Dec. 16, 2008 — The FDA today announced that it will require makers of epilepsy drugs to add a warning about increased risk of suicidal thoughts and behaviors to the products’ prescribing information or labeling.
The warning — which won’t be a “black box” warning — applies to all antiepileptic medications, including those used to treat psychiatric disorders, migraines, and other conditions, as well as epilepsy.
Here is a list of the medications required to add the warning:
- Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)
- Clonazepam (marketed as Klonopin)
- Clorazepate (marketed as Tranxene)
- Divalproex sodium (marketed as Depakote, Depakote ER, Depakene)
- Ethosuximide (marketed as Zarontin)
- Ethotoin (marketed as Peganone)
- Felbamate (marketed as Felbatol)
- Gabapentin (marketed as Neurontin)
- Lamotrigine (marketed as Lamictal)
- Lacosamide (marketed as Vimpat)
- Levetiracetam (marketed as Keppra)
- Mephenytoin (marketed as Mesantoin)
- Methosuximide (marketed as Celontin)
- Oxcarbazepine (marketed as Trileptal)
- Phenytoin (marketed as Dilantin Suspension)
- Pregabalin (marketed as Lyrica)
- Primidone (marketed as Mysoline)
- Tiagabine (marketed as Gabitril)
- Topiramate (marketed as Topamax)
- Trimethadione (marketed as Tridione)
- Zonisamide (marketed as Zonegran)
Some of those drugs are also sold generically.
“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,” Russell Katz, MD, says in an FDA news release.
Katz, who directs the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, says that “patients who are currently taking an antiepileptic medicine should not make any treatment changes without talking to their health care professional.”
The FDA also issued a public health alert about the risk and asked health care professionals to notify patients, their families, and caregivers about the risk, so that patients may be closely observed. And the FDA has ordered epilepsy drugmakers to create a risk evaluation and management strategy, including a medication guide for patients, addressing the risk.
Epilepsy Drugs and the FDA
Today’s FDA actions are based on the agency’s review of 199 clinical trials of 11 epilepsy drugs. The review, which the FDA released in January, showed that patients taking those drugs had almost twice the risk of suicidal behavior or thoughts than patients taking a placebo.
That difference was about one additional case of suicidal thoughts or behaviors for every 500 patients treated with antiepileptic drugs instead of placebo.
Four patients who were randomly assigned to take one of the epilepsy drugs committed suicide. There were no suicides in the placebo group. But the results weren’t sufficient to make conclusions about drugs’ effects on completed suicides.
The biological reasons for the increased risk of suicidal thoughts and behavior observed in patients being treated with antiepileptic drugs are unknown, notes the FDA.
In July, the FDA held a public meeting of an independent committee of experts who reviewed the data. The committee agreed with the FDA about the increased risk of suicidality and recommended warning about that risk in the drugs’ labels and in medication guides, rather than requiring a “black box” warning, which is the FDA’s sternest warning.