To the Editors:
In a recent article published in Epilepsia (Hesdorffer et al., 2012), the authors state that they have provided a consistent message that the number of generalized tonic–clonic seizures (GTCS) and not antiepileptic drugs (AEDs) increases the risk of sudden unexpected death in epilepsy (SUDEP). The authors make no reservations concerning possible subgroups of patients with epilepsy to which this conclusion may not apply.
In our opinion there is no scientific disagreement that the number of GTCS is likely the most important risk factor for SUDEP. However, we question whether the authors by using the methods described (Hesdorffer et al., 2012) have scientifically proven that the use of lamotrigine (LTG) in female patients with idiopathic generalized epilepsy (IGE) does not imply an increased risk of SUDEP.
By combining data from England and Scotland, the same authors, in a previous publication (Hesdorffer et al., 2011), documented in a univariate analysis a significantly increased risk of SUDEP in patients with IGE who were treated with LTG. In the last study, they combined data from England and the United States, and after controlling for the frequency of primary or secondary GTCS, LTG was no longer associated with a significantly increased risk of SUDEP. It is surprising that the same authors who previously analyzed the subgroup with IGE separately and found an increased risk with LTG in their last report conclude that there is no association between AEDs and SUDEP without having analyzed the IGE subgroup separately.
We have recently reported an increased risk of SUDEP in female patients using LTG and argued that our findings may be due to an interaction between genes and the AED in patients with idiopathic epilepsy (Aurlien et al., 2012). Of interest, Hesdorffer et al. (2012), by combining localization-related epilepsy and IGE, found an OR for SUDEP with LTG monotherapy of 0.4 in male and 6.6 in female patients. In our opinion, although this difference is not statistically significant, this does not prove that the difference is clinically unimportant. At least, the same analysis should be conducted for the subgroup of female patients with IGE before a firm conclusion of a lack of association between LTG and SUDEP may be scientifically valid.