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Published on: September 1, 2023
Incidence trends and risk factors for hyponatremia in epilepsy patients: A large-scale real-world data study
Yoshiaki Yamamoto1,2, Akiko Ohta1, Naotaka Usui1
1Department of Clinical Research, NHO, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Shizuoka, 420-8688, Japan.
Insights
Hyponatremia is a significant risk in epilepsy patients, particularly older adults, with certain medications increasing its incidence. Careful serum sodium monitoring is advised when using specific antiseizure and antipsychotic drugs.
Area of Science:
- Neurology
- Clinical Pharmacology
- Epidemiology
Background:
- Epilepsy affects diverse age groups, with a growing elderly population.
- Hyponatremia, a condition of low serum sodium, is a known complication in some patient populations.
- Understanding the incidence and risk factors of hyponatremia in epilepsy is crucial for patient safety.
Purpose of the Study:
- To determine the annual incidence of hyponatremia across pediatric, adult, and older adult epilepsy patient cohorts.
- To identify key risk factors associated with the development of hyponatremia in these epilepsy patient groups.
- To analyze trends in hyponatremia incidence over time within different age demographics.
Main Methods:
- A retrospective cohort study involving 26,179 epilepsy patients (pediatric, adult, older adult).
- Serum sodium levels were analyzed from January 2006 to December 2020.
- Moderate-to-severe hyponatremia was defined as serum sodium <130 mEq/L.
Main Results:
- Overall, 2.6% of patients developed moderate-to-severe hyponatremia.
- Incidence rates per 1000 person-years were 3.1 (pediatric), 19.8 (adult), and 50.4 (older adult).
- Significant risk factors included carbamazepine, valproate, phenytoin, phenobarbital, benzodiazepines, and antipsychotics; zonisamide showed a protective effect.
Conclusions:
- The incidence of hyponatremia is highest in older adult epilepsy patients and is increasing.
- Certain antiseizure medications and antipsychotics are significant risk factors, with some showing dose-dependent effects.
- Close monitoring of serum sodium is recommended, especially when using first-generation antiseizure medications or antipsychotics in epilepsy patients.
Objective:
This study aimed to evaluate the annual incidence and risk factors of hyponatremia in pediatric, adult, and older adult patients with epilepsy.
Methods:
We enrolled 26,179 patients: 8598 pediatric patients (aged 0-15 years), 16,476 adults (aged 16-64 years), and 1105 older adults (aged ≥65 years). Patients were included if their serum sodium levels were measured between January 2006 and December 2020. Moderate-severe hyponatremia was defined as a serum sodium level of less than 130 mEq/L.
Results:
From 2006 to 2020, 677 patients (2.6%) developed moderate-severe hyponatremia. The incidence of hyponatremia per 1000 person-years was 3.1 in the pediatric group, 19.8 in the adult group, and 50.4 in the older adult group. The incidence increased markedly from 36.8 in 2007 to 58.5 in 2020 in the older adult group but remained unchanged in the adult group and tended to decrease in the pediatric group. In the multiple logistic regression model, use of carbamazepine, valproate, phenytoin, phenobarbital, benzodiazepines, and antipsychotics was found to be a significant risk factor for hyponatremia. In adult patients, carbamazepine, benzodiazepine, and antipsychotics induced hyponatremia in a dose-dependent manner. Concomitant use of zonisamide reduced the risk of hyponatremia.
Significance:
Hyponatremia will become an increasingly important concern in clinical settings because the population of epilepsy patients is aging. Serum sodium levels should be monitored carefully when patients are receiving first-generation antiseizure medications or antipsychotics or combinations of these drugs. Our findings may help to minimize the risk of hyponatremia in epilepsy patients.
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