FDA Warns Antiepileptic Medications May Increase Risk of Suicide

The U.S. Food and Drug Administration issued new information to health care professionals on January 31, 2008, to alert them about an increased risk of suicidal thoughts and behaviors (suicidality) in patients who take antiepileptic drugs to treat epilepsy, bipolar disorder, migraine headaches and other conditions.

The FDA analyzed 199 studies comparing 11 antiepileptic drugs to placebos and found that patients taking these drugs have about twice the risk of suicidal thoughts and behaviors (0.43 percent), compared with patients receiving placebo (0.22 percent). The analysis included 27,863 patients in drug treatment groups and 16,029 patients in placebo groups. There were four suicides among patients in the drug treatment groups and none among patients in placebo groups. There were 105 reports of suicidal thoughts or behaviors in the drug-treated patients and 35 reports in placebo-treated patients. While the risk in patients receiving the medications appeared double to those who did not receive the drug, the overall risks appear to be small.  

The FDA has monitored the drugs since 2005, following a preliminary analysis of data from several antiepileptic drugs that suggested an increased risk of suicidality.

The higher risk of suicidal thoughts and behaviors was observed at one week after starting a drug and continued to at least 24 weeks. The results were generally consistent among all the different drug products studied and were seen in all demographic subgroups. There was no clear pattern of risk across age groups.

Antiepileptic drugs in the analyses included the following:

• Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)
• Felbamate (marketed as Felbatol)
• Gabapentin (marketed as Neurontin)
• Lamotrigine (marketed as Lamictal)
• Levetiracetam (marketed as Keppra)
• Oxcarbazepine (marketed as Trileptal)
• Pregabalin (marketed as Lyrica)
• Tiagabine (marketed as Gabitril)
• Topiramate (marketed as Topamax)
• Valproate (marketed as Depakote, Depakote ER, Depakene, Depacon)
• Zonisamide (marketed as Zonegran)

Some of these drugs are also available in generic form.

Although only the drugs listed above were part of the analysis, the FDA expects that all medications in the antiepileptic class share the increased risk of suicidality.

The FDA will discuss these data with a panel of experts who will be able to further clarify the true risk associated with these drugs. The agency will also work with manufacturers of antiepileptic drugs to include the new information on the labeling of these products.

Please note: Patients who are currently taking antiepileptic medicines should not make any changes without first talking to their health care provider. Health care providers 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 for notable changes in behavior.

Source: Adapted from a press release from the Food and Drug Administration.