Among people with epilepsy, there is a 20-fold higher risk of dying suddenly and 
unexpectedly compared with the general population. This phenomenon is called 
sudden unexpected death in epilepsy (SUDEP) and the term is used when sudden 
death occurs in an otherwise reasonably healthy person with epilepsy and the 
autopsy is unrevealing. In most cases, SUDEP occurs during sleep and is 
unwitnessed. Risk factors for SUDEP include the presence or number of 
generalized tonic-clonic seizures (GTCS), nocturnal seizures, young age at 
epilepsy onset, longer duration of epilepsy, dementia, absence of 
cerebrovascular disease, asthma, male gender, symptomatic aetiology of epilepsy 
and alcohol abuse. Suggested factors predisposing to SUDEP have included 
long-QT-related mutations, impaired serotonergic brain stem control of 
respiration, altered autonomic control and seizures with a pronounced postictal 
suppression and respiratory compromise. Final events that may lead up to SUDEP 
are a postictal CNS shutdown with pronounced EEG suppression, ictal or postictal 
apnoea, and ictal cardiac arrhythmia. It is unknown whether antiepileptic drugs 
(AEDs) modify the risk for SUDEP. Studies have consistently found that the 
presence or number of GTCS is associated with an increased risk for SUDEP. Since 
continued presence of GTCS clearly necessitates the use of AEDs, both factors 
must be taken into account to determine whether one or both increases the risk 
for SUDEP. Some studies suggest that AEDs, such as lamotrigine and 
carbamazepine, may increase the risk of SUDEP, but rarely adjust for GTCS. Other 
studies, which have found that AEDs are associated with a decreased SUDEP risk, 
either adjust for the number of GTCS or are meta-analyses of randomized clinical 
trials. Studies assessing the impact of AEDs on the risk for SUDEP are limited 
because SUDEP is a rare event, making randomized clinical trials impossible to 
conduct. Observational studies focus on whether or not an AED was prescribed. 
When postmortem AED concentrations are assessed they are usually low or absent, 
perhaps due to sampling in deceased individuals, making it difficult to fully 
resolve whether AEDs increase or decrease SUDEP risk. Despite these caveats, the 
evidence suggests that AEDs are not associated with an increased risk for SUDEP 
on a population level, although some individuals may be susceptible to effects 
of AEDs. Recent evidence from a meta-analysis of randomized clinical trials of 
adjunctive AEDs at efficacious doses provides strong support for AED treatment 
as mono- or polytherapy to increase seizure control and protect against SUDEP in 
patients with refractory epilepsy. For patients for whom seizure control is 
unattainable, supervision or monitoring may prevent SUDEP, though this has never 
been formally tested.