Elevated levels of insulin, leptin, and blood lipids in olanzapine-treated patients with schizophrenia or related psychoses.
BACKGROUND
The aim of this study was to investigate the influence of the antipsychotic agent olanzapine on glucose-insulin homeostasis to explain possible mechanisms behind olanzapine-associated weight gain.


METHODS
Fourteen patients on treatment with olanzapine (all meeting DSM-IV criteria for schizophrenia or related psychoses) were studied. Fasting blood samples for glucose, insulin, the growth hormone (GH)-dependent insulin-like growth factor I, and the insulin-dependent insulin-like growth factor binding protein-1 (IGFBP-1) were analyzed, as well as GH, leptin, and blood lipid levels and the serum concentrations of olanzapine and its metabolite N-desmethylolanzapine. In addition, body mass index (BMI) was calculated. Moreover, weight change during olanzapine treatment was determined.


RESULTS
Twelve of the 14 patients reported weight gain between 1 and 10 kg during a median olanzapine treatment time of 5 months, whereas data were not available for the other 2 patients. Eight patients (57%) had BMI above the normal limit. Eleven patients were normoglycemic, and 3 showed increased blood glucose values. Most patients (10/14; 71%) had elevated insulin levels (i.e., above the normal limit). Accordingly, the median value of IGFBP-1 was significantly lower for the patients in comparison with healthy subjects. Moreover, 8 (57%) of 14 patients had hyperleptinemia, 62% (8/13) had hypertriglyceridemia, and 85% (11/13) hypercholesterolemia. Weight change correlated positively to blood glucose levels and inversely to the serum concentration level of N-desmethylolanzapine. Additionally, the levels of blood glucose, triglycerides, and cholesterol correlated inversely to the serum concentration of N-desmethylolanzapine.


CONCLUSIONS
Olanzapine treatment was associated with weight gain and elevated levels of insulin, leptin, and blood lipids as well as insulin resistance, with 3 patients diagnosed to have diabetes mellitus. Both increased insulin secretion and hyprleptinemia may be mechanisms behind olanzapine-induced weight gain. Moreover, it is suggested that the metabolite N-desmethylolanzapine, but not olanzapine, has a normalizing effect on the metabolic abnormalities.
Melkersson
K I
KI
Department of Psychiatry, St Görans Hospital, Stockholm, Sweden.
Hulting
A L
AL
Brismar
K E
KE
D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood / Q000627:therapeutic use*; D001569:Benzodiazepines; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood*; D020738:Leptin / Q000097:blood*; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use*; D011618:Psychotic Disorders / Q000097:blood* / Q000188:drug therapy*; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy*; D014280:Triglycerides / Q000097:blood
D014150:Antipsychotic Agents; D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D008055:Lipids; D014280:Triglycerides; D001569:Benzodiazepines; D010890:Pirenzepine; D000077152:Olanzapine