Work

The Risk of Antidepressant-induced Hyponatremia: a Meta- Analysis of Antidepressant Classes and Compounds

Year: 2025

Type: article

Study designs: Systematic Review, Meta-Analysis

Abstract: Background Hyponatremia (hypoNa) is a potentially serious adverse event of treatment with antidepressants. Previous research suggests that risk of drug-induced hyponatremia differs between antidepressants.1 This meta-analysis sought to determine the risk of antidepressant-induced hypoNa, stratified by different compounds and classes. Methods PubMed and Web of Science were searched for studies reporting on incidence or risk of hypoNa in adults using antidepressants (PROSPERO, CRD42021269801). We modelled random-effects meta- analyses to compute overall incidence and risk of any and clinically relevant hypoNa for each compound and class, and ran head-to-head comparisons based on hypoNa incidences. We conducted subgroup analyses for geriatric populations, study context and sodium cut-off value. Results We included 39 studies (n = 8,175,125). Exposure to antidepressants was associated with significantly increased odds of hypoNa (k = 7 studies, OR = 3.160 (1.911-5.225)). The highest event rates were found for SNRIs (5.31%), SSRIs (5.18%), and TCAs (2.18%); the lowest for mirtazapine (1.02%) and trazodone (0.89%). The highest odds ratios were found for MAOIs (3.789 (1.602 – 8.966)), SNRIs (2.969 (1.717 – 5.136)), and SSRIs (2.842 (1.564 – 5.164)); the lowest for mirtazapine (2.818 (1.886 – 4.211)) and TCAs (1.803 (1.252 – 2.598)). Compared to SSRIs, SNRIs were significantly more likely (k = 9, OR = 1.268 (1.129 – 1.425), p <0.001) and mirtazapine significantly less likely (k = 9, OR = 0.607 (0.385 – 0.957), p = 0.032) associated with hypoNa. Conclusion Our meta-analysis demonstrated that, while no antidepressant can be considered completely risk-free, for hypoNa-prone patients mirtazapine should be considered the treatment of choice and SNRIs should be prescribed more cautiously than SSRIs and TCAs. References 1.De Picker L, Van den Eede F, Dumont G, Moorke G, Sabbe BGC. Antidepressants and the Risk of Hyponatremia: A Class-by-Class Review of Literature. Psychosomatics. 2014;55(6):536-47.

Source: The International Journal of Neuropsychopharmacology

DOI: 10.1093/ijnp/pyae059.034

Authors: Tim Gheysens, Filip Van Den Eede, *Livia De Picker

Institutions: University of Antwerp, Antwerp University Hospital

Language: English

Topic: Electrolyte and hormonal disorders

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,693