title: 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.
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 > or =3 months and had experienced weight gain of > or =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/m(2)) 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.
authors.affiliation: Biological Psychiatry Division, Medical University Innsbruck, Innsbruck, Austria. wolfgang.fleischhacker@i-med.ac.at
authors.forename: W Wolfgang
authors.initials: WW
authors.lastname: Fleischhacker
authors.forename: Martti E
authors.initials: ME
authors.lastname: Heikkinen
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Olié
authors.forename: Wally
authors.initials: W
authors.lastname: Landsberg
authors.forename: Patricia
authors.initials: P
authors.lastname: Dewaele
authors.forename: Robert D
authors.initials: RD
authors.lastname: McQuade
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Loze
authors.forename: Delphine
authors.initials: D
authors.lastname: Hennicken
authors.forename: Wendy
authors.initials: W
authors.lastname: Kerselaers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000068180:Aripiprazole; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects* / Q000502:physiology; D017024:Chemotherapy, Adjuvant; D002784:Cholesterol / Q000097:blood; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D015363:Quinolones / Q000627:therapeutic use*; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole; D002784:Cholesterol; D003024:Clozapine