FDA Will Convene Advisory Committee Meeting To Consider Whether Anti-Epileptic Drugs, Or Perhaps Epilepsy Itself, Associated With Increase In Suicidal Behaviors
(Posted by Tom Lamb at DrugInjuryWatch.com)
On January 31, 2008 the FDA issued a MedWatch email alert that stated:
[T]he Agency has analyzed reports of suicidality (suicidal behavior or ideation) from placebo-controlled clinical studies of eleven drugs used to treat epilepsy as well as psychiatric disorders, and other conditions.
The 11 anti-epileptic and psychiatric drugs that had been reviewed by the FDA were:
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); and,
Zonisamide (marketed as Zonegran).
This January 31 email referred interested parties to the complete 2008 MedWatch Safety Summary, which included a link to the Healthcare Professional Sheet regarding this epilepsy drug issue.
Additional information about some of the drug companies involved and their reactions was set forth a February 1, 2008 article, "Suicidal-Thoughts Risk Is Linked To Drugs Used to Treat Epilepsy", by Jennifer Corbett Dooren of The Wall Street Journal:
The drugs include Johnson & Johnson's Topamax, GlaxoSmithKline PLC's Lamictal, Pfizer Inc.'s Lyrica, and Novartis AG's Tegretol and Trileptal. Topamax is also approved to treat migraines, and Lyrica is approved to treat certain pain conditions from diabetes, shingles and fibromyalgia.
In a statement, Pfizer said it hasn't identified any evidence an increased risk of suicide-related events in Lyrica or Neurontin based on a review of clinical studies and post-marketing reports. GlaxoSmithKline said they would work with the FDA to update Lamictal's label if needed, and Johnson & Johnson said there is already a discussion about suicide attempts in the Topamax label. Novartis didn't immediately return requests for comment.
Another February 1 news report, "F.D.A. Finds Increase in Suicide Symptoms for Patients Using Seizure Medications", by Gardiner Harris and Benedict Carey of The New York Times, provided additional details about the FDA's analysis:
The increased risks, while double in relative terms, are small. The Food and Drug Administration undertook a combined analysis of 199 clinical trials with 43,892 patients and found 4 suicides and 105 reports of suicidal symptoms among the 27,863 patients who were given the drugs compared to no suicides and 35 reports of suicidal symptoms among the 16,029 patients treated with placebos.
Taken together, the risk of suicidal thoughts and behavior was 0.43 percent for those on drug therapy and 0.22 percent for those given placebos....
The increased risks began as early as the first week of therapy and never seemed to leave, the drug agency said. The risks were higher among epileptics than among those given the drugs for psychiatric or other problems.
This last point reminded us about an email summary "Epilepsy Doubles Suicide Risk", that was published in Physician's First Watch back on July 3, 2007; it reported that a large case-control study published early online in The Lancet Neurology had found epilepsy, itself, doubled the risk for suicide. The study cited was "Epilepsy and risk of suicide: a population-based case–control study" (Jakob Christensen, Mogens Vestergaard, Preben Bo Mortensen, Per Sidenius, Esben Agerbo, The Lancet Neurology - Vol. 6, Issue 8, August 2007, Pages 693-698). From the Physician's First Watch summary of this medical journal article:
Danish researchers identified some 450,000 people with data in five national health and socioeconomic registries. Even after differences in psychiatric history and socioeconomic status were taken into account, the risk for suicide among patients with epilepsy was twice that of people without epilepsy.
Overall, suicide risk was highest among those with both epilepsy and a history of psychiatric disease, particularly affective disorders. In addition, suicide risk was highest in the first 6 months after epilepsy diagnosis and decreased with increasing age, both among those with and those without psychiatric comorbidities.
Returning to the January 31 MedWatch alert about these 11 anti-epileptic and psychiatric drugs, the FDA said it plans to continue its review of the suicide issues at an upcoming advisory committee meeting. We look forward to hearing the ongoing discussion about this emerging drug-safety issue.