WEDNESDAY, Aug. 4 (HealthDay News) -- In 2008, the U.S. Food and
Drug Administration required epilepsy medications to bear a warning
label about an increased risk of suicidal behaviors. The move came
after an agency review of 199 studies that found patients taking
the drugs showed about twice the risk of suicidal behavior.
But now a study of more than 5 million patients contradicts the
FDA's findings. It suggests that the increased risk of suicide has
more to do with the conditions for which these drugs are prescribed
than the medications themselves.
For the study, researchers in Spain and the United States
evaluated the health records of primary care patients in England.
They found that people with epilepsy who currently use an
antiepileptic drug are at no greater risk of suicide-related events
than those who aren't taking the medications.
"In our opinion, in the long term, it is not the drugs themselves that raise the risk of suicide, but the underlying disease for which these drugs are prescribed," said study author Dr. Alejandro Arana, an epidemiologist and managing partner at Risk MR Pharmacovigilance Services, in Zaragoza, Spain. "Treatment with antiepileptic drugs [AEDs] helps to control the psychiatric syndromes that are at the root of suicidal behavior in these patients."
At least one epilepsy expert said the new findings, published in
the Aug. 5 issue of the
New England Journal of Medicine, are powerful enough to prompt the FDA to consider reversing its decision.
"The warning on AEDs and suicide was never justified, and this data strongly argues for its removal," said Dr. Orrin Devinsky, director of the New York University Comprehensive Epilepsy Center.
"This study examined a much larger and more meaningful 'real-life' group of patients on antiepileptic drugs than the FDA study did," added Devinsky, who noted that a major flaw of the FDA analysis was that many of the people studied had more severe cases of the condition, and these patients are known to have a higher risk of suicide to begin with. Another benefit of Arana's study is that patients were followed for an average of six years, rather than the 24 weeks' follow-up in the FDA analysis.
These new findings come on the heels of two other
epidemiological studies that are also at odds with the FDA's
findings. Those studies, one by Harvard researchers and the other
by scientists in Germany, suggested that some antiepileptic
medications raise the risk of suicide, while others do not.
Arana and his colleagues studied a total of 5,130,795 patients
who were seen in a general practitioner's office for at least six
months between July 1988 and March 2008. First, they identified how
many patients were diagnosed with epilepsy, depression or bipolar
disorder (since antiepileptic medications are often given to
patients with one or more of these conditions). Then they looked at
how many people had received an antiepileptic medication that was
included in the FDA's agency review and was also available in the
The medications studied were carbamazepine (Carbatrol, Equetro,
Tegretol, Tegretol XR), gabapentin (Neurontin), lamotrigine
(Lamictal), levetiracetam (Keppra), oxcarbazepine (Trileptal),
pregabalin (Lyrica), tiagabine (Gabitril), topiramate (Topamax),
valproate (Depakote, Depakote ER, Depakene) and zonisamide
(Zonegran). Participants were followed for an average of six years.
During the study period, 8,212 people attempted suicide, and 464 of
these patients died as a result of their injuries.
Two subgroups of patients taking these medications were found to
have an increased risk of suicide: people diagnosed with
depression, and those who were prescribed an antiepileptic drug for
a condition other than epilepsy, depression or bipolar disorder.
Patients in the latter group were roughly two and a half times more
likely to attempt or commit suicide than those who didn't take an
The researchers weren't able to determine why patients were
taking an antiepileptic medication even though they didn't have
epilepsy, depression or bipolar disorder. However, they noted that
it may have been for chronic pain, which has been associated with
an increased risk of suicide.
One possible reason for the increased risk seen among these two
groups, the authors concluded, may be that "the use of
antiepileptic drugs in these patients is a marker of severe
depression or the presence of another condition that may be
associated with an increased risk of suicide-related events."
"Research is dialogue, and our study is just another brick in the wall of knowledge," said Arana, who noted that the study was funded by an unrestricted grant from drug maker Sepracor. "There is still the need to fine-tune the role of antiepileptic drugs in indications other than epilepsy, to study the risk in the initial period of treatment compared to the use afterwards, and to compare individual antiepileptic drugs when used to treat patients with identical types of epilepsy."
For more on epilepsy, go to
U.S. National Library of Medicine.