Hyponatraemia during psychopharmacological treatment: results of a drug surveillance programme

Int J Neuropsychopharmacol. 2012 Jul;15(6):739-48. doi: 10.1017/S1461145711001192. Epub 2011 Jul 22.


Hyponatraemia (HN) can be a life-threatening medical condition which may lead to severe neurological and psychiatric symptoms. The AMSP (Arzneimittelsicherheit in der Psychiatrie) is a multicentre drug surveillance programme that assesses severe or new adverse drug reactions during psychopharmacological treatment in psychiatric inpatients. We report on a total of 263 864 psychiatric inpatients monitored from 1993 to 2007 in 80 psychiatric hospitals in Germany, Switzerland and Austria. During this period plasma sodium levels below 130 mmol/l (severe HN according to AMSP) were reported in 93 patients (relative frequency 0.04%). On average, the plasma sodium levels of all cases were 119.7 mmol/l (±5.8 s.d.); median 121 mmol/l (range 104-129 mmol/l). Patients who showed no clinical signs (n=65, 70%) had a mean sodium level of 121.3 mmol/l (±5.0 s.d.); median 122 mmol/l (range 114-129 mmol/l). By contrast, patients with clinical symptoms (n=28, 30%) had a mean sodium level of 116.0 mmol/l (±6.0 s.d.); median 117 mmol/l (range 104-125 mmol/l). HN was mainly observed during treatment with selective serotonin reuptake inhibitors (SSRIs) (0.06%), Serotonin noradrenaline reuptake inhibitors (SNRIs) (0.08%), carbamazepine (0.10%) and oxcarbazepine (1.29%); the highest rate was found for oxcarbazepine. Antipsychotics, mirtazapine and tricyclic antidepressants were only rarely involved in HN (0.003-0.005%). Combinations of several drugs known to induce HN significantly increased the risk of HN, e.g. more than 10-fold for SSRI+diuretics+ACE inhibitors (0.37%) vs. SSRI given alone (0.02%). This is clinically relevant because such combinations, e.g. SSRI+diuretics may occur especially in elderly patients, who are in general at higher risk of developing HN.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adverse Drug Reaction Reporting Systems
  • Aged
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Hyponatremia / chemically induced*
  • Hyponatremia / epidemiology
  • Incidence
  • International Cooperation
  • Male
  • Mental Disorders / drug therapy
  • Mental Disorders / epidemiology
  • Middle Aged
  • Product Surveillance, Postmarketing
  • Retrospective Studies
  • Risk Factors
  • Sodium / blood


  • Antipsychotic Agents
  • Sodium