The Risk of Hyponatremia Across Different Classes of Antidepressants
10.22802/jksbtp.2025.31.1.1
- Author:
Ju Seong LEE
1
;
Sung Man CHANG
Author Information
1. Department of Psychiatry, Kyungpook National University Hospital, Daegu, Korea
- Publication Type:Review
- From:
Journal of the Korean Society of Biological Therapies in Psychiatry
2025;31(1):1-14
- CountryRepublic of Korea
- Language:English
-
Abstract:
Objectives:Unawareness of hyponatremic risks associated with antidepressant use can lead to irreversible consequences, such as syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Numerous previous studies on antidepressant-induced hyponatremia have reported a significant correlation between hyponatremia and the initiation of antidepressants. Although selective serotonin reuptake inhibitors (SSRIs) are most associated with hyponatremia, there is no consensus regarding the relationship between different classes of antidepressants and hyponatremia. The aim of this study is to investigate the correlation between different classes of antidepressants and hyponatremia by analyzing reported incidence rates and odds ratios (ORs).
Methods:This study reviewed literature available in both PubMed and Web of Knowledge using a combination of the search terms “antidepressants,” “hyponatremia,” “inappropriate ADH syndrome,” and “SSRI.”
Results:This study included 42 cohort and case-control studies, and more than 100 case reports were reviewed individually. Due to differences in study designs, populations, and definitions of hyponatremia, the reported incidence rate of hyponatremia associated with antidepressant use varied widely, ranging from 0.01% to 40%. Among antidepressant classes, serotonin norepinephrine reuptake inhibitors (SNRIs) exhibited the highest incidence rate (70%). Mirtazapine and tricyclic antidepressants (TCAs) were reported to have a comparatively lower risk of hyponatremia. Specifically, the OR ranged from 1.18 to 4.8 for mirtazapine and from 1.2 to 3.3 for TCAs. Many studies have agreed that geriatric age and concurrent use of diuretics, such as thiazides, are probable risk factors for hyponatremia.
Conclusions:Although awareness of antidepressant-associated hyponatremia has increased among healthcare providers, including clinicians, there is still no consensus on the extent of risk posed by different classes of antidepressants. Based on the reviewed studies, SNRIs appear to carry a higher risk of hyponatremia compared to other classes of antidepressants.Therefore, clinicians may consider prescribing mirtazapine, which has a lower risk of hyponatremia, as an alternative to SNRIs for certain patient populations—particularly elderly patients and those taking diuretics such as thiazides.
