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

Williams, John G.; Lawthom, Charlotte; Dunstan, Frank David John; Dawson, Timothy; Kerr, Michael Patrick; Wilson, John F.; Smith, Philip E. M.

doi:10.1136/jnnp.2005.067777

Cited by 53 publications

(18 citation statements)

References 13 publications

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“…In a recent study, post-mortem hair AED concentrations demonstrated that observed variability in AED-taking behavior was significantly greater in patients who had died from SUDEP compared with epilepsy outpatients or inpatients [59]. The most likely explanation was greater variability in AED ingestion among SUDEP patients.…”

Section: Compliancementioning

confidence: 98%

Sudden unexpected death in epilepsy

Johnston

Smith

2007

Expert Review of Neurotherapeutics

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Mortality in people with epilepsy is two- to three-times that of the general population. This can be attributed to epilepsy itself (epilepsy-related death) or to the underlying cause of the epilepsy. Sudden unexpected death in epilepsy (SUDEP) is the commonest cause of epilepsy-related death. It is a syndrome where a person with epilepsy dies suddenly and no other cause of death is found. There are frequent reports of persons dying alone in their sleep. It is assumed that death occurs following a seizure but since the deaths are often unwitnessed this is only an assumption. The most important risk factor appears to be poor seizure control. Lately, SUDEP has received much public interest, has been the subject of international forums, ethical debates and comprises part of national guidelines on epilepsy management. Despite its high profile, the evidence for specific risk factors and pathophysiology is still not established. Poor incident case reporting, inaccurate death certification and fewer post-mortem examinations have limited the value of epidemiological data on SUDEP. Here, we review the characteristics of SUDEP, its likely risk factors, mechanisms and differential diagnosis, and consider possible strategies for prevention. We also explore the discussion of SUDEP with patients and the management of relatives of SUDEP patients.

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Section: Compliancementioning

confidence: 98%

Sudden unexpected death in epilepsy

Johnston

Smith

2007

Expert Review of Neurotherapeutics

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“…53 Directly asking patients if they take their prescribed medication regularly, in a nonjudgmental and sympathetic way, might reveal that compliance is poor, even without blood testing; assaying drug levels in hair can give a longer-term record of compliance. 54 In the management of any epilepsy, and refractory epilepsies in particular, it is always worth ensuring, from a clinical perspective, that 'trivial' causes of apparent refractoriness have been excluded. For example, at specialist centers, a significant proportion (~20%) of patients who are evaluated for apparently refractory epilepsy turn out not to have epilepsy at all.…”

Section: Current Management Of Refractory Epilepsy Investigationsmentioning

confidence: 99%

Etiology and management of refractory epilepsies

Sisodiya

2007

Nat Rev Neurol

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The epilepsies are an important, common and diverse group of symptom complexes characterized by recurrent spontaneous seizures. Although many patients with epilepsy have their seizures controlled effectively by antiepileptic drugs (AEDs), about one-third of patients continue to have seizures, despite trying a range of AEDs. Such patients bear the heaviest burden of epilepsy, with increased morbidity and risk of premature mortality. Our current understanding of the refractory epilepsies--the most common of which are focal--is limited; even their definition is problematic. Standard treatments for refractory epilepsies include optimization of existing AED regimens, trials of further AEDs, and, for some patients, therapeutic resective neurosurgery. Recent basic research has explored possible underlying causes of refractory epilepsy, and two main hypotheses have emerged to account for the failure of AED treatment. According to one hypothesis, AEDs might fail because of alterations in the properties of their usual targets. Alternatively, they might fail because multidrug transporter mechanisms limit concentrations of the drugs at their targets. The refractory epilepsies can be viewed as offering remarkable insights into biological processes in the epilepsies, and their effective treatment remains an important aim; treatment would potentially bring much-needed relief to hundreds of thousands of patients across the world.

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“…These patients are exposed to a higher risk of seizures and an increased time to remission [4]. Low adherence to AEDs may also be associated with increased mortality including sudden unexplained death [5], and hospital admissions [6]. Whilst large crosssectional studies have demonstrated substantial difference in health outcomes between patients with high and low adherence, prospective studies are lacking.…”

Section: Introductionmentioning

confidence: 99%

Economic evaluation of a behavior-modifying intervention to enhance antiepileptic drug adherence

Plumpton

Brown

Reuber

et al. 2015

Epilepsy & Behavior

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Between 35% and 50% of patients with epilepsy are reported not to be fully adherent to their medication schedule. We aimed to conduct an economic evaluation of strategies for improving adherence to antiepileptic drugs. Based on the findings of a systematic review, we identified an implementation-intention intervention (specifying when, where and how to act) which was tested in a trial that closely resembled current clinical management of patients with epilepsy, and which measured adherence with an objective and least biased method. Using patient-level data, trial patients were matched to those recruited to the Standard And New Antiepileptic Drugs trial, according to their clinical characteristics and adherence. Generalised linear models were used to adjust cost and utility in order to estimate the incremental cost per quality-adjusted life-year (QALY) gained from the perspective of the National Health Service in the UK. The mean cost of the intervention group, £1,340 (95% CI £1,132, £1,688) was marginally lower than that of the control group representing standard care £1,352 (95% CI £1,132, £1,727). QALYs in the intervention group were higher than the control, 0.75 (95% CI 0.70, 0.79), compared with 0.74 (95% CI 0.68, 0.79), U"T that the intervention is cost effective at a threshold of £20,000 per QALY is 94%. Our analysis lends support to the cost-effectiveness of a self-directed, implementation-intention intervention for improving adherence to antiepileptic drugs. However, as with any modeling dependent on limited data on efficacy, there is considerable uncertainty surrounding the clinical effectiveness of the intervention which would require a substantive trial for a more definitive conclusion.

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

Cited by 53 publications

References 13 publications

Sudden unexpected death in epilepsy

Sudden unexpected death in epilepsy

Etiology and management of refractory epilepsies

Economic evaluation of a behavior-modifying intervention to enhance antiepileptic drug adherence

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