting insulin (P = 0.690), IL-6 (P = 0.877), or high-density lipoprotein (P = 0.446). An abnormal baseline IL-6 was a significant predictor of a greater increase in both total cholesterol (P < 0.01) and low-density lipoprotein (P < 0.01). Otherwise, neither parental history of type 2 diabetes mellitus nor baseline IL-6 predicted changes in metabolic measures. Changes in metabolic measures with olanzapine treatment can be detected early in the treatment of patients who are previously antipsychotic naive. The absence of a change in fasting insulin suggests a failure of pancreatic islet cells to compensate for the increase in fasting glucose.

Trial registration: ClinicalTrials.gov NCT00446992.

Conflict of interest statement

AUTHOR DISCLOSURE INFORMATION

Drs Fernandez-Egea and Garcia-Rizo have no conflicts of interest to disclose.

Figures

FIGURE 1

Flow of patients through the study.

FIGURE 2

Changes in metabolic measures over time in all subjects (n = 30). A, Weight and BMI. In the univariate linear regression models, there was a significant, linear increase over time in weight (P < 0.001) and BMI (P < 0.001). B, Fasting glucose and fasting insulin. In the univariate linear regression models, there was a significant, linear increase over time in fasting glucose (P = 0.043), but not in fasting insulin (P = 0.690). C, Total cholesterol and LDL. In the univariate linear regression models, there was a significant, linear increase over time in total cholesterol (P = 0.005) and LDL (P = 0.013). Baseline abnormal IL-6 (≥5) was a significant predictor of a greater increase in both total cholesterol (P < 0.01) and LDL (P < 0.01) in a repeated-measures analysis of variance.