Nonadherence to antiepileptic drugs and increased mortality: findings from the RANSOM study

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Faught E, Duh MS, Weiner JR, Guérin A, and Cunnington MC (2008) Nonadherence to antiepileptic drugs and increased mortality: findings from the ransom study. Neurology 71:20 1572–8.

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Abstract: OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: These findings suggest that nonadherence to antiepileptic drugs can have serious or fatal consequences for patients with epilepsy.



  • Retrospective study of morbidity and mortality due to nonadherence with AED regimens using data from 33,568 Medicaid patients. The proportion of days each quarter on which each patient possessed AED, based on prescription records, was used as a metric of adherence. Nonadherence was associated with increased mortality and more ED visits, hospital admissions, motor vehicle injuries, and fractures. It seems to difficult to eliminate potential confounds such as periods of financial stress that would affect both adherence and morbidity, though the authors note that participation in the Medicaid program should reduce cost barriers to medication access. Access to other medications should be influenced by similar cost considerations, but after controlling for adherence to other chronic medications in their multivariate model the Conclusions regarding AEDs were still valid. This article was a product of the Research on Antiepileptic Nonadherence and Selected Outcomes in Medicaid (RANSOM) study.


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