title: Differential effects of olanzapine and risperidone on plasma adiponectin levels over time: results from a 3-month prospective open-label study.
abstract: Second-generation antipsychotics (SGA), especially clozapine and olanzapine, are associated with an increased metabolic risk. Recent research showed that plasma adiponectin levels, an adipocyte-derived hormone that increases insulin sensitivity, vary in the same way in schizophrenic patients as in the general population according to gender, adiposity and metabolic syndrome (MetS). The aim of the present study was to investigate whether different SGAs differentially affect plasma adiponectin levels independent of body mass index (BMI) and MetS status. 113 patients with schizophrenia (65.5% males, 32.3years old) who were free of antipsychotic medication were enrolled in this open-label prospective single-center study and received either risperidone (n=54) or olanzapine (n=59). They were followed prospectively for 12weeks. Average daily dose was 4.4mg/day for risperidone and 17.4mg/day for olanzapine. Plasma adiponectin levels as well as fasting metabolic parameters were measured at baseline, 6weeks and 12weeks. The two groups had similar baseline demographic and metabolic characteristics. A significant increase in body weight was observed over time. This increase was significantly larger in the olanzapine group than in the risperidone group (+7.0kg versus +3.1kg, p<0.0002). Changes in fasting glucose and insulin levels and in HOMA-IR, an index of insulin resistance, were not significantly different in both treatment groups. MetS prevalence increased significantly more in the olanzapine group as compared to the risperidone groups where the prevalence did not change over time. We observed a significant (p=0.0015) treatment by time interaction showing an adiponectin increase in the risperidone-treated patients (from 10,154 to 11,124ng/ml) whereas adiponectin levels decreased in olanzapine treated patients (from 11,280 to 8988ng/ml). This effect was independent of BMI and the presence/absence of MetS. The differential effect of antipsychotic treatment (risperidone versus olanzapine) on plasma adiponectin levels over time, independent of changes in waist circumference and antipsychotic dosing, suggests a specific effect on adipose tissues, similar to what has been observed in animal models. The observed olanzapine-associated reduction in plasma adiponectin levels may at least partially contribute to the increased metabolic risk of olanzapine compared to risperidone.
authors.affiliation: University Psychiatric Centre Catholic University Leuven, Campus Kortenberg, Kortenberg, Belgium.
authors.forename: Martien
authors.initials: M
authors.lastname: Wampers
authors.forename: Linda
authors.initials: L
authors.lastname: Hanssens
authors.forename: Ruud
authors.initials: R
authors.lastname: van Winkel
authors.forename: Adrian
authors.initials: A
authors.lastname: Heald
authors.forename: Julien
authors.initials: J
authors.lastname: Collette
authors.forename: Joseph
authors.initials: J
authors.lastname: Peuskens
authors.forename: Jean Yves
authors.initials: JY
authors.lastname: Reginster
authors.forename: Andre
authors.initials: A
authors.lastname: Scheen
authors.forename: Marc
authors.initials: M
authors.lastname: De Hert
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000494:pharmacology / Q000627:therapeutic use*; D015992:Body Mass Index; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011446:Prospective Studies; D018967:Risperidone / Q000494:pharmacology / Q000627:therapeutic use*; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D055105:Waist Circumference / Q000187:drug effects
chemical_list: D052242:Adiponectin; D014150:Antipsychotic Agents; D001569:Benzodiazepines; D018967:Risperidone; D000077152:Olanzapine