Epilepsy affects about 1 % of people and is mainly treated with anti-seizure medication (ASM). The use of carbamazepine (CBZ) and oxcarbazepine (OXC) as first-line ASM in treating focal epilepsy is limited by hyponatremia. This thesis describes the association between CBZ or OXC and hyponatremia and the clinical impact that carbamazepine- and oxcarbazepine-induced hyponatremia (COIH) has on people with epilepsy.
We assessed the occurrence of COIH in a large cohort of people with epilepsy and looked for possible determinants. Over 2,600 people were included from our tertiary epilepsy centre in the Netherlands, and we collected data on sodium level measurements in people who (had) used CBZ and OXC. Our main finding was that hyponatremia (Na+ ≤134 mmol/L) occurred in about a quarter of those taking CBZ and almost half of those taking OXC, in line with other studies. Severe hyponatremia (Na+ ≤128 mmol/L) occurred in 7% in the CBZ group and 22% in the OXC group. Age over 40 years, high serum levels of CBZ and OXC and concomitant use of other ASMs were the main risk factors for hyponatremia in both treatment groups. Females on OXC were at a higher risk of hyponatremia than males. Symptoms present at hyponatremia, which could not be explained by another clear cause such as overt ASM intoxication or comorbidity were scored and found in almost half of people who had COIH. They lead to hospital admissions in 3%, primarily because of falls.
Next we assessed the AEs experienced by people taking CBZ or OXC and whether they could be attributed to COIH. We performed an observational retrospective study collecting data between 2017 and 2019 on serum sodium levels and AEs in 410 people with COIH and 300 with normal sodium levels from our previously described cohort. Our main finding was the occurrence of AEs in 65% of people with hyponatremia compared to 21% with normal sodium levels (OR 7,5, p=