title: Antidepressants and the risk of hyponatremia: a class-by-class review of literature.
abstract: BACKGROUND
  Antidepressant-induced hyponatremia can cause significant morbidity and mortality. It is mostly associated with the use of selective serotonin reuptake inhibitors (SSRIs), but its frequency and class specificity are uncertain.
  
  
  OBJECTIVE
  To determine the relationship between hyponatremia and antidepressants and to define the incidence and odds ratios for antidepressant classes.
  
  
  METHODS
  A review of the literature prior to March 2013 was performed using Web of Science and PubMed by employing combinations of search strings "antidepressants" and antidepressant class and generic drug names with "hyponatr(a)emia," "SIADH," or "inappropriate ADH."
  
  
  RESULTS
  Overall, 21 effect studies and more than 100 case reports were considered, most concerning SSRIs. Because of variations in study designs, populations, and cutoff values, incidence rates diverged between 0.06% and 40% for SSRIs and 0.08% and 70% for venlafaxine. Although based on less solid evidence, incidence figures for mirtazapine and tricyclic antidepressants were lower. Regarding classes, odds ratios for SSRIs (1.5-21.6) were consistently higher than for tricyclic antidepressants (TCAs) (1.1-4.9). The risks associated with monoamine oxidase inhibitors, reboxetine, and bupropion could not be established owing to insufficient information. Patient risk factors included older age (odds ratios = 6.3) and concomitant use of (thiazide) diuretics (odds ratios = 11.2-13.5).
  
  
  CONCLUSIONS
  Hyponatremia is a potentially dangerous side effect of antidepressants and is not exclusive to SSRIs. Current evidence suggests a relatively higher risk of hyponatremia with SSRIs and venlafaxine, especially when combined with patient risk factors, warranting clinicians to be aware of this complication. The risks associated with mirtazapine are moderate, supporting this antidepressant as an alternative treatment for patients with (an increased risk of) hyponatremia.
authors.affiliation: Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine, University of Antwerp, Antwerp, Belgium; Psychopharmacological Research Unit, University Department of Psychiatry, Campus PZ Duffel, Antwerp, Belgium. Electronic address: livia.depicker@uantwerp.be.
authors.forename: Livia
authors.initials: L
authors.lastname: De Picker
authors.affiliation: Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine, University of Antwerp, Antwerp, Belgium; University Department of Psychiatry, Campus Antwerp University Hospital, Edegem, Antwerp, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Van Den Eede
authors.affiliation: Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine, University of Antwerp, Antwerp, Belgium; Psychopharmacological Research Unit, University Department of Psychiatry, Campus PZ Duffel, Antwerp, Belgium.
authors.forename: Glenn
authors.initials: G
authors.lastname: Dumont
authors.affiliation: Department of Internal Medicine, Antwerp University Hospital, Edegem, Antwerp, Belgium.
authors.forename: Greta
authors.initials: G
authors.lastname: Moorkens
authors.affiliation: Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine, University of Antwerp, Antwerp, Belgium; Psychopharmacological Research Unit, University Department of Psychiatry, Campus PZ Duffel, Antwerp, Belgium.
authors.forename: Bernard G C
authors.initials: BG
authors.lastname: Sabbe
mesh_terms: D000928:Antidepressive Agents / Q000009:adverse effects*; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects; D006801:Humans; D007010:Hyponatremia / Q000139:chemically induced*; D008803:Mianserin / Q000009:adverse effects / Q000031:analogs & derivatives; D000078785:Mirtazapine; D008996:Monoamine Oxidase Inhibitors / Q000009:adverse effects; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects; D000069470:Venlafaxine Hydrochloride / Q000009:adverse effects
chemical_list: D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D008803:Mianserin; D000078785:Mirtazapine; D008996:Monoamine Oxidase Inhibitors; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride