Antiepileptic drugs and suicidality: finding ways forward

Abstract

More than 2 years after the US Food and Drug Administration (FDA) fi rst alerted health-care providers to “an increased risk of suicidal thoughts and behaviours (suicidality)” in patients taking antiepileptic drugs (AEDs), the debate is still simmering over the agency’s decision to add warnings to the entire class of medications. But the process has forced the epilepsy community to focus on the factors that contribute to psychiatric disorders in patients with epilepsy, and the need to detect and treat these devastating comorbidities. The FDA’s safety alert in January, 2008, was based on an analysis of suicidality data from 199 randomised, placebo-controlled trials of 11 AEDs. “There was tremendous consistency across the drugs”, says Russell Katz, director of the Division of Neurology Products at the FDA. “For eight out of the 11 drugs, there was what we would call a numerical increase” in the incidence of suicidality. “And the overall estimate of suicidality, when we included all 11 drugs, was statistically signifi cant.” Katz explains that “because these drugs act in so many diff erent ways pharmacologically, that argued strongly for applying the fi nding to all drugs in the class”. At a public meeting held in July, 2008, a committee of independent advisers voted against the addition of a black-box warning—the FDA’s strongest warning—to AEDs amid fears that this might discourage patients from taking their medication and that the threat of litigation might lead to a fall in the prescribing of these drugs. Rochelle Caplan, a paediatric neuropsychiatrist at the University of California, Los Angeles, USA, who was a member of the advisory panel, explains that “the risks of not taking the medication, including death, are much higher” in patients with epilepsy than the risk of suicidality that might be associated with AEDs. In December, 2008, on the advice of the panel, the FDA announced that a less stringent warning would be added to the labelling of all drugs with an antiepilepsy claim, and that the manufacturers of AEDs would develop Medication Guides to explain the risk of suicidality to patients and their families.