FDA warns of increased thoughts of suicide associated with antiepileptic drugs

WASHINGTON The Food and Drug Administration has released information stating that there is an increased risk of suicidal thoughts in patients taking antiepileptic drugs to treat epilepsy, bipolar disorder, migraine headaches and other conditions.

In March 2005, the FDA requested data from controlled clinical trials conducted by manufacturers of marketed antiepileptic drugs following a preliminary analysis of data from several antiepileptic drugs that suggested an increased risk of suicide. The FDA reviewed data from 199 placebo-controlled studies of 11 drugs.

An analysis from the studies showed that patients taking these drugs have about twice the risk of suicidal thoughts and behaviors (0.43 percent), compared with patients receiving a placebo (0.22 percent). This risk corresponds to an estimated 2.1 per 1,000 more patients in the drug treatment groups who experienced suicidal thoughts than in the placebo groups.

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.

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.

The FDA released the names of the antiepileptic drugs in the analyses, which 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)

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 suicide.

The FDA will be working with manufacturers of antiepileptic drugs to include this new information in the labeling for these products. The agency anticipates that labeling changes will be applied broadly to the entire class of drugs. The FDA is also planning to discuss these data at an upcoming advisory committee meeting.