The FDA alert on suicidality and antiepileptic drugs: Fire or false alarm?
In January 2008, the U.S. Food and Drug Administration (FDA) issued an alert about an increased risk for suicidality in 199 clinical trials of 11 antiepileptic drugs (AEDs) for three different indications, including epilepsy. An advisory panel voted against a black-box warning on AED labels, and the FDA has accepted this recommendation. We discuss three potential problems with the alert. First, adverse event data were used rather than systematically collected data. Second, the 11 drugs grouped together as a single class of AEDs have different mechanisms of action and very different relative risks, many of which were not statistically significant and some of which were smaller than one. These facts suggest that they should not be grouped as a class. Third, the risk of adverse effects from uncontrolled seizures almost certainly outweighs the small risk of suicidality. We place our comments in the context of a review of the literature on suicidality and depression in epilepsy and the sparse literature on AEDs and suicidality. We recommend that all patients with epilepsy be routinely evaluated for depression, anxiety, and suicidality, and that future clinical trials include validated instruments to systematically assess these conditions to determine whether the possible signal observed by the FDA is real.
Hesdorffer
Dale C
DC
Gertrude H. Sergievsky Center and Department of Epidemiology, Columbia University, New York, NY 10032, USA. dch5@columbia.edu
Kanner
Andres M
AM
D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use*; D004827:Epilepsy / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D013405:Suicide / Q000706:statistics & numerical data*; D014481:United States; D014486:United States Food and Drug Administration
D000927:Anticonvulsants