[Antidepressive agents and hyponatremia: A literature review and a case/non-case study in the French Pharmacovigilance database]

Objective: Most antidepressants have been associated with a risk of hyponatremia in the literature. This effect is not always reported in monographs. The aim of our study was to clarify the difference of increased risk of hyponatremia among various antidepressants.

Methods: Retrospective study of such cases/non-cases from observations recorded in the French national pharmacovigilance between 01/01/2004 and 31/12/2013. We studied all antidepressants marketed in 2014 in France, with a positive control (haloperidol) and a negative one (amoxicillin). The association between exposure to a given drug and the occurrence of an adverse event was estimated by calculating the reporting odds ratio (ROR). His confidence interval (CI) was calculated with the method of Woolf, with an alpha risk of 5%. The disproportionality is defined by an ROR>1, the 95% CI did not include the value 1.

Results: Between 2004 and 2013, 3397 cases of hyponatremia were. All antidepressants were associated with hyponatremia among these cases, with the exception of: milnacipran, amoxapine, dosulepine, doxepine, trimipramine, iproniazide. The effect was predominant for the class of selective inhibitors of serotonin reuptake (SSRIs), inhibitors of serotonin reuptake and noradrenaline (SNRIs) and other antidepressants; it seemed more doubtful for tricyclic and monoamine oxidase inhibitors (MAOIs). Contrary to the literature, we found an association between hyponatremia and exposure to agomelatine (ROR=4.1, _95% CI [2.2 to 7.7]), mianserine (ROR=2.7, _95% CI [2.0 to 3.7]) and tianeptine (ROR=6.1, _95% CI [4.7 to 7.9]).

Conclusion: This study suggests to stay alert to electrolyte disorders when using all antidepressants, not only serotonin reuptake inhibitors.