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.