Differences in associations of antiepileptic drugs and hospitalization due to hyponatremia: A population-based case-control study.

Purpose: Hyponatremia induced by antiepileptic drugs is common, but detailed evidence is lacking. This can be problematic for the treating neurologist confronted with a patient with severe hyponatremia in need of an alternative drug. The objective of this study was to examine the association between individual antiepileptic drugs and hospitalization due to hyponatremia.

Methods: This was a register-based case-control study of patients in the general Swedish population. We included 14,359 individuals with a principal diagnosis of hyponatremia and 57,383 matched controls. The association between newly initiated (≤90 days) and ongoing antiepileptic treatment was investigated using multivariable logistic regression adjusting for concomitant drugs, medical conditions, previous hospitalizations and sociaoeconomic factors.

Results: For newly initiated antiepileptic drugs, adjusted ORs (95% CI) for hospitalization due to hyponatremia, compared to controls, were: carbamazepine 9.63 (6.18-15.33); phenytoin 4.83 (1.14-25.76); valproate 4.96 (2.44-10.66); lamotrigine 1.67 (0.70-4.08); levetiracetam 9.76 (4.02-27.59) and gabapentin 1.61 (1.08-2.38). Newly initiated oxcarbazepine treatment was only found in the hyponatremia group and not in controls. Adjusted ORs (CI) for individuals with ongoing treatment ranged from 7.97 (3.70-18.50) for oxcarbazepine to 0.83 (0.64-1.06) for gabapentin.

Conclusion: There was a strong association between newly initiated treatment with carbamazepine, oxcarbazepine and levetiracetam, and hospitalization due to hyponatremia. The corresponding association for phenytoin and valproate was moderate. The risk for hyponatremia was lower during ongoing treatment. Lamotrigine and gabapentin had the lowest risk both during initiation and ongoing treatment and may be advantageous in patients at risk of developing hyponatremia.