Metabolic syndrome in patients enrolled in a clinical trial of aripiprazole in the maintenance treatment of bipolar I disorder: a post hoc analysis of a randomized, double-blind, placebo-controlled trial

Abstract

Objective: To compare the effects of maintenance treatment with aripiprazole or placebo on the incidence of metabolic syndrome in bipolar disorder.

Method: Patients with DSM-IV bipolar I disorder were stabilized on aripiprazole therapy for 6-18 weeks prior to double-blind random assignment to aripiprazole or placebo for 26 weeks. The rate of metabolic syndrome in each group was calculated at maintenance phase baseline (randomization) and endpoint for evaluable patients using a last-observation-carried-forward (LOCF) approach. Metabolic syndrome was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. The study was conducted from March 2000 to June 2003 at 76 centers in Argentina, Mexico, and the United States.

Results: At entry into the maintenance phase, 45/125 patients (36.0%) overall met criteria for metabolic syndrome. Mean changes in the 5 components of metabolic syndrome (waist circumference, triglyceride levels, high-density lipoprotein cholesterol level, blood pressure, and glucose level) from baseline to week 26 were small except for a meaningful reduction in triglycerides (placebo -18.9 mg/dL; aripiprazole -11.5 mg/dL). By the end of the maintenance phase (endpoint, LOCF), 5/18 placebo-treated patients (27.8%) and 4/14 aripiprazole-treated patients (28.6%) no longer met metabolic syndrome criteria. The proportion of patients with metabolic syndrome was similar in the placebo and aripiprazole groups at both baseline and week 26. There were no significant changes in any of the individual components of metabolic syndrome between aripiprazole- and placebo-treated patients during maintenance phase treatment.

Conclusions: The prevalence of metabolic syndrome in patients with bipolar disorder is higher than that commonly reported in the general population. The effect of 26 weeks of treatment with aripiprazole on the incidence of metabolic syndrome and its components was similar to placebo.

Trial registration: clinicaltrials.gov Identifier: NCT00036348.

© Copyright 2010 Physicians Postgraduate Press, Inc.

Figures

Figure 1

Mean change from maintenance phase baseline to Week 26 in the components of the metabolic syndrome (last observation carried forward data set) LS = Least squares. NS = Not significant. Mean ± SD baseline values for aripiprazole vs. placebo were as follows: glucose 90.4 ± 19.7 vs. 95.4 ± 32.4 mg/dL; triglycerides 139.3 ± 74.2 vs. 164.1 ± 148.3 mg/dL; high-density lipoprotein cholesterol (HDL-C) 49.7 ± 14.4 vs. 52.7 ± 21.7 mg/dL; systolic blood pressure 118.5 ± 13.1 vs. 117.6 ± 13.4 mmHg; diastolic blood pressure 72.6 ± 9.8 vs. 73.6 ± 9.9 mmHg; waist circumference 99.3 ± 14.8 vs. 100.4 ± 22.0 cm

Figure 2

Incidence of metabolic syndrome status at maintenance phase endpoint (Week 26), stratified by the presence/absence of metabolic syndrome at maintenance phase baseline (randomization) (last observation carried forward)

Figure 3

The prevalence of each of the five components of metabolic syndrome in patients with bipolar I disorder at randomization and Week 26 (last observation carried forward data set) WC = waist circumference; TG = triglycerides; HDL-C, high-density lipoprotein cholesterol; BP, blood pressure; PG= plasma glucose.