Study says Tourette drug did not cause death

BY EASHA ANAND
Staff Reporter

The death of a test subject in a Yale study was deemed unlikely to
be related to a trial drug for Tourette Syndrome, according to a
study due to be published this June.

The subject, a 34-year-old Tourette sufferer who died five years ago
from a heart attack, was one of 10 Tourette patients treated with
the antipsychotic ziprasidone, according to the paper.

Following audits by the Food and Drug Administration and Pfizer,
Inc., the makers of ziprasidone, the Yale School of Medicine's Child
Study Center group consisting of Lawrence Scahill NUR '89 EPH '97,
Jennifer Blair '97 MED '04, James Leckman and Andres Martin EPH '02
submitted the case report in early 2004.

"We did a bunch of things to reassure ourselves that we were putting
this together in the right way," Scahill said. "Unless we told the
story, the assumption might be that he passed away because of the
drug. We wanted to be transparent."

Deaths caused by drugs in clinical trials are very rare, Yale School
of Medicine Dean Robert Alpern said, because researchers
experimenting on humans have done everything possible to ensure the
drug's safety.

"Researchers bend over backwards to not put a patient at risk," he
said. "A lot of studies are done on animals before [researchers]
even go near a patient."

Ziprasidone, manufactured under the name of Geodon, was not
initially approved by the FDA because of fears of cardiac
complications, specifically disruption of the electrical signals
regulating heartbeat, Scahill said. But the coroner's report
attributed death to blockages of three of the individual's arteries.

Deanna Kelly, a professor at the Maryland Psychiatric Research
Center, said ziprasidone, like hundreds of other drugs, prolongs the
duration of electrical activity, known as the QT interval, that
causes the heart to contract. Though such prolongation could
hypothetically lead to Torsades de Pointes syndrome, a sometimes
fatal irregular heartbeat, extensive safety trials indicate the
danger is minimal, she said.

"There is a black box warning not to use this drug in combination
with other drugs lengthening the QT interval … but that is just a
cautionary measure," she said. "There have been no cases of this
arrhythmia occurring."

Ziprasidone is approved for treatment of schizophrenia in adults,
and Scahill's group was investigating its use in treating children.
The patient who died was the only adult involved in the study, which
included 24 individuals with Tourette Syndrome, autism or obsessive-
compulsive disorder.

"He had a very bad case of Tourette Syndrome and had been through
all the usual medications, which were only partially beneficial,"
Scahill said. "We helped wean him off the medications he was on, and
the ironic part is that he actually did much better on this drug."

Tourette Syndrome, a neurological disease characterized by sudden,
involuntary and repeated movements or vocalizations known as tics,
affects as many as one in 200 people.

The deceased patient had several risk factors for cardiac
complications, including a family history of cardiac arrest and a
smoking habit, according to the study. Scahill said though the
patient gained weight during the trial period, regular monitoring of
the patient indicated no abnormalities in his heart rate or
increases in fat or cholesterol in the bloodstream.

Ziprasidone is one of the newer, so-called atypical antipsychotics,
which are not associated with the extreme side effects of older
schizophrenia treatments. The drug is popular because it is not
linked to the cholesterol increases and cardiovascular risks of
other drugs, Kelly said, and some studies indicate ziprasidone may
improve a patient's cardiac health.

The School of Medicine is one of a number of research units funded
by the National Institute of Mental Health to develop guidelines for
the use of FDA-approved drugs in children.

"Historically, drug companies have been reluctant to do studies on
kids for a lot of reasons, not the least of which is the standard
criticism of, 'Why are you giving drugs to kids?'" Scahill said.

When the study began, ziprasidone had not been approved by the FDA,
and the Yale group made a special request to both Pfizer and the FDA
to allow it to experiment with the drug.

The Child Study Center is currently testing two other antipsychotic
drugs, risperidone and citalopram, on the same populations, Scahill
said.

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Source:
http://www.yaledailynews.com/article.asp?AID=28955

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Tourette-Updates
Paul Marshall
editor@...