FDA: Antiepileptics Linked to Increased Risk of Suicidal Thoughts, Behaviour

ROCKVILLE, Maryland --
The US Food and Drug Administration has announced today that it will require the manufacturers of anti epileptic drugs to add to these products' prescribing information, or labeling, a warning that their use increases risk of suicidal thoughts and behaviors. The action includes all anti epileptic drugs including those used to treat psychiatric disorders, migraine headaches, and other conditions, as well as epilepsy.

The FDA is also requiring that the manufacturers submit for each of these products a Risk Evaluation and Mitigation Strategy, including a Medication Guide for patients. The guides will contain FDA-approved information about the risks of suicidal thoughts and behaviors associated with the class of anti epileptic medications.

"Patients being treated with anti epileptic 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," said Russell Katz, MD, Division of Neurology Products, FDA's Center for Drug Evaluation and Research, Rockville, Maryland. "Patients who are currently taking an anti epileptic medicine should not make any treatment changes without talking to their health care professional."

Healthcare professionals should notify patients, their families, and caregivers of the potential for an increase in the risk of suicidal thoughts or behaviors so that patients may be closely observed.

The FDA's actions are based on the agency's review of 199 clinical trials of 11 anti epileptic drugs which showed that patients receiving anti epileptic drugs had almost twice the risk of suicidal behavior or thoughts (0.43%) compared with patients receiving a placebo (0.24%). This difference was about 1 additional case of suicidal thoughts or behaviors for every 500 patients treated with anti epileptic drugs instead of placebo.

Of the patients who were randomized to receive one of the anti epileptic drugs, 4 committed suicide, whereas none of the patients in the placebo group did.
Results were insufficient for any conclusion to be drawn about the drugs' effects on completed suicides.
The biological reasons for the increase in the risk for suicidal thoughts and behavior observed in patients being treated with anti epileptic drugs are unknown.

Acting under the authorities of the Food and Drug Administration Amendments Act of 2007 (FDAAA), the FDA is requiring manufacturers of anti epileptic drugs to submit to the agency new labeling within 30 days, or provide a reason why they do not believe such labeling changes are necessary. In cases of non-compliance, FDAAA provides strict time lines for resolving the issue and allows the agency to initiate an enforcement action if necessary.

The following anti epileptic drugs are required to add warnings about the risk of suicidality:

carbamazepine (Carbatrol, Equetro, Tegretol, Tegretol XR); clonazepam (Klonopin); 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); phenytoin (Dilantin Suspension); pregabalin (Lyrica); primidone (Mysoline); tiagabine (Gabitril); topiramate (Topamax); trimethadione (Tridione); and zonisamide (Zonegran).
Some of these medications are also available as generics.

Health care professionals and consumers may report serious adverse events or product quality problems with the use of these products to the FDA's MedWatch Adverse Event Reporting program either online, by regular mail, fax or phone.

-- Online : www.fda.gov/MedWatch/report.htm

-- Regular Mail : use postage-paid FDA form 3500 available at: www.fda.gov/MedWatch/getforms.htm and mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787
-- Fax: (800) FDA-0178
-- Phone: (800) FDA-1088


SOURCE: US Food and Drug Administration