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A Double Blind, Placebo-Controlled, Randomized Crossover Study of the Acute Metabolic Effects of Olanzapine in Healthy Volunteers

BACKGROUND AND RATIONALE: Atypical antipsychotics exhibit metabolic side effects including diabetes mellitus and obesity. The adverse events are preceded by acute worsening of oral glucose tolerance (oGTT) along with reduced plasma free fatty acids (FFA) and leptin in animal models. It is unclear wh...

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Autores principales: Albaugh, Vance L., Singareddy, Ravi, Mauger, David, Lynch, Christopher J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153475/
https://www.ncbi.nlm.nih.gov/pubmed/21857944
http://dx.doi.org/10.1371/journal.pone.0022662
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author Albaugh, Vance L.
Singareddy, Ravi
Mauger, David
Lynch, Christopher J.
author_facet Albaugh, Vance L.
Singareddy, Ravi
Mauger, David
Lynch, Christopher J.
author_sort Albaugh, Vance L.
collection PubMed
description BACKGROUND AND RATIONALE: Atypical antipsychotics exhibit metabolic side effects including diabetes mellitus and obesity. The adverse events are preceded by acute worsening of oral glucose tolerance (oGTT) along with reduced plasma free fatty acids (FFA) and leptin in animal models. It is unclear whether the same acute effects occur in humans. METHODOLOGY/PRINCIPAL FINDINGS: A double blind, randomized, placebo-controlled crossover trial was conducted to examine the potential metabolic effects of olanzapine in healthy volunteers. Participants included male (8) and female (7) subjects [18–30 years old, BMI 18.5–25]. Subjects received placebo or olanzapine (10 mg/day) for three days prior to oGTT testing. Primary endpoints included measurement of plasma leptin, oral glucose tolerance, and plasma free fatty acids (FFA). Secondary metabolic endpoints included: triglycerides, total cholesterol, high- and low-density lipoprotein cholesterol, heart rate, blood pressure, body weight and BMI. Olanzapine increased glucose Area Under the Curve (AUC) by 42% (2808±474 vs. 3984±444 mg/dl·min; P = 0.0105) during an oGTT. Fasting plasma leptin and triglycerides were elevated 24% (Leptin: 6.8±1.3 vs. 8.4±1.7 ng/ml; P = 0.0203) and 22% (Triglycerides: 88.9±10.1 vs. 108.2±11.6 mg/dl; P = 0.0170), whereas FFA and HDL declined by 32% (FFA: 0.38±0.06 vs. 0.26±0.04 mM; P = 0.0166) and 11% (54.2±4.7 vs. 48.9±4.3 mg/dl; P = 0.0184), respectively after olanzapine. Other measures were unchanged. CONCLUSIONS/SIGNIFICANCE: Olanzapine exerts some but not all of the early endocrine/metabolic changes observed in rodent models of the metabolic side effects, and this suggest that antipsychotic effects are not limited to perturbations in glucose metabolism alone. Future prospective clinical studies should focus on identifying which reliable metabolic alterations might be useful as potential screening tools in assessing patient susceptibility to weight gain and diabetes caused by atypical antipsychotics. TRIAL REGISTRATION: ClinicalTrials.gov NCT00741026
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spelling pubmed-31534752011-08-19 A Double Blind, Placebo-Controlled, Randomized Crossover Study of the Acute Metabolic Effects of Olanzapine in Healthy Volunteers Albaugh, Vance L. Singareddy, Ravi Mauger, David Lynch, Christopher J. PLoS One Research Article BACKGROUND AND RATIONALE: Atypical antipsychotics exhibit metabolic side effects including diabetes mellitus and obesity. The adverse events are preceded by acute worsening of oral glucose tolerance (oGTT) along with reduced plasma free fatty acids (FFA) and leptin in animal models. It is unclear whether the same acute effects occur in humans. METHODOLOGY/PRINCIPAL FINDINGS: A double blind, randomized, placebo-controlled crossover trial was conducted to examine the potential metabolic effects of olanzapine in healthy volunteers. Participants included male (8) and female (7) subjects [18–30 years old, BMI 18.5–25]. Subjects received placebo or olanzapine (10 mg/day) for three days prior to oGTT testing. Primary endpoints included measurement of plasma leptin, oral glucose tolerance, and plasma free fatty acids (FFA). Secondary metabolic endpoints included: triglycerides, total cholesterol, high- and low-density lipoprotein cholesterol, heart rate, blood pressure, body weight and BMI. Olanzapine increased glucose Area Under the Curve (AUC) by 42% (2808±474 vs. 3984±444 mg/dl·min; P = 0.0105) during an oGTT. Fasting plasma leptin and triglycerides were elevated 24% (Leptin: 6.8±1.3 vs. 8.4±1.7 ng/ml; P = 0.0203) and 22% (Triglycerides: 88.9±10.1 vs. 108.2±11.6 mg/dl; P = 0.0170), whereas FFA and HDL declined by 32% (FFA: 0.38±0.06 vs. 0.26±0.04 mM; P = 0.0166) and 11% (54.2±4.7 vs. 48.9±4.3 mg/dl; P = 0.0184), respectively after olanzapine. Other measures were unchanged. CONCLUSIONS/SIGNIFICANCE: Olanzapine exerts some but not all of the early endocrine/metabolic changes observed in rodent models of the metabolic side effects, and this suggest that antipsychotic effects are not limited to perturbations in glucose metabolism alone. Future prospective clinical studies should focus on identifying which reliable metabolic alterations might be useful as potential screening tools in assessing patient susceptibility to weight gain and diabetes caused by atypical antipsychotics. TRIAL REGISTRATION: ClinicalTrials.gov NCT00741026 Public Library of Science 2011-08-09 /pmc/articles/PMC3153475/ /pubmed/21857944 http://dx.doi.org/10.1371/journal.pone.0022662 Text en Albaugh et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Albaugh, Vance L.
Singareddy, Ravi
Mauger, David
Lynch, Christopher J.
A Double Blind, Placebo-Controlled, Randomized Crossover Study of the Acute Metabolic Effects of Olanzapine in Healthy Volunteers
title A Double Blind, Placebo-Controlled, Randomized Crossover Study of the Acute Metabolic Effects of Olanzapine in Healthy Volunteers
title_full A Double Blind, Placebo-Controlled, Randomized Crossover Study of the Acute Metabolic Effects of Olanzapine in Healthy Volunteers
title_fullStr A Double Blind, Placebo-Controlled, Randomized Crossover Study of the Acute Metabolic Effects of Olanzapine in Healthy Volunteers
title_full_unstemmed A Double Blind, Placebo-Controlled, Randomized Crossover Study of the Acute Metabolic Effects of Olanzapine in Healthy Volunteers
title_short A Double Blind, Placebo-Controlled, Randomized Crossover Study of the Acute Metabolic Effects of Olanzapine in Healthy Volunteers
title_sort double blind, placebo-controlled, randomized crossover study of the acute metabolic effects of olanzapine in healthy volunteers
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153475/
https://www.ncbi.nlm.nih.gov/pubmed/21857944
http://dx.doi.org/10.1371/journal.pone.0022662
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