After reviewing 199 placebo-controlled trials of antiepileptic drugs (AEDs) in 2008, the US Food and Drug Administration (FDA) issued a warning that usage of the drugs could result in heightened risk of suicidality. They also added a public health advisory requiring that “health care professionals should notify patients and caregivers of the potential for an increase in the risk of suicidal thoughts or behaviors so that patients may be closely observed.” The meta-analysis found that the absolute risk of suicidal thinking or behaviour was 0.43% in those taking AEDs versus 0.24% in the group on placebo. That equates to one additional case of suicidal thoughts or behaviour for every 500 patients taking an AED.
The limitations of randomised trials in evaluating uncommon adverse effects are well known. Short duration of follow-up and lack of accurate data on outcomes are reasons why large observational studies offer an important alternative perspective. In this case control study, Arana and colleagues make use of a UK database of primary care attenders to provide an analysis of risk by indication for prescription. They found that AEDs were not associated with an increased risk of attempted or completed suicide among patients with epilepsy (OR 0.59, 95% CI 0.35 to 0.98) or bipolar disorder (1.13, 95% CI 0.35 to 3.61). However, there was an increased risk in depressed patients (OR 1.65, 95% CI 1.24 to 2.10) and notably in those without epilepsy, depression or bipolar disorder (2.57, 95% CI 1.78 to 3.71). A plausible explanation for this latter finding is that AEDs may have been prescribed for chronic pain, which itself is associated with an increased risk of suicide.
This study indicates that the underlying illness provides a greater risk of suicidal behaviour than the prescription of AEDs. Advisory warnings may promote monitoring for suicidal thoughts, but this must be set against the risk of people with epilepsy declining or stopping treatment, as was the case with the FDA warnings on antidepressants.1 Unlike depression, there are no ready alternative treatments for epilepsy.