Sudden unexpected death in epilepsy (SUDEP) accounts for approximately 2% of 
deaths in population-based cohorts of epilepsy, and up to 25% of deaths in 
cohorts of more severe epilepsy. When it occurs, SUDEP usually follows a 
generalised tonic-clonic seizure. Unresponsiveness, apnoea, and cardiac arrest 
occur in SUDEP, rather than the typical gradual recovery. The great majority of 
tonic-clonic seizures occur without difficulty and how the rare seizure 
associated with SUDEP differs from others is unknown.Three mechanisms have been 
proposed for SUDEP: cardiac arrhythmia, neurogenic pulmonary oedema, and 
postictal suppression of brainstem respiratory centres leading to central 
apnoea. Recent studies have found that the incidence of SUDEP increases with the 
severity of epilepsy in the population studied. The duration of epilepsy, number 
of tonic-clonic seizures, mental retardation, and simultaneous treatment with 
more than two antiepileptic drugs are independent risk factors for SUDEP. Some 
studies have reported that carbamazepine use, carbamazepine toxicity, and 
frequent, rapid changes in carbamazepine levels, may be associated with SUDEP. 
Other evidence indicates that carbamazepine could potentially increase the risk 
for SUDEP by causing arrhythmia or by altering cardiac autonomic function. 
However, this evidence is tenuous and most studies have not found an association 
between the use of carbamazepine or any other individual antiepileptic drug and 
SUDEP. There is little information regarding antiepileptic drugs other than 
phenytoin and carbamazepine. The incidence of SUDEP with gabapentin, tiagabine, 
and lamotrigine clinical development programmes is in the range found in other 
populations with refractory epilepsy. This suggests that these individual 
antiepileptic drugs are no more likely to cause SUDEP than antiepileptic drugs 
in general. Best current evidence indicates that the risk of SUDEP can be 
decreased by aggressive treatment of tonic-clonic seizures with as few 
antiepileptic drugs as necessary to achieve complete control. At present there 
is no strong reason to avoid any particular antiepileptic drug. Further studies 
are needed to elucidate the potential role of individual antiepileptic drugs in 
SUDEP and establish clinical relevance, if any. These studies may be challenging 
to conduct and interpret because SUDEP is relatively uncommon and large numbers 
will be necessary to narrow confidence intervals to determine the clinical 
relevance. Also adjustments will be needed to account for the potent risks 
associated with other independent factors.