Antidepressants and the risk of hyponatremia: a Danish register-based population study

BMJ Open. 2016 May 18;6(5):e011200. doi: 10.1136/bmjopen-2016-011200.

Abstract

Objective: To examine the association between classes of antidepressants and hyponatremia, and between specific antidepressants and hyponatremia.

Design: Retrospective register-based cohort study using nationwide registers from 1998 to 2012.

Setting: The North Denmark Region.

Participants: In total, 638 352 individuals were included.

Primary and secondary outcome measures: Plasma sodium was obtained from the LABKA database. The primary outcome was hyponatremia defined as plasma sodium (p-sodium) below 135 mmol/L and secondary outcome was severe hyponatremia defined as p-sodium below 130 mmol/L. The association between use of specific antidepressants and hyponatremia was analysed using multivariable Poisson regression models.

Results: An event of hyponatremia occurred in 72 509 individuals and 11.36% (n=6476) of these events happened during treatment with antidepressants. Incidence rate ratios and CIs for the association with hyponatremia in the first p-sodium measured after initiation of treatment were for citalopram 7.8 (CI 7.42 to 8.20); clomipramine 4.93 (CI 2.72 to 8.94); duloxetine 2.05 (CI 1.44 to 292); venlafaxine 2.90 (CI 2.43 to 3.46); mirtazapine 2.95 (CI 2.71 to 3.21); and mianserin 0.90 (CI 0.71 to 1.14).

Conclusions: All antidepressants except mianserin are associated with hyponatremia. The association is strongest with citalopram and lowest with duloxetine, venlafaxine and mirtazapine.

Keywords: Hyponatremia.

MeSH terms

  • Adult
  • Aged
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Citalopram / therapeutic use
  • Clomipramine / therapeutic use
  • Denmark / epidemiology
  • Duloxetine Hydrochloride / therapeutic use
  • Female
  • Humans
  • Hyponatremia / blood
  • Hyponatremia / epidemiology*
  • Incidence
  • Male
  • Mianserin / analogs & derivatives
  • Mianserin / therapeutic use
  • Middle Aged
  • Mirtazapine
  • Registries
  • Retrospective Studies
  • Risk Factors
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Serotonin and Noradrenaline Reuptake Inhibitors / therapeutic use*
  • Sodium / blood
  • Venlafaxine Hydrochloride / therapeutic use

Substances

  • Antidepressive Agents, Tricyclic
  • Serotonin Uptake Inhibitors
  • Serotonin and Noradrenaline Reuptake Inhibitors
  • Citalopram
  • Mianserin
  • Venlafaxine Hydrochloride
  • Duloxetine Hydrochloride
  • Sodium
  • Mirtazapine
  • Clomipramine