Hyponatraemia (serum sodium arbitrarily defined as less than 135 mmol/L) is an increasingly recognised adverse effect of selective serotonin re-uptake inhibitors (SSRIs). Its precise prevalence and incidence in the elderly are hard to determine because of confounding factors including other prescribed medications and medical conditions. Although hyponatraemia has been reported with all SSRIs and venlafaxine, most studies are small, retrospective, limited by confounding variables or are individual case reports. The risk of developing hyponatraemia while on an SSRI seems to increase with age, female, sex, previous history of hyponatraemia and the concomitant use of other medications known to include hyponatraemia. The sodium concentrations of most patients with SSRI associated hyponatraemia return to normal within days to weeks of SSRI withdrawal. A few cases of SSRI rechallenge indicate that hyponatraemia may sometimes be a transient effect with tolerance developing over time. There is an urgent need for controlled, rigorous studies to confirm the extent of the association between SSRIs and hyponatraemia. Older drugs such as tricyclic antidepressants also need systematic study. It remains quite unclear whether any specific SSRI or venlafaxine has a stronger association with hyponatraemia than any other antidepressant drug.

SSRI and venlafaxine use is strongly associated with the presence of hyponatraemia in a population of elderly psychiatric inpatients and the association is not due to confounding by age, sex, depression status, medical illness severity or consumption of other drugs. Elderly patients on SSRIs or venlfaxine should have sodium levels checked before and after commencement of antidepressant treatment.