title: Aripiprazole added to overweight and obese olanzapine-treated schizophrenia patients.
abstract: 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.
authors.affiliation: Schizophrenia Program, Massachusetts General Hospital, Boston, MA, USA. dchenderson@partners.org
authors.forename: David C
authors.initials: DC
authors.lastname: Henderson
authors.forename: Xiaoduo
authors.initials: X
authors.lastname: Fan
authors.forename: Paul M
authors.initials: PM
authors.lastname: Copeland
authors.forename: Bikash
authors.initials: B
authors.lastname: Sharma
authors.forename: Christina P
authors.initials: CP
authors.lastname: Borba
authors.forename: Ryan
authors.initials: R
authors.lastname: Boxill
authors.forename: Oliver
authors.initials: O
authors.lastname: Freudenreich
authors.forename: Corinne
authors.initials: C
authors.lastname: Cather
authors.forename: A Eden
authors.initials: AE
authors.lastname: Evins
authors.forename: Donald C
authors.initials: DC
authors.lastname: Goff
mesh_terms: 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
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D014280:Triglycerides; D001569:Benzodiazepines; D000068180:Aripiprazole; D002097:C-Reactive Protein; D002784:Cholesterol; D005947:Glucose; D000077152:Olanzapine