Effect of Atypical Antipsychotic Drugs Olanzapine and Amisulpride on Glucose Metabolism

Effects of the Serotonin 2A Receptor on Insulin Sensitivity and Secretion: a Double-blind Controlled Comparison of Olanzapine vs. Amisulpride:

Patients suffering from schizophrenia have a high risk to become obese and develop diabetes. Risk of obesity is particularly high with some newer schizophrenia drugs, such as clozapine or olanzapine. These drugs are called atypical drugs and exert their action in part by occupying receptors for serotonin, particularly the 5HT2A receptor subtype. This receptor may also interfere with glucose metabolism and insulin action. The purpose of this study is to compare an atypical antipsychotic drugs, olanzapine, which acts by occupying the 5HT2A receptor, to another antipsychotic drug, amisulpride, which mainly acts through the dopamine pathway. Healthy volunteers are recruited and asked to take a single dose of each drug and of placebo on separate days. Then, a combined glucose clamp study will be performed in order to test the effects of these drugs on insulin sensitivity and insulin secretion.

10 male healthy volunteers are recruited. After informed consent, they are admitted to the study ward at 10:00 p.m. prior to the study day and kept fasting until the next morning. At 8:00 a.m. they receive their study medication (olanzapine, amisulpride or placebo). Subsequently, measurements of insulin sensitivity and insulin secretion are performed by euglycemic hyperinsulinemic clamp technique followed by hyperglycemic clamp.

schizophrenia, olanzapine, atypical antipsychotic drugs, amisulpride, diabetes, insulin resistance, insulin secretion, glucose, euglycemic hyperinsulinemic clamp, hyperglycemic clamp

euglycemic hyperinsulinemic clamp with target blood glucose of 90 mg/dl (5 mmol/l), followed by hyperglycemic clamp, target blood glucose of 180 mg/dl (10 mmol/l) for measurement of insulin sensitivity and insulin secretion

C-peptide measured 4 times during hyperglycemic clamp period at time 0 min (prior to glucose bolus), 5 min, 10 min and 60 min after glucose bolus

Inclusion Criteria: healthy male volunteers written informed consent Exclusion Criteria: BMI > 30 kg/m² Diabetes mellitus Hypertension Treatment with drugs interfering with lipid or glucose metabolism (e.g. statins, oral antidiabetic drugs, glucocorticoids) History of seizures