The International Journal of Neuropsychopharmacology

Table of Contents - 2010 - Volume 13, Issue 08 (Thematic Section: Memory and Cognition)  

Research Article

Effects of adjunctive treatment with aripiprazole on body weight and clinical efficacy in schizophrenia patients treated with clozapine: a randomized, double-blind, placebo-controlled trial

W. Wolfgang Fleischhackera1 c1, Martti E. Heikkinena2, Jean-Pierre Oliéa3, Wally Landsberga4, Patricia Dewaelea5, Robert D. McQuadea6, Jean-Yves Lozea7, Delphine Hennickena5 and Wendy Kerselaersa5

a1 Biological Psychiatry Division, Medical University Innsbruck, Innsbruck, Austria

a2 Helsinki City Health Centre, Department of Psychiatry, Community Mental Health Services, Helsinki, Finland

a3 Hopital Saint Anne, Paris, France

a4 Bristol–Myers Squibb Company, Paris, France

a5 Bristol–Myers Squibb Company, Braine l'Alleud, Belgium

a6 Otsuka Pharmaceutical Development and Commercialization Inc., Princeton, NJ, USA

a7 Otsuka Pharmaceuticals France, Paris, France

Abstract

Clozapine is associated with significant weight gain and metabolic disturbances. This multicentre, randomized study comprised a double-blind, placebo-controlled treatment phase of 16 wk, and an open-label extension phase of 12 wk. Outpatients who met DSM-IV-TR criteria for schizophrenia, who were not optimally controlled while on stable dosage of clozapine for ⩾3 months and had experienced weight gain of ⩾2.5 kg while taking clozapine, were randomized (n=207) to aripiprazole at 5–15 mg/d or placebo, in addition to a stable dose of clozapine. The primary endpoint was mean change from baseline in body weight at week 16 (last observation carried forward). Secondary endpoints included clinical efficacy, body mass index (BMI) and waist circumference. A statistically significant difference in weight loss was reported for aripiprazole vs. placebo (−2.53 kg vs. −0.38 kg, respectively, difference=−2.15 kg, p<0.001). Aripiprazole-treated patients also showed BMI (median reduction 0.8 kg/m2) and waist circumference reduction (median reduction 2.0 cm) vs. placebo (no change in either parameter, p<0.001 and p=0.001, respectively). Aripiprazole-treated patients had significantly greater reductions in total and low-density lipoprotein (LDL) cholesterol. There were no significant differences in Positive and Negative Syndrome Scale total score changes between groups but Clinical Global Impression Improvement and Investigator's Assessment Questionnaire scores favoured aripiprazole over placebo. Safety and tolerability were generally comparable between groups. Combining aripiprazole and clozapine resulted in significant weight, BMI and fasting cholesterol benefits to patients suboptimally treated with clozapine. Improvements may reduce metabolic risk factors associated with clozapine treatment.

(Received October 28 2009)

(Reviewed January 27 2010)

(Revised March 23 2010)

(Accepted April 02 2010)

(Online publication May 12 2010)

Key Words:

Correspondence:

c1 Address for correspondence: W. W. Fleischhacker, Biological Psychiatry Division, Medical University Innsbruck, Innsbruck, Austria. Tel.: +43 512 504 23669 Fax: +43 512 504 25267 E-mail:wolfgang.fleischhacker@i-med.ac.at

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