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DURHAM, N.C. – Research from Duke University Medical Center
suggests there might be a link between at least one drug used
to treat schizophrenia
and the onset of diabetes, a disease widely recognized as one
of the leading causes of death and disability in the U.S.

The drug, olanzapine (trade name Zyprexa), belongs to a relatively
new family of medications called atypical antipsychotics, which
are used to treat schizophrenia, paranoia and manic-depressive
disorders. Other drugs in this class include clozapine,
risperidone, quetiapine and ziprasidone.

The researchers found metabolic abnormalities ranging from
mild blood sugar problems to diabetic ketoacidosis and coma in
patients who had been prescribed olanzapine, most of whom were
otherwise not known to be diabetic. Diabetic ketoacidosis (DKA)
is a serious condition in which a person experiences an extreme
rise in blood glucose level coupled with a severe lack of
insulin, which results in symptoms such as nausea, vomiting,
stomach pain and rapid breathing. Untreated, DKA can lead to
coma and even death.

"While our report does not prove a causal relationship
between the drug and diabetes, doctors should be aware of such
potentially adverse effects," said P. Murali Doraiswamy, M.D.,
a psychiatrist at Duke and co-author of the study. "We've found
cases where patients had some very serious problems associated
with olanzapine, and at least 23 of them died."

The findings appear in the July 2, 2002 issue of
Pharmacotherapy. The research was self-supported by the
authors.

Doraiswamy and Elizabeth A. Koller, M.D., lead author of the
study and a medical officer at the FDA, queried the FDA MedWatch Drug Surveillance
System, MEDLINE (a biomedical database) and selected
abstracts from national psychiatry meetings over a period of
eight years and identified 289 cases of diabetes in patients
who had been given olanzapine. Of the 289 cases of diabetes
linked to the use of olanzapine, 225 were newly diagnosed
cases. One hundred patients developed ketosis (a serious
complication of diabetes), and 22 people developed
pancreatitis, or inflammation of the pancreas, which is a
life-threatening condition. There were 23 deaths, including
that of a 15-year-old adolescent who died of necrotizing
pancreatitis, a condition where the pancreas breaks down and
dies. Most cases (71 percent) occurred within six months of
starting the drug and many cases were associated with moderate
weight gain.

"The average age of adults showing signs of diabetes after
taking olanzapine was about 10 years younger than what is
generally seen in the community," said Doraiswamy. "The younger
age at onset plus the number of serious complications and the
improvements reported when the drug was stopped all suggest a
link to the disease. However, until we know if there are risk
differences among drugs in this class, it is important for
physicians to watch all patients receiving this medication for
signs of diabetes so that it can be detected quickly and
managed."

The study merely suggests an association between the drug
and diabetes, said Doraiswamy. Further studies are needed to
offer more conclusive evidence of a direct causal relationship.
If future studies confirm the findings, he said that perhaps
the FDA should consider including a stronger warning label for
these drugs.

"The numbers are still sketchy since many adverse reactions
are not reported to the FDA and we don't have a good handle on
how many people have actually received these drugs," he
cautioned. "Atypical antipsychotics can be life saving
medications, but we need to learn more about their long-term
side-effects. I think this should be a high priority for
investigation."

Doraiswamy was part of a team from Duke that first reported
a link between the antipsychotic drug clozapine and the
development of diabetes in a 1994 issue of the American Journal
of Psychiatry. Last year, Koller reported in the American
Journal of Medicine that the FDA had received 384 reports of
diabetes associated with the drug clozapine. According to the
researchers, many cases of diabetes have also been reported
with other antipsychotic drugs.

Doraiswamy has previously received funding and consulting
fees from all companies that currently manufacture
antipsychotic medications, including Eli Lilly and Company, the
manufacturer of Zyprexa.