Neurological complication may result from rapid withdrawal from pregabalin

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News-Medical.Net Wednesday, 6-Jul-2005

Neurological complication may result from rapid withdrawal from

pregabalin

A report in the July ls 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. "

http://www.mgh.harvard.edu/