FDA Warns of Risk of Suicidal Thoughts and Behavior with Antiepileptic Drugs

Elizabeth Stump

The Food and Drug Administration (FDA) reported a 0.43 percent increased risk of
suicidal behavior or ideation in patients receiving antiepileptic drugs compared to a 0.22
percent increase among those on placebo. The FDA is urging physicians to closely
monitor patients for behavioral changes and for patients to be aware of this serious side
effect, and the agency is also working with the manufacturers of the antiepileptic drugs to
add this new information to the labels.

The FDA analyzed 199 suicidality reports from placebo-controlled clinical studies
of 11 antiepileptic drugs used to treat epilepsy, bipolar disorder, migraine headaches, and
other conditions. The higher risk of suicidality among those on antiepileptics was seen
after the first week of starting the drug and continued to at least 24 weeks. Patients with
epilepsy had a higher relative risk for suicidality compared to patients with a different
psychiatric condition.

The drugs analyzed include (some of these are also available in generic form):
carbamazepine (Carbatrol, Equetro, Tegretol, Tegretol XR); felbamate (Felbatol);
gabapentin (Neurontin); lamotrigine (Lamictal); levetiracetam (Keppra); oxcarbazepine
(Trileptal); pregabalin (Lyrica); tiagabine (Gabitril); topiramate (Topamax); valproate
(Depakote, Depakote ER, Depakene, Depacon); and zonisamide (Zonegran).

Although the FDA analysis included only the drugs listed above, the agency
expects that all antiepileptic drugs share the increased risk of suicidality and that labeling
changes will be applied broadly to the entire drug class. The FDA is not advising
physicians to stop prescribing these products because it has not established a causal
relationship between antiepileptics and suicide risk.

Alan B. Ettinger, MD, professor of clinical neurology at Albert Einstein College

of Medicine and director of the North Shore-LIJ Comprehensive Epilepsy Centers in
New Hyde Park, NY, said that it is difficult to identify specific causes for depression and
suicidal ideation and many factors should be considered.

“The relationship of depression and suicide with epilepsy is a complex one and
relate in part to commonalities in the underlying central nervous disorders that can rise to
both problems as well as many other factors such as medication effects,” he said. “It is
intuitive that medications that affect the CNS in controlling seizures also have positive
and negative psychotropic effects. This means that in the selection and the follow-up of
patients receiving antiepileptic drugs, the clinician needs to place more emphasis on
querying for evidence of alteration in mood.”

For more information, visit:

www.fda.gov/cder/drug/InfoSheets/HCP/antiepilepticsHCP.htm.