Time-dependent association between selective serotonin reuptake inhibitors and hospitalization due to hyponatremia

J Psychopharmacol. 2021 Aug;35(8):928-933. doi: 10.1177/02698811211001082. Epub 2021 Apr 16.


Background: Selective serotonin reuptake inhibitors (SSRIs) have a wide and increasing use for the treatment of depression and anxiety. Previous studies have indicated an increased risk of hyponatremia during the first months of treatment. We aimed to investigate the detailed time-course of SSRI-associated hyponatremia with a high temporal resolution, using registry data encompassing the total Swedish population.

Methods: This was a population-based case control study using several national registers. Patients hospitalized with a principal diagnosis of hyponatremia (n = 11,213) were compared with matched controls (n = 44,801). Multivariable regression was applied to explore time-dependent associations between SSRIs and hospitalization due to hyponatremia.

Results: Individuals initiating treatment with SSRIs were exposed to an immediately increased risk for hospitalization at week 1, reaching an adjusted odds ratio (aOR) (95% confidence interval) of 29 (19-46). The associations then gradually declined, reaching an aOR of 2.1 (1.0-4.2) by week 13. The aOR for individuals treated for longer than 13 weeks was 0.78 (0.71-0.85).

Conclusions: This study revealed a dramatically increased risk of hyponatremia exclusively related to newly initiated treatment. Consequently, even subtle symptoms consistent with hyponatremia during the first weeks of SSRI treatment should prompt analysis of sodium levels. In patients treated with SSRIs for several months or years, other causes should primarily be sought in the event of hyponatremia.

Keywords: SSRI; Syndrome of inappropriate antidiuretic hormone secretion; adverse reaction; hospitalization; hyponatremia; sodium.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Female
  • Hospitalization / statistics & numerical data*
  • Humans
  • Hyponatremia / epidemiology*
  • Hyponatremia / etiology
  • Male
  • Middle Aged
  • Registries
  • Retrospective Studies
  • Selective Serotonin Reuptake Inhibitors / administration & dosage
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Sweden
  • Time Factors
  • Young Adult


  • Serotonin Uptake Inhibitors