Antiseizure medication and SUDEP - a need for unifying methodology in research

The risk of sudden unexpected death in epilepsy (SUDEP) increases with the frequency of generalized tonic-clonic seizures. Carbamazepine (CBZ) and lamotrigine (LTG) have been suggested to increase the risk. However, the prevailing viewpoint is that the choice of antiseizure medication (ASM) does not influence the occurrence. We have explored the approach to addressing this question in relevant studies to evaluate the validity of the conclusions reached. A systematic search was performed in PubMed to identify all controlled studies on SUDEP risk in individuals on CBZ or LTG. Studies were categorized according to whether idiopathic generalized epilepsy (IGE) or females were considered separately, and whether data were adjusted for seizure frequency. Eight studies on CBZ and six studies on LTG were identified. For CBZ, one study showed a significantly increased risk of SUDEP without adjustment for seizure frequency. Another study found significantly increased risk after statistical adjustment for seizure frequency and one study found increased risk with high blood levels. Five other studies found no increase in risk. For LTG, one study showed a significantly increased risk in patients with IGE as opposed to focal epilepsy, and another study showed a significantly increased risk in females. None of the subsequent studies on LTG and none of the studies on CBZ considered females with IGE separately. Taken together the available studies suggest that LTG, and possibly CBZ, may increase occurrence of SUDEP when used in females with IGE. Additional studies with sub-group analysis of females with IGE are needed.