Metabolic Effects of Subchronic Dopamine D2 Receptor Blockade by Antipsychotic Drugs in Healthy Humans

Leiden University Medical Center (LUMC)

Status

Completed

Conditions

Insulin Resistance

Dyslipidemia

Treatments

Drug: olanzapine

Drug: Haloperidol

Study type

Interventional

Funder types

Other

Identifiers

NCT00625170

P03.136

Details and patient eligibility

About

We hypothesized that short-term treatment with AP drugs induces insulin resistance through a mechanistic route that is independent of weight gain and that atypical drugs exert stronger effects than typical compounds in this respect. We therefore treated healthy non-obese men with olanzapine (atypical AP) or haloperidol (typical AP) for 8 days, and studied the impact of these interventions on glucose and lipid metabolism by hyperinsulinemic euglycemic clamp, isotope dilution technology and indirect calorimetry.

Enrollment

11 patients

Sex

Male

Ages

20 to 40 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Healthy men, with and without a positive family history of schizophrenia.
20 kg/m2 < BMI < 26 kg/m2
Age 20-40 years
Fasting plasma glucose < 6 mmo/L

Exclusion criteria

FPG > 6 mmol/L
BMI > 26 kg/m2
Psychiatric disorders and/or use of antipsychotic or antidepressants drugs at present or in the past.
Any significant chronic disease
Renal, hepatic or endocrine disease
Use of medication known to influence lipolysis and/or glucose metabolism
Total cholesterol > 7mmol/L and/or triglycerides > 2 mmol/L
Recent weight changes or attempts to loose weight (> 3 kg weight gain or loss, within the last 3 months)
Difficulties to insert an intravenous catheter
Smoking (current)
Severe claustrophobia (ventilated hood)
Recent blood donation (within the last 2 months)
Recent participation in other research projects (within the last 3 months), participation in 2 or more projects in one year
Extensive sporting activities (more than 10 hours of exercise per week)