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Report describes potential problem
with new drug for seizures, pain
Neurological complication may result
from rapid withdrawal from pregabalin, more studies needed
BOSTON - July 6, 2005 - A report in the July Annals of
Neurology describes a serious adverse event experienced by a
participant in a clinical trial that may raise a new caution about
the use of antiepileptic drugs for conditions other than epilepsy.
An elderly women enrolled in a clinical trial of pregabalin, a new
drug for the treatment of pain and seizures, abruptly discontinued
the medication and then developed neurological symptoms including
headache, confusion and hallucinations. The study's authors from
Massachusetts General Hospital (MGH) suggest that all patients stopping
antiepileptic drugs (AEDs) should do so gradually to avoid complications
of withdrawal.
"The first description of complications associated with a new
drug - the 'index case' - lets doctors and patients know of the
potential for problems," says Anne Louise Oaklander, MD, PhD,
director of the MGH Nerve Injury Unit and the report's lead author.
"It doesn't tell us whether these problems are very rare or
common, but it lets everyone know to look out for more cases. There
are many questions that still need to be answered, but right now
our recommendations are that anyone using AEDs not stop them abruptly
until the risks and consequences are better known."
Patients with epilepsy have traditionally been cautioned against
suddenly halting drug treatment because abrupt withdrawal could
trigger the resumption of seizures. In recent years, however, AEDs
have been prescribed for many other conditions - including pain
syndromes and psychiatric disorders - and recommendations against
rapid withdrawal were not thought to apply to those patients.
In the current report, Oaklander and her coauthor Bradley Buchbinder,
MD, an MGH neuroradiologist, describe the experiences of an 80-year-old
women who took pregabalin as part of a clinical trial of the drug
for treatment of post-herpetic neuralgia, a painful syndrome that
can linger after shingles. After she had taken the drug for almost
a year, with good relief of her chronic pain, the woman suddenly
stopped taking pregabalin when the FDA temporarily halted all trials.
The next day she developed nausea, headache and dizziness - symptoms
at first attributed to the flu. A week later, however, she developed
hallucinations, distorted color perception and difficulty reading,
symptoms she found terrifying. Over subsequent weeks, the symptoms
improved, but the woman still feels that she has never fully recovered.
MR imaging studies of the patient's brain taken three weeks after
the onset of symptoms showed an area of edema - fluid buildup -
in a part of the brain called the corpus callosum. Similar lesions
have been seen in MR images of patients with epilepsy who had abruptly
discontinued use of other AEDs, but those changes had been attributed
to the seizures. "The fact that our patient had never had seizures
suggests that suddenly stopping these medications could be enough
to cause these problems," says Oaklander. "Also, in the
past these MRI changes have been considered not to cause illness.
Now that we know the kind of symptoms that they may produce, doctors
will be able to look more carefully at other patients with these
changes to see if they also became ill."
The researchers also noted that this patient's symptoms and MRI
changes were similar to those that occur in severe high-altitude
sickness. There are good treatments for high-altitude associated
edema, so the authors suggest that those therapies be considered
for any other patients who develop symptoms after suddenly stopping
AEDs.
Pregabalin is very similar to gabapentin (Neurontin), an antiepileptic
drug already in wide use for various conditions. Although it is
not yet on the market, pregabalin has now received preliminary FDA
approval to treat neuropathic pain and seizure disorders, and it
is expected to be widely prescribed.
"As far as I know, no one has prospectively studied the risk
of complications from withdrawal from any AEDs - either the older
drugs or the newer ones like pregabalin. And few physicians or patients
are aware that problems may occur in patients without seizures,"
says Oaklander, who is an assistant professor of Anaesthesia and
Neurology at Harvard Medical School. "We hope that this report
will both increase awareness and lead to further investigation."
The study was supported by grants from the National Institute of
Neurological Disorders and Stroke, the American Federation for Aging
Research, and Pfizer Inc., which will market pregabalin under the
brand name Lyrica.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of more than $450 million
and major research centers in AIDS, cardiovascular research, cancer,
cutaneous biology, medical imaging, neurodegenerative disorders,
transplantation biology and photomedicine. In 1994, MGH and Brigham
and Women's Hospital joined to form Partners HealthCare System,
an integrated health care delivery system comprising the two academic
medical centers, specialty and community hospitals, a network of
physician groups, and nonacute and home health services.
Media Contact: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
Information about Clinical Trials
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