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

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.

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.

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.

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.