Does ASM Polypharmacy Impact Injury Risk Among Older Adults With Epilepsy?

ASM polypharmacy is associated with a higher risk for injury within 1-year of ASM prescription among older adults with epilepsy.

Most older adults with seizures receive an appropriate first prescription for antiseizure medication (ASM), and the risk for injury is associated with ASM polypharmacy. These are the findings of a retrospective cohort study published in Seizure: European Journal of Epilepsy.

The prevalence of seizures roughly doubles between the ages of 50 and 80 years. More than 95% of patients with epilepsy are treated with ASMs as they are effective at preventing recurrent seizures; however, older adults may be vulnerable to the side effects of ASMs.

Researchers from Icahn School of Medicine at Mount Sinai in the United States sourced data for this study from the MarketScan’s Commercial and Medicare Database. Adults (N=5,931) aged 50 years and older with newly diagnosed epilepsy or convulsion between 2015 and 2016, who received a minimum 30-day supply of ASMs within 1-year of diagnosis, were evaluated for injury within 1-year of ASM prescription.

The exposure of interest was whether patients received guideline recommended (eg, gabapentin, lamotrigine, levetiracetam, zonisamide), neutral (brivaracetam, carbamazepine, eslicarbazepine acetate, pregabalin, lacosamide, oxcarbazepine, topiramate, valproic acid), not recommended (cannabidiol, felbamate, phenobarbital, phenytoin, primidone, rufinamide, vigabatrin), or benzodiazepine ASMs.

Efforts to improve prescribing in older adults with epilepsy should consider both avoidance of potentially inappropriate therapies as well as avoidance of polytherapy.

The most common ASMs were levetiracetam (62.86%), gabapentin (11.73%), and phenytoin (4.45%).

Compared with patients without injury (n=3,828), those with injury at 1-year (n=2103) were older (P <.0001), received more ASM polypharmacy (P <.0001), they had a history of prior injury (P <.0001), and were more likely to have comorbidities, including Alzheimer disease and related dementia, stroke, and traumatic brain disorder (all P <.0001).

In the multivariate analysis, significant covariates of the association between ASM and injury included:

  • prior injury (hazard ratio [HR], 1.77; 95% CI, 1.59-1.97; P <.0001),
  • traumatic brain injury (TBI; HR, 1.55; 95% CI, 1.40-1.72; P <.0001),
  • ASM polypharmacy (HR, 1.32; 95% CI, 1.20-1.45; P <.0001),
  • age per 1-year increase (HR, 1.01; 95% CI, 1.01-1.01; P <.0001), and
  • Elixhauser Comorbidity Index per 1-point increase (HR, 1.01; 95% CI, 1.00-1.01; P =.013).

The 3 most common ASM polypharmacy combinations associated with injury risk were levetiracetam plus lorazepam, gabapentin, or lacosamide.

These findings may not be generalizable for current prescribing practices, as data were sourced from 2015-2016.

Overall, the researchers found that although most older adults who received an ASM for newly diagnosed epilepsy were given recommended treatments (eg, levetiracetam or gabapentin), the third most common prescription, phenytoin, was not recommended. These trends led the researchers to conclude, “Efforts to improve prescribing in older adults with epilepsy should consider both avoidance of potentially inappropriate therapies as well as avoidance of polytherapy.”

This article originally appeared on Neurology Advisor


Blank LJ, Agarwal P, Kwon C-S, Jetté N. Association of first antiseizure medication choice with injuries in older adults with newly diagnosed epilepsy. Seizure. Published online May 7, 2023. doi:10.1016/j.seizure.2023.05.006