Presented by: David Nusbaum
University of Chicago Medical Center

Introduction

With expanding indications like treatment of alcohol dependence, obesity, and migraines, rates of topiramate and zonisamide prescription have increased in the United States. Given the effects that these medications have on urine chemistries, we conducted an observational study to estimate the risk of symptomatic stone events associated with their use.

Materials

We identified older adults enrolled in the United States’ largest health insurance program, Medicare, who were prescribed topiramate or zonisamide between 2008 and 2019, as well as age- and sex-matched controls. We then measured the frequency of symptomatic stone events (defined as an emergency department visit, hospitalization, or surgery for stones) in these two groups. Finally, we fit multivariate Cox proportional-hazards regression models to estimate the risk of a symptomatic stone event as a function of topiramate or zonisamide use, both overall and stratified by treatment indication.

Results

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A total of 237,217 patients met study inclusion criteria, including 39,518 who were prescribed topiramate or zonisamide. Unadjusted rates of symptomatic stone events occurred more frequently among topiramate and zonisamide users than controls during the three months to 9 years after their initial prescription fill (1.9% versus 0.8%, respectively [P<0.001]). After controlling for a variety of sociodemographic factors and level of comorbid illness, topiramate and zonisamide users had a 77% higher hazard (hazard ratio, 1.77 [95% confidence interval, 1.60 to 1.97]) than controls of a symptomatic stone event. When stratifying by treatment indication, this association persisted.

Conclusion

Regardless of treatment indication, topiramate and zonisamide use is associated with a higher hazard of a symptomatic stone event. Prescribing physicians and the patients for whom they care will need to determine whether the benefits of these medications are outweighed by their stone risk.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases

Lead Authors

Bassel Salka,
University of Michigan

Co-Authors

Mary Oerline,
University of Michigan

John Asplin,
Litholink Corporation

Vahakn Shahinian,
University of Michigan

John Hollingsworth,
NorthShore University HealthSystem