FDA.gov – The U.S. Food and Drug Administration today announced it will require the manufacturers of antiepileptic drugs to add to these products’ prescribing information, or labeling, a warning that their use increases risk of suicidal thoughts and behaviors (suicidality). The action includes all antiepileptic drugs including those used to treat psychiatric disorders, migraine headaches and other conditions, as well as epilepsy.

The FDA is also requiring the manufacturers to submit for each of these anti-seizure medications a Risk Evaluation and Mitigation Strategy, including a Medication Guide for patients. Medication Guides are manufacturer-developed handouts that are given to patients, their families and caregivers when a medicine is dispensed. The guides will contain FDA-approved information about the risks of suicidal thoughts and behaviors associated with the class of antiepileptic medications.

“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,” said Russell Katz, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “ Patients who are currently taking an antiepileptic medicine should not make any treatment changes without talking to their health care professional.”

The FDA today also disseminated information to the public about the risks associated with antiepileptic medications by issuing a public health advisory and an information alert to health care professionals. Health care 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 antiepileptic drugs which showed that patients receiving antiepileptic drugs had almost twice the risk of suicidal behavior or thoughts (0.43 percent) compared to patients receiving a placebo (0.24 percent). This difference was about one additional case of suicidal thoughts or behaviors for every 500 patients treated with antiepileptic drugs instead of placebo.

Four of the patients who were randomized to receive one of the antiepileptic drugs 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 antiepileptic drugs are unknown.

At a July 2008 public meeting, a committee of independent advisors agreed with the FDA’s findings that there is an increased risk of suicidality with the analyzed antiepileptic drugs, and that appropriate warnings should extend to the whole class of medications. The panel also considered whether the drugs should be labeled with a boxed warning, the FDA’s strongest warning. The advisers recommended against a boxed warning and instead recommended that a warning of a different type be added to the labeling and that a Medication Guide be developed.

The following antiepileptic drugs, some of which are also used as mood stabilizers or for other psychotropic purposes in psychiatry, 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, Pregabalin (Lyrica), Primidone (Mysoline), Tiagabine (Gabitril), Topiramate (Topamax), Trimethadione (Tridione), Zonisamide (Zonegran). Some of these anti-seizure medications are also available as generics.