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Variability of antiepileptic medication taking behaviour in sudden unexplained death in epilepsy: hair analysis at autopsy

¹ Department of Pharmacology, Therapeutics and Toxicology, Cardiff University, University Hospital of Wales, Heath Park, Cardiff, CF14 4XW, UK
² The Welsh Epilepsy Unit, Cardiff University, University Hospital of Wales, Heath Park, Cardiff, CF14 4XW, UK
³ Department of Medical Statistics, Cardiff University, University Hospital of Wales, Heath Park, Cardiff, CF14 4XW, UK
⁴ Department of Neuropathology, Lancashire Teaching Hospitals NHS Trust, Fulwood, Preston, PR3 9HT, UK
⁵ Department of Psychological Medicine, Cardiff University, University Hospital of Wales, Heath Park, Cardiff, CF14 4XW, UK

Correspondence to:
Correspondence to:
Dr P E M Smith
The Epilepsy Unit, University Hospital of Wales, Cardiff, CF14 4XW, UK; SmithPE{at}cardiff.ac.uk

Background: Variable compliance with antiepileptic drugs (AEDs) is a potentially preventable cause of sudden unexplained death in epilepsy (SUDEP). Hair AED concentrations provide a retrospective insight into AED intake variability.

Methods: We compared hair AED concentration variability in patients with SUDEP (n = 16), non-SUDEP epilepsy related deaths (n = 9), epilepsy outpatients (n = 31), and epilepsy inpatients (n = 38). AED concentrations were measured in 1 cm hair segments using high performance liquid chromatography. Individual patient hair AED concentration profiles were corrected for "washout" using linear regression analysis. The coefficient of variation (CV) of the corrected mean hair AED concentration provided an index of variability of an individual’s AED taking behaviour. Hair sample numbers varied between subjects, and so weighted regression estimates of the CV were derived for each group.

Results: The CV regression estimates for each group were: SUDEP 20.5% (standard error 1.9), non-SUDEP 15.0% (3.9), outpatients 9.6% (1.4), and inpatients 6.2% (2.7). The SUDEP group therefore showed greater hair AED concentration variability than either the outpatient or the inpatient groups (p<0.0001).

Conclusion: Observed variability of hair AED concentrations, reflecting variable AED ingestion over time, is greater in patients dying from SUDEP than in either epilepsy outpatients or inpatients. SUDEP, at least in a proportion of cases, appears preventable.

Abbreviations: AED, antiepileptic drug; CV, coefficient of variation; SD, standard deviation; SUDEP, sudden unexplained death in epilepsy

Keywords: antiepileptic drugs; compliance; epilepsy; hair; SUDEP

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