A new study showed that a significantly greater number of patients with schizophrenia who were treated with olanzapine experienced clinically significant weight gain compared to aripiprazole. Patients completing the study who were treated with aripiprazole showed a mean weight decrease of 1.37 kg (-3.01 lbs), while patients treated with olanzapine gained an average of 4.23 kg (+9.3 lbs). Differences favoring aripiprazole were observed in the incidence rates for elevated total cholesterol, LDL ("bad" cholesterol) and triglyceride levels. The study also demonstrated comparable efficacy for aripiprazole and olanzapine in acute relapse of schizophrenia across the course of the 26-week trial. These data were presented at the 156th Annual Meeting of the American Psychiatric Association.
"Recent research suggests that people with schizophrenia may be at higher risk for diabetes and hyperlipidemia than the general population. Therefore, it is important to understand the impact medications can have on weight and other risk factors that may contribute to the onset of diabetes or other metabolic disorders," said Dr. Peter Weiden, director of the Schizophrenia Research Program and Professor of Psychiatry, State University of New York Health Science. "Physicians need to consider overall health when treating patients with a chronic illness such as schizophrenia, who are predisposed to diabetes."
In this 26-week, double-blind, multi-center study, 317 patients with acute relapse of schizophrenia were randomized to receive either aripiprazole (15-30 mg/day; mean=25.1 mg/day) or olanzapine (10-20 mg/day; mean=16.5 mg/day).
The major findings of this head-to-head study include:
Significantly more olanzapine-treated patients experienced clinically significant weight gain (defined as >7 per cent increase from baseline weight) than aripiprazole-treated patients (37 per cent vs. 14 per cent; p<0.001).
Significantly more patients exhibited weight gain with olanzapine than with aripiprazole regardless of whether they entered the study defined by Body Mass Index (BMI) as underweight (BMI<23), average weight (BMI 23-27) or overweight (BMI>27).
Among patients completing the study, those treated with aripiprazole showed a mean weight loss of 1.37 kg (-3.01 lbs), while patients treated with olanzapine showed a mean weight gain of 4.23 kg (+9.31 lbs; p<0.001). Significant differences in mean weight change between the two groups were observed from Week 1 onward.
Efficacy was comparable between aripiprazole and olanzapine as measured by observed improvement in Positive and Negative Symptom Severity (PANSS)-Total Score and Clinical Global Impression-Improvement (CGI-I) across the duration of the 26-week study.
A significantly greater percentage of olanzapine-treated patients who started with normal baseline values experienced elevated total cholesterol, LDL cholesterol and triglycerides during the course of the study compared to those treated with aripiprazole.
The majority of adverse events reported in this study occurred at a similar incidence rate in both the aripiprazole and olanzapine treatment groups. The most common (> 10 per cent) adverse events reported by aripiprazole-treated patients were insomnia, headache, anxiety, agitation, psychosis and dyspepsia, while the most common adverse events reported by olanzapine-treated patients were headache, insomnia, anxiety, somnolence, agitation, psychosis, lightheadedness and dyspepsia.
The only events showing a >5 per cent difference between aripiprazole and olanzapine groups were somnolence (8 per cent vs. 23 per cent, respectively) and headache (23 per cent vs. 32 per cent, respectively), both of which were more frequent in the olanzapine group. Incidence of prolactin elevation was significantly higher among the olanzapine group compared to the aripiprazole group (p<0.05). The overall incidence of extrapyramidal symptoms (EPS) was comparable for the aripiprazole and olanzapine groups. No patients in either group experienced clinically significant increases in QTc interval.
Aripiprazole, the most recently approved treatment for schizophrenia in the United States, Mexico, Brazil, Puerto Rico and Australia, has been prescribed for more than 100,000 people in the United States. Aripiprazole is available in 10 mg, 15 mg, 20 mg, and 30 mg tablets. When starting treatment, some patients experience side effects such as headache, anxiety, insomnia, nausea, vomiting, sleepiness, lightheadedness, restlessness, and constipation.
In short-term (4- and 6-week) placebo-controlled trials, there was no statistical difference in the incidence of discontinuation due to adverse events between patients treated with aripiprazole and placebo (7 per cent and 9 per cent, respectively) or incidence of extrapyramidal syndrome (6 per cent vs. 6 per cent). In addition, studies showed that aripiprazole was associated with a moderate difference in sedation compared to placebo (11 per cent vs. 8 per cent, respectively), and did not cause significant QTc interval changes.