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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00625170

Enrollment

Registered

2008-02-28

Start date

2004-05-31

Completion date

2004-12-31

Last updated

2008-02-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Dyslipidemia, Insulin Resistance

Keywords

Antipsychotics, Olanzapine, Haloperidol, Insulin resistance, Dyslipidemia

Brief summary

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.

Interventions

DRUGolanzapine

olanzapine 10 mg/day for 8 days

DRUGHaloperidol

haloperidol 3 mg/day for 8 days

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Masking

SINGLE (Subject)

Eligibility

Sex/Gender

MALE

Age

20 Years to 40 Years

Healthy volunteers

Yes

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)

Design outcomes

Primary

Measure	Time frame
To determine the effect of subchronic olanzapine and haloperidol treatment on HGO, whole body peripheral glucose disposal, fatty acid flux and fuel oxidation.	8 days

Countries

Netherlands

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026