Aripiprazole added to overweight and obese olanzapine-treated schizophrenia patients.
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.
Henderson
David C
DC
Schizophrenia Program, Massachusetts General Hospital, Boston, MA, USA. dchenderson@partners.org
Fan
Xiaoduo
X
Copeland
Paul M
PM
Sharma
Bikash
B
Borba
Christina P
CP
Boxill
Ryan
R
Freudenreich
Oliver
O
Cather
Corinne
C
Evins
A Eden
AE
Goff
Donald C
DC
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000068180:Aripiprazole; D001569:Benzodiazepines / Q000009:adverse effects* / Q000627:therapeutic use; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000139:chemically induced; D000077152:Olanzapine; D050177:Overweight / Q000139:chemically induced; D010879:Piperazines / Q000009:adverse effects* / Q000627:therapeutic use; D015363:Quinolones / Q000009:adverse effects* / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D014280:Triglycerides / Q000097:blood
D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D014280:Triglycerides; D001569:Benzodiazepines; D000068180:Aripiprazole; D002097:C-Reactive Protein; D002784:Cholesterol; D005947:Glucose; D000077152:Olanzapine