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. 2025 Aug;48(8):1707-1715.
doi: 10.1007/s40618-025-02587-4. Epub 2025 Apr 22.

Treatment with antidepressant drugs and hyponatremia: a network meta-analysis

Dario Norello  1   2 , Giuseppe Defazio  3   4 , Giovanni Corona  5 , Chiara Caiulo  6 , Mario Maggi  1   3 , Alessandro Peri  7   8   9   10
Affiliations

Treatment with antidepressant drugs and hyponatremia: a network meta-analysis

Dario Norello et al. J Endocrinol Invest. 2025 Aug.

Abstract

Objective: To evaluate the risk of hyponatremia during therapy with antidepressant drugs, in particular by investigating whether there is a different risk profile depending on the class or single active principles.

Methods: A meta-analysis was performed including all studies in which the risk of hyponatremia in subjects with or without antidepressant treatment was assessed. An extensive Medline, Embase and Cochrane search was performed, to retrieve all studies published up to February 5th 2024, using the following words: hyponatremia and antidepressant.

Results: Of 409 retrieved articles, 10 studies satisfied the inclusion criteria encompassing a total of 1,026,870 patients with 89,403 hyponatremic subjects. Treatments with selective serotonin reuptake inhibitors (OR = 3.31 [2.41;4.56], p < 0.01), serotonin-noradrenaline reuptake inhibitors (OR = 5.79 [1.27;26.49], p = 0.02) and tricyclic antidepressants (OR = 3.01 [1.27;7.14], p = 0.01) were found to be significantly associated with an increased risk of hyponatremia, whereas treatment with noradrenaline and specific serotonergic antidepressants was not. A network meta-analysis indicated that treatments with venlafaxine (OR = 5.99 [2.39;14.99], p < 0.01), paroxetine (OR = 4.93 [2.01;12.12], p < 0.01), sertraline (OR = 4.15 [1.98;8.70], p < 0.01), citalopram (OR = 3.49 [1.54;7.9], p < 0.01), escitalopram (OR = 3.49 [1.49;8.19], p < 0.01), fluoxetine (OR = 3.40 [1.13;10.21], p = 0.03) and mirtazapine (OR = 2.83 [1.16;6.92], p = 0.02) were found to be significantly associated with an increased risk of hyponatremia with a progressively decreasing OR. Clomipramine (OR = 4.50 [0.97;20.93], p = 0.05) also showed a trend towards a greater risk of hyponatremia. Otherwise, treatments with fluvoxamine, imipramine, maprotiline, amitriptyline and mianserin were not associated with an increased risk of hyponatremia.

Conclusions: These data appear useful on clinical grounds, in order to increase the awareness regarding the possibility that antidepressants induce hyponatremia and to encourage regular serum sodium monitoring.

Keywords: Antidepressants; Hyponatremia; Meta-analysis; Network; SIAD.

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Conflict of interest statement

Declarations. Conflict of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

References

    1. Upadhyay A, Jaber BL, Madias NE (2006) Incidence and prevalence of hyponatremia. Am J Med 119:30–35
    1. Hoorn EJ, Lindemans J, Zietse R (2006) Development of severe hyponatremia in hospitalized patients: treatment- related risk factors and inadequate management. Nephrol Dial Transpl 21(1):70–76
    1. Adrogue HJ, Madias NE, Hyponatremia (2000) N Engl J Med 342(21):1581–1589 - PubMed
    1. Ellison DH, Berl T (2007) Clinical practice. The syndrome of inappropriate antidiuresis. N Engl J Med 356(20):2064–2072 - PubMed
    1. Corona G, Norello D, Parenti G, Sforza A, Maggi M, Peri A (2018) Hyponatremia, falls and bone fractures: A systematic review and meta-analysis. Clin Endocrinol (Oxf) 89(4):505–513 - PubMed

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