Antiepileptic drug therapy and its management in sudden unexpected death in epilepsy: A case-control study

Purpose: Because frequent seizures constitute a major risk factor for sudde n unexpected death in epilepsy (SUDEP), the treatment with antiepileptic dr ugs (AEDs) may play a role for the occurrence of SUDEP. We used data from r outine therapeutic drug monitoring (TDM) to study the association between v arious aspects of AED treatment and the risk of SUDEP. Methods: A nested case-control study was based on a cohort consisting of 6. 880 patients registered in the Stockholm County In Ward Care Register with a diagnosis of epilepsy. Fifty-seven SUDEP cases, and 171 controls, living epilepsy patients, were selected from the cohort. Clinical data including d ata on TDM were collected through medical record review. Results. The relative risk (RR) of SUDEP was 3.7 (95% CI, 1.0-13.1) for out patients who had no TDM compared with those who had one to three TDMs durin g the 2 years of observation. RR was 9.5 (1.4-66.0) if carbamazepine (CBZ) plasma levels at the last TDM were above and not within the common target r ange (20-10 muM) High CBZ levels were associated with a higher risk in pati ents receiving polytherapy and in those with frequent dose changes. Althoug h the subgroup of patients with high CBZ levels was small (six cases of 33 with CBZ therapy), and the result should be interpreted with caution, no si milar associations were demonstrated for phenytoin plasma levels and risk o f SUDEP. No association was found between SUDEP risk and within-patient var iation in AED levels over time. Conclusions: Polytherapy. frequent dose changes, and high CBZ levels as ide ntified risk factors for SUDEP all point to the risks associated with an un stable severe epilepsy. It is unclear whether high CBZ levels per se repres ent a risk factor or just reflect other unidentified aspects of a severe ep ilepsy. Our results, however. prompt further detailed analyses of the possi ble role of AEDs in SUDEP in larger cohorts and suggest that reasonable mon itoring of the drug therapy mag; be useful to reduce risks.