Nonadherence to antiepileptic drugs and increased mortality Findings from the RANSOM Study

UAB Epilepsy Center, Civitan International Research Center 312, 1719 6th Avenue South, Birmingham, AL 35294, USA.
Neurology (Impact Factor: 8.29). 06/2008; 71(20):1572-8. DOI: 10.1212/01.wnl.0000319693.10338.b9
Source: PubMed

ABSTRACT The primary objective was to investigate whether nonadherence to antiepileptic drugs (AEDs) is associated with increased mortality and the secondary objective to examine whether nonadherence increases the risk of serious clinical events, including emergency department (ED) visits, hospitalizations, motor vehicle accident (MVA) injuries, fractures, and head injuries.
A retrospective open-cohort design was employed using Medicaid claims data from Florida, Iowa, and New Jersey from January 1997 through June 2006. Patients aged > or =18 years with > or =1 diagnosis of epilepsy by a neurologist and > or =2 AED pharmacy dispensings were selected. Medication possession ratio (MPR) was used to evaluate AED adherence on a quarterly basis with MPR > or =0.80 considered adherent and <0.80 nonadherent. The association of nonadherence with mortality was assessed using a time-varying Cox regression model adjusting for demographic and clinical confounders. Incidence rates for serious clinical events were compared between adherent and nonadherent quarters using incidence rate ratios (IRRs) with 95% CIs calculated based on the Poisson distribution.
The 33,658 study patients contributed 388,564 AED-treated quarters (26% nonadherent). Nonadherence was associated with an over threefold increased risk of mortality compared to adherence (hazard ratio = 3.32, 95% CI = 3.11-3.54) after multivariate adjustments. Time periods of nonadherence were also associated with a significantly higher incidence of ED visits (IRR = 1.50, 95% CI = 1.49-1.52), hospital admissions (IRR = 1.86, 95% CI = 1.84-1.88), MVA injuries (IRR = 2.08, 95% CI = 1.81-2.39), and fractures (IRR = 1.21, 95% CI = 1.18-1.23) than periods of adherence.
These findings suggest that nonadherence to antiepileptic drugs can have serious or fatal consequences for patients with epilepsy.

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Available from: Annie Guerin, Aug 24, 2015
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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 with increased hospital admission rates [6]. While large cross-sectional studies have demonstrated substantial difference in health outcomes between patients with high adherence and patients with low adherence, prospective studies are lacking. "
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    ABSTRACT: Between 35% and 50% of patients with epilepsy are reported to be not 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 with those recruited for the Standard and New Antiepileptic Drugs trial according to their clinical characteristics and adherence. Generalized 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, £1340 (95% CI: £1132, £1688), was marginally lower than that of the control group representing standard care, £1352 (95% CI: £1132, £1727). Quality-adjusted life-year values in the intervention group were higher than those in the control group, i.e., 0.75 (95% CI: 0.70, 0.79) compared with 0.74 (95% CI: 0.68, 0.79), resulting in a cost saving of £12 (€15, US$19) and with the intervention being dominant. The probability 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. Copyright © 2015 Elsevier Inc. All rights reserved.
    Epilepsy & Behavior 03/2015; 45. DOI:10.1016/j.yebeh.2015.01.035 · 2.26 Impact Factor
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    • " Mortality was associated with having an injury in the previous year  OR: 1.41 Zielihski, 1974 (20)  In known epileptic patients, cause of death due to accidents (not due to seizure)  4.1% Faught et al, 2008 (25) Non adherence associated with 50% increase in fractures and motor-vehicle accidents "
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    ABSTRACT: Background Population-based studies have consistently found a two to three fold increase in mortality rates in patients with epilepsy (PWE) compared with the general population. The cause of this increase remains uncertain but several risk factors have been identified including non-adherence to medication, treatment for depression and alcohol abuse.
    02/2015, Degree: SSC MBBS, Supervisor: Leone Ridsdale
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    • "Adherence studies have been done in patients with other chronic diseases such as hypertension, heart disease, diabetes, arthritis, chronic obstructive pulmonary disease, asthma, depression, osteoporosis , and high cholesterol [3]. The medication possession ratio (MPR) is a measure of adherence frequently utilized in the literature [1]. It is calculated by dividing the number of days of medication supplied within the refill interval by the number of days in the refill interval. "
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    ABSTRACT: Rationale: Antiepileptic drugs are the mainstay of treatment for patients with epilepsy. Adherence to the prescribed regimen is a major factor in achieving a reduced seizure burden, which can decrease morbidity and mortality. Patients with epilepsy oftentimes complain about difficulty with memory. Because little is known about the relationship between memory and mood and adherence, the purpose of this project was to determine the impact of the confounding factors of memory and mood on antiepileptic drug adherence in patients with epilepsy. Methods: One hundred adult patients with epilepsy were recruited from the outpatient neurology clinic for this cross-sectional study. Patients who met the inclusion criteria completed measures of subjective memory (subset of 6 memory questions from the QOLIE-89) and objective memory (Hopkins Verbal Learning Test - Revised), subjective adherence (Morisky scale) and objective adherence (medication possession ratio), and mood (Neurological Disorders Depression Inventory for Epilepsy). Refill records from each patient's community pharmacy were used to objectively assess adherence. Medication possession ratios were calculated based on the antiepileptic drug refill records over the previous 6months. Patients were considered adherent if their MPR was >80%. Results: Women made up the majority of the sample (n=59), and, on average, patients had been living with epilepsy for nearly 20years. Approximately 40% of the sample were on antiepileptic drug monotherapy; most patients (>70%) took their antiepileptic drugs twice daily, and the mean number of total medications was 4.25±2.98. Based on the objective measure of adherence, 35% of the patients were nonadherent. Patients self-reported better adherence than what was objectively measured. Only the retention metric of the objective memory measure differentiated adherent patients from nonadherent patients. Patients in the adherent group had significantly lower depression scores (indicating better mood) compared with those in the nonadherent group (p=0.04). Conclusions: Objective memory measures were not robustly correlated with adherence. However, we observed that patients with higher depressed mood scores were more likely to be nonadherent. By targeting patients with epilepsy and comorbid depression, practitioners may identify patients at greatest risk of nonadherence and subsequent harm.
    Epilepsy & Behavior 01/2015; 43C:61-65. DOI:10.1016/j.yebeh.2014.11.017 · 2.26 Impact Factor
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