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TUESDAY, Nov. 27 (HealthScoutNews) -- New
research warns doctors who treat adolescents for
schizophrenia and other psychotic illnesses to
watch closely for signs of blood sugar trouble.
Scientists have found that a class of widely
used antipsychotic medications significantly
increases the risk of hyperglycemia, a dangerous
surge in blood glucose. The findings, from
researchers at Duke University and the Food and
Drug Administration (FDA), appear as a letter in
the Nov. 28 issue of the Journal of the American
Medical Association.
The research involves a relatively new family
of compounds called atypical antipsychotics,
which include clozapine and its newer cousin,
olanzapine. These drugs have long been known to
promote weight gain and increase the risk of
diabetes, or fan a smoldering case, although
experts don't know why.
A paper this year in a Journal of Clinical
Psychiatry supplement reports the FDA has been
alerted to more than 140 cases of new-onset
diabetes in patients taking clozapine. Three
dozen cases involved ketoacidosis, a potentially
deadly complication of elevated blood sugar. The
paper also cited 19 case reports of diabetes
associated with the use of olanzapine, sold as
Zyprexa by Indianapolis-based Eli Lilly and Co.
But the problem hasn't been studied among
patients in adolescence, when symptoms of some
psychotic diseases, particularly schizophrenia,
usually appear.
In the new research, Dr. Elizabeth Koller, an
FDA medical officer, and colleagues culled the
agency's MedWatch database for blood sugar
trouble associated with clozapine and olanzapine.
They found 11 reports of runaway blood sugar
in patients ages 13 to 18 taking clozapine
between January 1993 and March last year. They
also found nine reports of similar complications
among teens taking olanzapine between January
1996 and May 2001.
Of the patients on olanzapine, seven had
newly diagnosed hyperglycemia while two already
were identified as diabetics. The sugar disorder
developed within a week of taking the drug in
two patients and within six months for eight
others. (Data are missing for the ninth.)
Sugar control improved in four patients who
stopped taking the drug or scaled back their
dose. But one patient ultimately died of
necrotizing pancreatitis, a condition in which
cells in the pancreas die.
One youth taking clozapine also developed
pancreatitis more than a month after stopping
the drug. That patient survived.
Available information showed that eight of
the clozapine patients with high blood sugar
never had the problem before. Although the
patients on olanzapine also were taking a wide
range of other medications, those on clozapine
took only one other medication.
Though diabetes linked to obesity is a
growing problem among American teens, it is
uncommon enough -- one case per 1,000 people
under age 25 -- that uncontrolled blood sugar
sticks out.
Assuming the number of reported adverse
reactions to the two brain drugs accurately
reflects their occurrence -- and researchers
suspect many more cases weren't reported -- the
researchers estimate the rate of hyperglycemia
among young clozapine users is 10 times greater
than among the general population. However, the
rate for those taking olanzapine doesn't seem to
be elevated, they conclude.
"The million-dollar question is whether
the cases in the MedWatch database are the tip
of the iceberg or not. We don't have a good
sense for what percent of serious adverse events
that occur in practice with marketed drugs are
ever reported to the FDA," co-author P.
Murali Doraiswamy, a Duke University
psychiatrist, says in a statement.
"The connection between pancreatitis and
these drugs is not fully known, but given its
background rate is so rare, I suspect it's a
drug toxicity," Doraiswamy says in an
e-mail interview.
Tawny Bettinger, a brain drug expert at the
University of Texas Southwestern Medical Center
who has studied the effects of antipsychotics on
blood sugar, says the problem is gaining
attention among mental health experts. "They
don't know the causes of it, or why it's
happening," says Bettinger, who cites a
number of case studies, including one she
published, that have appeared in the last
several years.
In her own work, Bettinger and her colleagues
saw that a diabetic woman taking olanzapine
quickly developed runaway blood sugar that
previously had been under control with a careful
diet. Once the woman started on the drug, even
insulin and other sugar-quelling medications
couldn't keep her glucose in check.
Fortunately, Bettinger says psychotic
patients who suffer blood sugar disruptions on
one medication can take a variety of other drugs.
Meanwhile, The Duke and FDA researchers write,
"Atypical antipsychotic agents continue to
have a role in treating pediatric psychotic
disorders, although they are not currently
labeled for pediatric use. Until systematic
studies of the various agents are conducted to
determine relative and absolute risk, physicians
should consider monitoring patients for
hyperglycemia."
Koller declined to discuss her study, and
officials at the FDA could not be reached for
comment on the findings.
Clozapine's better understood side effect is
a potentially grave falloff in white blood cells,
a problem called agranulocytosis that the FDA
has recognized for some time. Patients starting
on clozapine must undergo regular blood tests to
watch for the condition.
Last July the drug was linked to dozens of
cases of heart complications, including at least
28 deaths since the late 1980s. Novartis, which
makes a brand-name version of the pill, has
contested those figures. Even so, many mental
health experts consider the compound a miracle
drug for patients with otherwise untreatable
psychosis.
In the United States, warning labels on
atypical antipsychotics list the possibility of
sugar problems in patients who use them, but
they aren't "highlighted in any special way,"
Doraiswamy says. "In Japan, they have a
much stronger warning that is highlighted and
appears at the very first beginning of the label."
However, Doraiswamy says, "It's difficult
to further change the label in the United States
without having a sense for whether this is a
unique problem with one or two drugs or applies
to the entire class."
What To Do
A recent report on mental illness from the
U.S. Surgeon General says roughly 2.2 million
Americans have schizophrenia, split evenly
between men and women.
For more on the condition, try NARSAD, the
National Alliance for Research on Schizophrenia
and Depression or the National Institute of
Mental Health.
To learn more about atypical antipsychotics,
try About.com.
For more on hyperglycemia, check
EndocrineWeb.com or the University of
Pennsylvania.
SOURCES: Interviews with Tawny Bettinger,
Pharm.D., assistant professor of psychiatry,
University of Texas Southwestern Medical Center,
Dallas; P. Murali Doraiswamy, M.D., (via e-mail),
associate professor of psychiatry, Duke
University, Durham, N.C.; Journal of Clinical
Psychiatry; Nov. 28, 2001, Journal of the
American Medical Association~DIAB~~DRUG~~SCHZ~
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