A Comparison of Weight Change During Treatment With Olanzapine or Aripiprazole: Results From a Randomized, Double-Blind Study

Background: Weight gain is a side effect of therapy with many atypical antipsychotics and mayhave important clinical repercussions with respect to long-term health and treatment compliance. Theprimary objective of this double-blind study was to compare the safety and tolerability of aripiprazoleand olanzapine in patients with schizophrenia as evidenced by the percentage of patients exhibitingsignificant weight gain. Method: This was a 26-week, multicenter, randomized, double-blind, active-controlledtrial in patients with DSM-IV schizophrenia who were in acute relapse and required hospitalization.Significant weight gain was defined as a ≥ 7% increase in body weight from baseline. Bodyweight, Positive and Negative Syndrome Scale, and Clinical Global Impressions-Improvement scale(CGI-I) assessments were performed at baseline and at regular intervals during the study. The studyperiod was from April 2000 through June 2001. Results: 317 patients were randomly assigned to aripiprazole(N = 156) or olanzapine (N = 161). Compared with those treated with aripiprazole, a greaterproportion of patients treated with olanzapine exhibited clinically significant weight gain during thetrial. By week 26, 37% of olanzapine-treated patients had experienced significant weight gain comparedwith 14% of aripiprazole-treated patients (p < .001). Statistically significant differences inmean weight change were observed between treatments beginning at week 1 and sustained throughoutthe study. At week 26, there was a mean weight loss of 1.37 kg (3.04 lb) with aripiprazole comparedwith a mean increase of 4.23 kg (9.40 lb) with olanzapine among patients who remained on therapy(p < .001). Changes in fasting plasma levels of total cholesterol, high-density lipoprotein cholesterol,and triglycerides were significantly different in the 2 treatment groups, with worsening of the lipidprofile among patients treated with olanzapine. There was a consistent and sustained improvement insymptoms in patients who remained on therapy with either olanzapine or aripiprazole as assessed byCGI-I scores and responder rates throughout the study. Conclusion: Olanzapine had a greater impacton patients’ weight than aripiprazole. Significant differences in favor of aripiprazole were also observedin the effects of therapy on plasma lipid profile. Both treatment groups achieved comparableclinically meaningful improvements on efficacy measures. The observed effects on weight and lipidsindicate a potentially lower metabolic and cardiovascular risk in patients treated with aripiprazolecompared with those treated with olanzapine.