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. METHOD: 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. CONCLUSION: 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.
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. METHOD: 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. CONCLUSION: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.
Authors: Benjamin U Nwosu; Bruce Meltzer; Louise Maranda; Carol Ciccarelli; Daniel Reynolds; Laura Curtis; Jean King; Jean A Frazier; Mary M Lee Journal: J Pediatr Endocrinol Metab Date: 2011 Impact factor: 1.634
Authors: R Coccurello; A Caprioli; O Ghirardi; R Conti; B Ciani; S Daniele; A Bartolomucci; A Moles Journal: Psychopharmacology (Berl) Date: 2006-05-13 Impact factor: 4.530
Authors: Mikhail Kalinichev; Claire Rourke; Alex J Daniels; Mary K Grizzle; Christy S Britt; Diane M Ignar; Declan N C Jones Journal: Psychopharmacology (Berl) Date: 2005-10-19 Impact factor: 4.530