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Treatment With An
Antipsychotic Drug Found To Cause Changes In Metabolism
Earlier Than Expected
New study in male rats reveals
increases in problems associated with metabolic syndrome
SAN DIEGO, CA – Schizophrenia is a
complex type of psychotic mental illness characterized by thoughts that are
uncoupled from reality. Huge gains in the effective treatment of individuals
with the disease began in the 1950s with the development of the first
generation of antipsychotic drugs. The medications allowed physicians to
treat the “positive” effects of the illness (delusions and hallucinations)
and, to a lesser extent, the “negative” symptoms (apathy). The second
generation of antipsychotics – known as atypical antipsychotics (AAP) –
began in 1990. These newer medicines have proven as effective in treating
the positive aspects of the disease and more effective in combating the
negative ones.
As is the case with nearly all medications,
antipsychotics have side affects, including weight gain and some other risk
factors of metabolic syndrome, which puts an individual at greater risk of
heart disease and type 2 diabetes. Physicians are concerned that these side
effects may cause their patients to stop taking their medicine.
A team of French researchers has found, in an animal
model, that the consumption of at least one atypical antipsychotic exhibits
some of the risks for metabolic syndrome in humans. This model allows
researchers to explore the sequence of early metabolic events that may
result from atypical medications.
Presentation at the 121st Annual Meeting
of the American Physiological Society
Montserrat Victoriano, Gilles Fromentin, Jean-Francois
Huneau, and Dominique Hermier of the Department of Human Nutrition, INRA,
Paris, France; and Renaud de Beaurepaire, Department of Psychopharmacology,
Hospital Paul Guiraud, Villejuif, France, are the researchers. They have
conducted a study
entitled Energy Metabolism Disturbances Induced by Antipsychotic
Treatment in a Rat Model. Dr. Hermier will present the team’s findings
at the 121st annual meeting of the American Physiological Society
(APS;
www.the-APS.org/press), part of the Experimental Biology 2008 scientific
conference.
Summary of the Study
The researchers had previously developed a model for
antipsychotic-induced weight gain in the male rat, which allowed them to
clearly distinguish between those antipsychotic drugs that produce some
weight gain, moderate weight gain or no gain at all. These distinctions
corresponded to the response in humans. Their latest study is built on these
findings.
In the latest study they used 18 male rats which were
randomly assigned to one of three groups: (1) those receiving the
conventional antipsychotic drug haloperidol (HA); (2) those receiving the
atypical antipsychotic drug olanzapine (OL); or (3) the control (CO) group
which did not receive either drug. The medicines were given in food for a
period of six weeks. Female rats were excluded to eliminate bias in the
study since antipsychotic-induced weight gain in female rodents is likely
related to an interaction of the drugs with estrogens.
Testing after four weeks found that the concentration
of blood sugar (as glucose) was higher in OL rats (0.87 g/l) than in CO rats
(0.75 g/l) and the levels increased more rapidly after a glucose meal.
Testing six weeks later found fasting blood sugar levels continued to rise
in OL rats (1.46 g/l vs. 1.25 g/l in CO rats) while the level of lipids
(fats) in the blood was similar for both groups. Although there was no
difference in body weight gain or food intake, the proportion of fat stored
in the abdominal cavity was higher in OL rats (1.63%) vs. CO rats (1.44%).
The HA rats did not vary in any way with the control
group at any time. They exhibited a lower blood sugar level after a glucose
meal and a lower proportion of intraabdominal fat store (1.44%) than OL
rats.
Conclusions
Senior study author Dominique Hermier said, “Based on
these findings we concluded that male rats treated with olanzapine
experienced an early disruption of energy metabolism. This was a result of
the fat tissue we observed and the impairment in blood sugar regulation
which are both associated with metabolic syndrome and subsequent risk of
diabetes.”
She added, “Atypical medications like olanzapine are
of tremendous value in treating individuals with certain kinds of mental
illness. Our hope is that through discoveries such as this one, such
life-enhancing medicines can be further optimized.”
*****
Physiology is the study of how molecules, cells, tissues and organs
function to create health or disease. The American Physiological Society (APS;
www.The-APS.org/press) has been an integral part of this discovery
process since it was established in 1887.
# # #
NOTE TO EDITORS: The APS annual meeting is part
of the Experimental Biology 2008 (EB ’08) gathering and will be held April
5-9, 2008 at the San Diego, CA Convention Center. To schedule an interview
with Dr. Hermier please contact Donna Krupa at 301.634.7209 (office),
703.967.2751 (cell) or
DKrupa@the-APS.org.
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