Acute effects of single-dose olanzapine on metabolic, endocrine, and inflammatory markers in healthy controls.

Abstract

Atypical antipsychotics may "directly" influence glucose homeostasis, increasing risk of type 2 diabetes independently of changes in adiposity. Animal models suggest direct effects after even a single dose of certain atypical antipsychotics on glucose dysregulation. Here, we investigated effects of a single-dose olanzapine (OLA) on glucose metabolism in healthy volunteers, thereby minimizing confounding effects of the illness of schizophrenia and adiposity. In a randomized double-blind crossover design, 15 subjects were administered 10 mg of OLA or placebo at 7:00 A.M. on separate study dates. A frequently sampled intravenous glucose tolerance test was initiated 4.25 hours later to assess changes in glucose homeostasis, including an index of insulin sensitivity, disposition index, glucose effectiveness, and acute insulin response to glucose. We also examined effects on cortisol, prolactin, fasting free fatty acids (FFAs), insulin-mediated suppression of FFAs, and adipocytokines (leptin, adiponectin, C-reactive protein, interleukin 6, and tumor necrosis factor α). Complete data for both visits were analyzed for 12 subjects. Olanzapine treatment significantly decreased glucose effectiveness (P = 0.041) and raised fasting glucose over 4.25 hours (P = 0.03) as compared to placebo. Olanzapine was associated with lower serum cortisol (P = 0.003), lower fasting FFA (P = 0.042), and increased prolactin levels (P < 0.0001). We therefore suggest that a single dose of OLA may invoke early changes in some parameters of glucose and lipid metabolism, as well as endocrine indices.

• Authors: Margaret Karolina Hahn, Tom M S Wolever, Tamara Arenovich, Celine Teo, Adria Giacca, Valerie Powell, Leigh Clarke, Paul Fletcher, Tony Cohn, Roger S McIntyre, Sylvia Gomes, Araba Chintoh, Gary J Remington
• Journal: Journal of clinical psychopharmacology (J Clin Psychopharmacol) Vol. 33 Issue 6 Pg. 740-6 (Dec 2013) ISSN: 1533-712X [Electronic] United States
• PMID: 24100786 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Adipokines
• Antipsychotic Agents
• Blood Glucose
• Fatty Acids, Nonesterified
• Insulin
• Benzodiazepines
• Prolactin
• Olanzapine
• Hydrocortisone

Topics

• Adipokines (metabolism)
• Adult
• Antipsychotic Agents (pharmacology)
• Benzodiazepines (pharmacology)
• Blood Glucose (drug effects)
• Cross-Over Studies
• Double-Blind Method
• Fatty Acids, Nonesterified (metabolism)
• Female
• Glucose Tolerance Test
• Humans
• Hydrocortisone (blood)
• Insulin (metabolism)
• Insulin Resistance
• Lipid Metabolism (drug effects)
• Male
• Olanzapine
• Prolactin (metabolism)