title: Leptin concentrations are increased in subjects treated with clozapine or conventional antipsychotics.
abstract: BACKGROUND
  Overweight is a considerable clinical problem in patients treated with antipsychotic agents. Recent results suggest that insulin resistance with increased insulin levels is also associated with treatment with the atypical antipsychotic agent clozapine. Leptin is important for the control of body weight and has been proposed to be a link between obesity and the insulin resistance syndrome. This study examined if clozapine-treated subjects and subjects treated with conventional antipsychotics had increased leptin levels compared with the general population and whether there was a gender difference in this respect.
  
  
  METHODS
  Clozapine-treated patients (N = 41), patients treated with conventional antipsychotic drugs (N = 62), and healthy subjects from the Northern Sweden Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) project (N = 189) were investigated with a cross-sectional study design. Weight, body mass index (BMI), and plasma leptin concentrations were measured, and all study subjects were investigated for the presence of diabetes mellitus. Drug treatment, health status, and smoking habits were registered.
  
  
  RESULTS
  After adjustment for gender, BMI, smoking habits, age, and diabetes, hyperleptinemia was independently (p < .001) associated with clozapine treatment and with treatment with conventional antipsychotics (p < .005) within a multiple regression analysis. In separate multiple regression analyses, leptin levels were significantly associated with clozapine treatment in men (p = .002) and women (p =.023) and with conventional antipsychotic treatment in men (p = .027) but not in women.
  
  
  CONCLUSIONS
  Treatment with clozapine as well as with conventional antipsychotics is associated with increased levels of circulating leptin. Hyperleptinemia can be an important link in the development of overweight and the insulin resistance syndrome in subjects receiving antipsychotic drugs, especially atypical agents like clozapine.
authors.affiliation: Division of Clinical Pharmacology, Norrland University Hospital, Umeå, Sweden. staffan.hagg@pharm.umu.se
authors.forename: S
authors.initials: S
authors.lastname: Hägg
authors.forename: S
authors.initials: S
authors.lastname: Söderberg
authors.forename: B
authors.initials: B
authors.lastname: Ahrén
authors.forename: T
authors.initials: T
authors.lastname: Olsson
authors.forename: T
authors.initials: T
authors.lastname: Mjörndal
mesh_terms: D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D015992:Body Mass Index; D003024:Clozapine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D003430:Cross-Sectional Studies; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood; D020738:Leptin / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000139:chemically induced; D011618:Psychotic Disorders / Q000188:drug therapy*; D011863:Radioimmunoassay
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D020738:Leptin; D003024:Clozapine