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Aripiprazole Added to Overweight and Obese Olanzapine-Treated Schizophrenia Patients

Henderson, David C. MD*†; Fan, Xiaoduo MD, MS*†; Copeland, Paul M. MD; Sharma, Bikash MBBS*; Borba, Christina P. MPH*; Boxill, Ryan PhD*†; Freudenreich, Oliver MD*†; Cather, Corinne PhD*†; Evins, A. Eden MD*†; Goff, Donald C. MD*†

Journal of Clinical Psychopharmacology: April 2009 - Volume 29 - Issue 2 - p 165-169
doi: 10.1097/JCP.0b013e31819a8dbe
Brief Reports

Olanzapine treatment has been associated with clinically meaningful weight increases, hypertriglyceridemia, insulin resistance, and diabetes mellitus. There are few options for olanzapine responders who fail other antipsychotic agents. Aripiprazole is a potent (high-affinity) partial agonist at D2 and 5-HT1A receptors and a potent antagonist at 5-HT2A receptor and is associated with less weight gain than olanzapine. We report the results of a 10-week placebo-controlled, double-blind crossover study that examined 15 mg/d aripiprazole's effects on weight, lipids, glucose metabolism, and psychopathology in overweight and obese schizophrenia and schizoaffective disorder subjects treated with a stable dose of olanzapine. During the 4 weeks of aripiprazole treatment, there were significant decreases in weight (P = 0.003) and body mass index (P = 0.004) compared with placebo. Total serum cholesterol (P = 0.208), high-density lipoprotein cholesterol (HDL-C; P = 0.99), HDL-2 (P = 0.08), HDL-3 (P = 0.495), and low-density lipoprotein cholesterol (P = 0.665) did not change significantly comparing aripiprazole treatment to placebo treatment. However, total serum triglycerides (P = 0.001), total very low-density lipoprotein cholesterol (VLDL-C; P = 0.01), and VLDL-1C and VLDL-2C (P = 0.012) decreased significantly during the aripiprazole treatment phase. The VLDL-3C tended lower during aripiprazole, but the decrease was not significant (P = 0.062). There was a decrease in C-reactive protein comparing aripiprazole treatment to placebo, although it did not reach significance (P = 0.087). The addition of aripiprazole to a stable dose of olanzapine was well tolerated and resulted in significant improvements on several outcome measures that predict risk for medical morbidity.

From the *Schizophrenia Program, Massachusetts General Hospital; and †Harvard Medical School, Boston, MA.

Received August 25, 2008; accepted after revision December 30, 2008.

Reprints: David C. Henderson, MD, Freedom Trail Clinic, 25 Staniford St, Boston, MA 02114 (e-mail:

This project was supported by an unrestricted investigator-initiated research grant from Eli Lilly and Co. These data have not been published or presented elsewhere.

© 2009 Lippincott Williams & Wilkins, Inc.