Clinical Lecturer in Neurology University of Michigan Ann Arbor, Michigan
This abstract is a recipient of the Gaps in Practice Research Award
Rationale: Patients with epilepsy experience a high degree of comorbidity. While comorbidity likely drives polypharmacy, scarce data exist describing the burden of polypharmacy in this high-risk population. Prior research has focused little attention on describing prevalence of medications aside from antiseizure medications (ASMs), has not well captured prevalence of drug-disease interactions (i.e., seizure-threshold lowering medications) or particularly relevant drug-drug combinations (i.e., black box warning combinations), and has not been nationally representative in the U.S. Holistically characterizing medication regimens is a critical step towards future investigation identifying inappropriate drug treatments and reducing adverse effects from complex central nervous system (CNS) polypharmacy. Methods: This was a retrospective cross-sectional study using data from the nationally representative National Health and Nutrition Examination Survey (NHANES). We included patients who reported taking at least one prescription medication in order to treat seizures or epilepsy during NHANES survey years 2013-2016. We assessed the number and predictors of prescribed medications using a negative binomial regression. We then assessed prevalence of polypharmacy (≥ 5 medications), CNS polypharmacy (≥ 3 CNS-acting medications) and additional CNS-acting medications, and drugs that lower the seizure threshold (i.e., bupropion and tramadol), and extrapolated prevalence to estimated affected U.S. population. Results: NHANES contained 20,146 participants; 135 met inclusion criteria representing 2,399,520 US citizens using NHANES’s sampling frame. Patients reported taking a mean 5.3 (95% CI: 4.3-6.3) prescription medications. Figure 1 shows the bivariate relationship between number of prescribed medications and age (A) or number of chronic conditions (B); adjusting for race, sex, and uninsurance, both age and number of chronic conditions predicted increased number of medications (IRR per decade: 1.16, 95% CI 1.04-1.28; IRR per chronic condition: 1.19, 95% CI 1.11-1.27). Table 1 demonstrates prevalence and extrapolated US population for each listed medication type or combination. Polypharmacy was reported by 47% (95% CI: 38%-57%) of patients, CNS polypharmacy by 34% (23%-47%), benzodiazepine use by 21% (14%-30%), opioid use by 16% (11%-24%), benzodiazepine plus opioid use by 6% (3%-14%), and 6% (2%-15%) reported a drug that lowers the seizure threshold. Twelve percent (7%-20%) took an opioid with either a benzodiazepine or gabapentinoid. Conclusions: Polypharmacy is common in patients with epilepsy. Patients taking antiseizure medications (ASMs) frequently reported also taking other CNS-acting medications (i.e., opioids, benzodiazepines, seizure threshold-lowering medications), and medication combinations with black box warnings. CNS polypharmacy poses health risks. Future research is needed to explore drivers of polypharmacy and strategies to help mitigate potentially harmful prescription use in this high-risk population. Funding: Please list any funding that was received in support of this abstract.: Dr Terman is supported by the University of Michigan Department of Neurology Training Grant 5T32NS007222-38. He has no relevant disclosures. Dr Aubert reports no funding. Dr Hill reports no funding. Dr Maust is supported by the National Institute on Drug Abuse R01DA045705. Dr Betjemann has received compensation for serving as web editor of JAMA Neurology and as a consultant to Marinus Pharmaceutics and the National Football League. Dr Boyd is supported by K24AG056578 and R24AG064025. Dr Burke is supported by National Institute of Neurological Disorders and Stroke K08 NS082597 and National Institutes of Health National Institute on Minority Health and Health Disparities R01 MD008879. Click here to view image/table
