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.