Withdrawal/cerebral endema with off-label drugs...

[Guest guest]

http://www.nytimes.com/2005/07/19/health/policy/19drug.html

Case Raises New Concern Over Withdrawal of Drugs

By NICHOLAS BAKALAR

Published: July 19, 2005

In recent years, many anticonvulsant drugs have been widely prescribed not only

for seizure disorders, but for various kinds of chronic pain and for several

different psychiatric illnesses, even though few have been approved by the Food

and Drug Administration for those purposes.

Now researchers are reporting a case of brain swelling, or cerebral edema, after

abrupt withdrawal from pregabalin (Lyrica), a new antiepileptic drug that will

be available this fall. The report appears online and in the August issue of

ls of Neurology.

The patient, an 80-year-old woman, was in a clinical trial testing the drug for

the severe pain of shingles, or postherpetic neuralgia. About a day after

abruptly discontinuing it, she suffered nausea, headache and loss of balance,

which progressed to delirium and hallucinations a week later. An M.R.I. scan

revealed swelling in the same part of the brain that is affected in some

epileptic patients who suddenly stop their drugs.

Dr. Anne Louise Oaklander, the lead author on the paper, acknowledged that a

single case did not constitute proof. " Maybe it's completely coincidental that

she had M.R.I. abnormalities and a neurological illness, and that she'd recently

stopped the drug, " she said. " But the more likely explanation is that these

things are linked. "

Dr. Berelowitz, a vice president of Pfizer, the manufacturer of

pregabalin, said this case illustrated that " when you stop a medication, you

should stop it under physician guidance and according to the instructions. "

" We've studied close to 9,000 patients in 53 studies, " he continued, " and it's

out of this that we develop the indications and the labeling we're seeking. "

Pregabalin has been approved for the adjunctive treatment of epilepsy, and for

the nerve pain caused by diabetes and shingles.

Not all experts agree that withdrawal from these drugs is a significant problem

that warrants a special warning. Dr. Hollander, director of clinical

psychopharmacology at Mount Sinai Hospital in New York, said that pregabalin,

although not approved for the purpose, had had good results in treating anxiety.

" I don't think you need to warn patients about withdrawal, " he said, " but only

suggest that in general for all medications, tapering is better than abruptly

stopping. "

Pregabalin is chemically close to the anticonvulsant Neurontin, also made by

Pfizer and approved for both nerve pain and epilepsy. Neurontin is widely used

for other kinds of chronic pain, as well as for bipolar illness, anxiety,

insomnia, social phobia, panic disorder, cocaine craving and alcohol withdrawal,

though not specifically approved for them.

It is legal and ethical for doctors to prescribe drugs in any way they believe

will help patients, but drug companies cannot promote products for those

symptoms.

Among the anticonvulsants used in psychiatric illnesses, only Depakote and

Lamictal are approved for psychiatric disorders. Some anticonvulsants, Tegretol

for example, are approved for chronic pain, but others, like Dilantin, are

prescribed for pain without F.D.A. approval. While it is well known that sudden

withdrawal from the drugs can cause seizures in epilepsy patients, there is

little information about withdrawal in people not suffering from seizures.

Dr. Oaklander, an assistant professor of anesthesiology and neurology at

Harvard, said that at first everyone thought her patient had the flu, until the

severe neurological symptoms set in and brain imaging confirmed a serious

problem.

" I haven't heard of any other similar cases of clinical illness caused by sudden

discontinuance of these meds, but it's possible that other cases have gone

unrecognized and now we'll start to hear about them, " she said.

People with the edema of high altitude sickness have similar symptoms and M.R.I.

abnormalities, and Dr. Oaklander believes this suggests a treatment. Steroids or

acetazolamide, a drug that reduces water retention, are highly effective in

altitude sickness. " It's wonderful when you can describe a new clinical

syndrome, and immediately offer a potential treatment to try, " she said.