FDA Adds Suicide Warning to drugs

[Guest guest]

FDA Adds Suicide Warning to Epilepsy Drugs

By Steve Reinberg HealthDay Reporter

Tuesday, December 16, 2008; 12:00 AM

TUESDAY, Dec. 16 (HealthDay News) -- The U.S. Food and Drug

Administration announced Tuesday that it was adding a label warning on

heightened suicide risk for users of antiepileptic drugs.

The move, which follows the advice last summer of an FDA advisory

panel, stops short of slapping the strongest " black box " warning on

this class of drugs, which includes widely used medications such as

clonazepam (Klonopin), phenytoin (Dilantin) and topiramate (Topamax).

" Patients being treated with antiepileptic drugs for any indication

should be monitored for the emergence or worsening of depression,

suicidal thoughts or behavior, or any unusual changes in mood or

behavior, " Dr. Katz, director of the division of neurology

products in the FDA's Center for Drug Evaluation and Research, said in

an agency news release.

But, he added, " patients who are currently taking an antiepileptic

medicine should not make any treatment changes without talking to

their health care professional. "

The warning includes a heightened risk to users of " suicidal thoughts

and behaviors (suicidality), " the agency announcement said.

The FDA is also requiring that manufacturers draw up Medication Guides

handouts that outline the risks and can be given to patients and their

families when the medications in question are prescribed.

Tuesday's move follows recommendations in July from a 20-member

advisory panel that voted unanimously, with one abstention, to back

the scientific findings on 11 antiepileptic drugs studied by the agency.

In late January of 2008, the FDA announced it was considering a black

box warning after an agency review of 199 studies comparing the drugs,

which are used by millions, to placebos. That review found that

patients taking the drugs had about twice the risk of suicidal

behavior compared with patients taking a placebo.

The absolute risk amounted to about 1 added case of suicidal thoughts

or behaviors for every 500 patients taking the antiepileptic drugs

versus placebo. The mechanism linking antiepileptic drugs with

potetial suicide risk remains unknown, the FDA said.

" We have concluded this was a real signal, and the signal applied to

all drugs we studied, " Dr. Katz, director of the division of

neurology products at the FDA's Center for Drug Evaluation and

Research, told reporters in July.

" We propose that labels for all these antiepileptic drugs be changed

to include a box warning, and patients should be given a medication

guide describing these events with each prescription refill, " he said.

The advisory panel appeared to agree with him -- up to a point. It

voted in favor of sending a medication guide to doctors detailing the

suicide risks, but not the boxed warning. A majority of panel members

voted against adding the black box warning, saying the studies didn't

show a high enough risk for suicidal behavior.

" The general view of the committee was concern that patients or

physicians would not prescribe these drugs in certain circumstances

where they should, " Katz said.

One specialist said Tuesday that he remained skeptical of any strong

link between antiepileptics and suicide.

Dr. Gholam Motamedi, director of clinical neurophysiology fellowship

and epilepsy at town University Hospital in Washington, D.C.,

said it was " surprising to attribute suicide to the antiepileptic

drugs per se, because a good number of these drugs are used in

psychiatry for their positive effects on mood and depression.

Nevertheless, this emphasizes the importance of screening for signs

and symptoms of depression and suicidal tendencies in the epilepsy

clinics. "

He also pointed to studies that have shown that people with epilepsy

tend to have a higher incidence of depression, which is tied to suicide.

" Therefore, this increased rate of suicide may tell us patients with

epilepsy may have higher rate of suicide, but it doesn't mean it's

'caused' by the anti-seizure drugs, " Motamedi said.

" The better warning would be, in my opinion, to be sensitive to

depression of other psychiatric symptoms in epilepsy patients and

refer them to psychiatrists, " he added.

In addition to clonazepam, phenytoin and topiramate, the drugs covered

by the new FDA-mandated labeling are: carbamazepine (marketed as

Carbatrol, Equetro, Tegretol, Tegretol XR);clorazepate (Tranxene);

divalproex sodium (Depakote, Depakote ER, Depakene); ethosuximide

(Zarontin);ethotoin (Peganone); felbamate (Felbatol); gabapentin

(Neurontin);lamotrigine (Lamictal); lacosamide (Vimpat); levetiracetam

(Keppra);mephenytoin (Mesantoin); methosuximide (Celontin);

oxcarbazepine (Trileptal);pregabalin (Lyrica); primidone (Mysoline);

tiagabine (Gabitril);trimethadione (Tridione), and zonisamide

(Zonegran).Some of these drugs are also available as generics.

According to the FDA, antiepileptic drugs are used to treat epilepsy,

bipolar disorder, migraine headaches and other conditions.

More information

For more on epilepsy, visit the Epilepsy Foundation.

SOURCES: Dec. 16, 2008, news release, U.S. Food and Drug

Administration; Gholam Motamedi, M.D.,associate professor of neurology

anddirector, clinical neurophysiology fellowship and epilepsy,

town University Hospital, Washington, D.C; July 10, 2008,

teleconference with Katz, M.D., director, division of

neurology products, Centerfor Drug Evaluation and Research, FDA,

Rockville, Md.

http://www.washingtonpost.com/wp-dyn/content/article/2008/12/16/AR2008121602240.\

html