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


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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    • "For example, two studies using the Medical Events Monitoring System (MEMS)—a pill bottle with an electronic cap that records each time the bottle is opened—found that 76% of doses were taken overall [10], and 48% of patients took one-third or fewer of the prescribed AED doses [11]. Poor adherence affects important treatment outcomes such as numbers of hospital admissions, inpatient treatment days, emergency room visits, and health-care costs [12] [13]. Nonadherent patients report more uncontrolled seizures leading to greater epilepsy-related morbidity and mortality compared with adherent patients. "
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    ABSTRACT: Purpose: Medication nonadherence is one of the most important reasons for treatment failure in patients with epilepsy. The present study investigated the effectiveness of a multicomponent intervention to improve adherence to antiepileptic drug (AED) medication in patients with epilepsy. Methods: In a prospective, randomized multicenter trial, three sessions of face-to-face motivational interviewing (MI) in combination with complementary behavior change techniques were compared with standard care. Motivational interviewing prompted change talk and self-motivated statements from the patients, planning their own medication intake regimen and also identifying and overcoming barriers that may prevent adherence. Participants were provided with calendars to self-monitor their medication taking behavior. A family member and the health-care team were invited to attend the last session of MI in order to improve the collaboration and communication between patients, their caregiver or family member, and their health-care provider. At baseline and 6-month follow-up, psychosocial variables and medical adherence were assessed. Results: In total, 275 participants were included in the study. Compared with the active control group, patients in the intervention group reported significantly higher medication adherence, as well as stronger intention and perceptions of control for taking medication regularly. The intervention group also reported higher levels of action planning, coping planning, self-monitoring, and lower medication concerns. Conclusions: This study shows that MI can be effective in clinical practice to improve medication adherence in patients with epilepsy. It also provides evidence that combining volitional interventions, including action planning, coping planning, and self-monitoring with motivational interviewing can promote the effectiveness of the medical treatments for epilepsy by improving adherence.
    Full-text · Article · Sep 2015 · Epilepsy & Behavior
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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.
    Full-text · Article · Mar 2015 · Epilepsy & Behavior
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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.
    Full-text · Thesis · Feb 2015
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