Antiepileptic drugs and hyponatremia in older adults: Two population-based cohort studies

To examine the 30-day risk of hospitalization with hyponatremia associated with carbamazepine, valproic acid (V), phenytoin (P), or topiramate (T) use compared to nonuse in the outpatient setting among older adults.

We conducted two population-based, retrospective cohort studies in Ontario, Canada, between 2003 and 2015 using administrative health care databases of older adults. The first study compared carbamazepine users to a propensity-score matched group of antiepileptic drug nonusers, whereas the second compared V-P-T users to a propensity-score matched group of antiepileptic nonusers. The primary outcome was hospitalization with hyponatremia within 30 days of an antiepileptic prescription.

The baseline characteristics between matched groups were similar in both cohorts. Carbamazepine use versus nonuse was associated with a higher 30-day risk of hospitalization with hyponatremia (82/21,191 [0.39%] versus 30/63,573 [0.05%]; relative risk [RR] 8.20, 95% confidence interval [CI] 5.40-12.46). Similarly, V-P-T use versus nonuse was associated with a higher 30-day risk of hospitalization with hyponatremia (34/20,155 [0.17%] versus 26/40,310 [0.06%]; RR 2.62, 95% CI 1.57-4.36).

Older adults prescribed carbamazepine and V-P-T have a higher risk of being hospitalized with hyponatremia compared to other adults with similar indicators of baseline health who were not prescribed antiepileptic drugs. Physicians should be mindful of this risk; when a patient presents to a hospital with symptomatic hyponatremia these drugs should be considered as potential causes.