Pharmacological treatment and SUDEP risk: A nationwide population-based case-control study

ObjectiveWe conducted a nationwide case-control study in Sweden to test the hypothesis that antiepileptic drugs (AEDs), mono- polytherapy, adherence, antidepressants, neuroleptics, beta-blockers, and statins are associated with sudden unexpected death in epilepsy (SUDEP) risk.MethodsIncluded were 255 SUDEP cases and 1148 matched controls. Information on clinical factors and medications came from medical records and the National Patient and Prescription Registers. The association between SUDEP and medications was assessed by odds ratios (OR) with 95% confidence intervals (CI) adjusted for potential risk factors including type of epilepsy, living conditions, co-morbidity and frequency of generalized tonic-clonic seizures (GTCS).ResultsPolytherapy, especially taking three or more AEDs was associated with a substantially reduced risk of SUDEP (OR 0.31, 95% CI0.14-0.67). Combinations including lamotrigine (OR 0.55, 95% CI 0.31-0.97), valproic acid (OR 0.53, 95% CI0.29-0.98) and levetiracetam (OR 0.49, 95% CI 0.27-0.90) were associated with reduced risk. No specific AED was associated with increased risk. Regarding monotherapy, although limited numbers, the lowest SUDEP risk was seen in users of levetiracetam (0.10, 95% CI0.02-0.61). Having non-adherence mentioned in the medical record was associated with an OR of 2.75 (95% CI 1.58-4.78). Statin use was associated with a reduced SUDEP risk (OR 0.34, 95% CI0.11-0.99) but not SSRI use.InterpretationThese results provide support for the importance of medication adherence and intensified AED treatment for patients with poorly controlled GTCS in the efforts to reduce SUDEP risks and suggest that comedication with statins may reduce risks.