Elevated Levels of Insulin, Leptin, and Blood Lipids in Olanzapine-Treated Patients With Schizophrenia or Related Psychoses

Background: The aim of this study was toinvestigate the influence of the antipsychotic agent olanzapineon glucose-insulin homeostasis to explain possible mechanismsbehind olanzapine-associated weight gain.

Method: Fourteen patients on treatment witholanzapine (all meeting DSM-IV criteria for schizophrenia orrelated psychoses) were studied. Fasting blood samples forglucose, insulin, the growth hormone (GH)-dependent insulin-likegrowth factor I, and the insulin-dependent insulin-like growthfactor binding protein-1 (IGFBP-1) were analyzed, as well as GH,leptin, and blood lipid levels and the serum concentrations ofolanzapine and its metabolite N-desmethylolanzapine. Inaddition, body mass index (BMI) was calculated. Moreover, weightchange during olanzapine treatment was determined.

Results: Twelve of the 14 patients reportedweight gain between 1 and 10 kg during a median olanzapinetreatment time of 5 months, whereas data were not available forthe other 2 patients. Eight patients (57%) had BMI above thenormal limit. Eleven patients were normoglycemic, and 3 showedincreased blood glucose values. Most patients (10/14; 71%) hadelevated insulin levels (i.e., above the normal limit).Accordingly, the median value of IGFBP-1 was significantly lowerfor the patients in comparison with healthy subjects. Moreover, 8(57%) of 14 patients had hyperleptinemia, 62% (8/13) hadhypertriglyceridemia, and 85% (11/13) hypercholesterolemia.Weight change correlated positively to blood glucose levels andinversely to the serum concentration level of N-desmethylolanzapine.Additionally, the levels of blood glucose, triglycerides, andcholesterol correlated inversely to the serum concentration of N-desmethylolanzapine.

Conclusion: Olanzapine treatment was associatedwith weight gain and elevated levels of insulin, leptin, andblood lipids as well as insulin resistance, with 3 patientsdiagnosed to have diabetes mellitus. Both increased insulinsecretion and hyprleptinemia may be mechanisms behindolanzapine-induced weight gain. Moreover, it is suggested thatthe metabolite N-desmethylolanzapine, but not olanzapine,has a normalizing effect on the metabolic abnormalities.