Antipsychotic Drugs Tied to Blood Sugar Trouble
By Adam Marcus HealthScoutNews Reporter November 28, 2001

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 (news - web sites) (FDA), appear as a letter in the Nov.
28 issue of the Journal of the American Medical Association (news - web
sites).

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."

Source:
http://dailynews.yahoo.com/h/hsn/20011127/hl/antipsychotic_drugs_tied_to_blood