A Multicenter, Randomized, Double-Blind Study of the Effects of Aripiprazole in Overweight Subjects With Schizophrenia or Schizoaffective Disorder Switched From Olanzapine

Objective: Major mental disorders are associated with an increased risk for obesity-related cardiovascular mortality, leading to interest in risk-reduction approaches that target weight and risk-related plasma lipids, including use of antipsychotic agents with low metabolic risk. This multicenter, randomized, double-blind study compared the metabolic effects of aripiprazole versus olanzapine in overweight persons with schizophrenia or schizoaffective disorder who were previously on olanzapine treatment.

Method: In total, 173 subjects with DSM-IV-TR-defined schizophrenia or schizoaffective disorder were randomly assigned to receive aripiprazole (N = 88) or olanzapine (N = 85) for 16 weeks in a study conducted from March 30, 2004, to August 8, 2006. Primary and secondary endpoints were mean weight change from baseline and percentage change from baseline in fasting triglyceride levels, respectively.

Results: At week 16, weight decreased significantly with aripiprazole versus olanzapine (-1.8 vs. +1.41 kg; p = 7%) weight loss versus olanzapine (11.1% vs. 2.6%; p = .038), and a lower percentage of subjects receiving aripiprazole had clinically relevant weight gain (2.5% vs. 9.1%; p = .082). Mean percentage changes in fasting total cholesterol and high-density lipoprotein cholesterol at week 16 were significantly different with aripiprazole versus olanzapine, with no significant effects on glycemic laboratory measures. Mean Clinical Global Impressions-Improvement (CGI-I) scores for both groups were in the range of “no change” to “minimal improvement.” CGI-I endpoint scores were statistically significantly better with olanzapine (mean ± SE = 3.09 ± 0.16) versus aripiprazole (mean ± SE = 3.74 ± 0.15; p < .001), and more subjects discontinued aripiprazole (N = 32/88; 36%) than olanzapine (N = 22/85; 26%).

Conclusion: Significant improvements in weight and lipids observed during discontinuation of olanzapine and switch to aripiprazole treatment occurred with limited evidence of negative psychiatric effects, relative to uninterrupted continuation of olanzapine treatment. The results suggest that the potential value of therapeutic substitutions involving specific antipsychotic medications should be considered in overall efforts to reduce cardiovascular risk in this population.

Trial Registration: clinicaltrials.gov Identifier: NCT00095524′ ‹