title: Different influences of classical antipsychotics and clozapine on glucose-insulin homeostasis in patients with schizophrenia or related psychoses.
abstract: BACKGROUND
  The aim of this study was to investigate the influence of classical antipsychotics and the atypical antipsychotic agent clozapine on glucose-insulin homeostasis to explain possible mechanisms behind weight gain associated with antipsychotic treatment.
  
  
  METHODS
  Twenty-eight patients on therapy with classical antipsychotics and 13 patients treated with clozapine (all meeting DSM-III-R criteria for schizophrenia or related psychoses) were studied. Fasting blood samples for glucose and insulin, as well as for 2 markers of the glucose-insulin homeostasis, i.e., the growth hormone (GH)-dependent insulin-like growth factor I (IGF-I) and the insulin-dependent insulin-like growth factor binding protein-1, were analyzed. Body mass index (BMI) was calculated and serum concentrations of the different antipsychotic drugs were measured. In addition, the relationship between the endocrine parameters and drug serum concentrations was examined.
  
  
  RESULTS
  The insulin levels were positively correlated to the serum concentration of clozapine, whereas no correlations were found between insulin and the serum concentrations of perphenazine (N = 12) or zuclopenthixol (N = 9). Insulin elevation was seen in the patients receiving clozapine more frequently than in the patients receiving classical antipsychotics. In addition, the median level of IGF-I was significantly lower in the patients receiving clozapine than in the patients receiving classical antipsychotics. No significant difference in BMI was found between the 2 patient groups, and all patients but 1 were normoglycemic.
  
  
  CONCLUSIONS
  The correlation between insulin and the clozapine concentration indicates a probable influence of clozapine on insulin secretion. The normal blood glucose levels in the clozapine group support the theory that clozapine induces concentration-dependent insulin resistance with secondary increased insulin secretion. In addition, lower median level of IGF-I in patients receiving clozapine compared with patients receiving classical antipsychotics points to a lower GH secretion in the clozapine group. This impaired GH secretion together with the clozapine-induced insulin resistance might be mechanisms behind weight gain during clozapine therapy.
authors.affiliation: Department of Psychiatry, St. Görans Hospital, Stockholm, Sweden.
authors.forename: K I
authors.initials: KI
authors.lastname: Melkersson
authors.forename: A L
authors.initials: AL
authors.lastname: Hulting
authors.forename: K E
authors.initials: KE
authors.lastname: Brismar
mesh_terms: D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis* / Q000187:drug effects; D015992:Body Mass Index; D003024:Clozapine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000097:blood* / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D001786:Blood Glucose; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I; D003024:Clozapine