Hyponatremia risk with antidepressant use: A retrospective study

Serotonergic antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), are associated with an increased risk of hyponatremia, whereas mirtazapine appears to confer a lower risk. However, evidence regarding newer antidepressants, specifically agomelatine, remains limited. This study aimed to evaluate the risk of hyponatremia associated with agomelatine compared with mirtazapine, escitalopram, and venlafaxine.

This retrospective cohort study analyzed electronic medical records from Kaohsiung Veterans General Hospital. Antidepressant-naïve patients who initiated at least 2 weeks of monotherapy with agomelatine, escitalopram, venlafaxine, or mirtazapine between May 2013 and April 2023 were included. Hyponatremia was identified using serum sodium measurements. Multivariable logistic regression was performed to assess the association between antidepressant use and hyponatremia after adjusting for demographic, clinical, and medication-related factors.

The incidence rates of hyponatremia were 5.8% for mirtazapine, 6.9% for agomelatine, 8.5% for escitalopram, and 10.2% for venlafaxine. In the univariate analysis, venlafaxine was associated with a higher risk of hyponatremia than was mirtazapine (odds ratio [OR] = 1.80, 95% CI: 1.09-2.97, p = 0.021). However, after adjustment, the risk of hyponatremia did not differ significantly among the antidepressants (agomelatine: adjusted odds ratio [aOR] = 0.79, escitalopram: aOR = 1.18, venlafaxine: aOR = 0.87; all p > 0.05). Independent predictors of hyponatremia included older age (aOR = 1.02, p < 0.001), malignancy (aOR = 2.52, p < 0.001), diabetes mellitus (aOR = 1.64, p < 0.001), and concomitant use of anticancer agents (aOR = 2.72, p < 0.001).

These findings underscore the complexity of hyponatremia etiologies and highlight the need for individualized treatment strategies that account for comorbidities and potential drug interactions.