The association of selective serotonin reuptake inhibitors and venlafaxine with profound hyponatremia.

Background: Profound hyponatremia (plasma sodium <125 mmol/L) due to serotonergic antidepressants has mostly been addressed in small epidemiological studies. Given the potentially severe consequences of profound hyponatremia, there is a clear need to re-evaluate this risk in a larger cohort.

Aims: The aim of the study was to investigate the association of newly initiated selective serotonin reuptake inhibitors (SSRIs) or venlafaxine with profound hyponatremia.

Material and methods: The study was based on the Stockholm Sodium Cohort including health data on 1,632,249 individuals. First-time users of SSRI/venlafaxine who initiated treatment between 2007 and 2017 were included. We assessed the individual's plasma sodium concentration in relation to the drug usage with the individual as its own control.

Results: In total, 234,217 first-time users were included, and 3,999 individuals developed profound hyponatremia at least once. After initiation of SSRI/venlafaxine (baseline) the incidences of profound hyponatremia among individuals 65-79 and ≥80 years were 3% and 4%, respectively. Among individuals ≥80 years, the incidence was 6.5% for women and 3.4% for men. The adjusted odds ratio (aOR) for profound hyponatremia was 4.29 (95%CI 3.34-5.52) the first three months after SSRIs/venlafaxine initiation. After one year, the aOR was 1.30 (95%CI 0.97-1.75). During the first two weeks, the aOR was 10.06 (95%CI 5.97-17.00).

Conclusions: There was a strong association between newly initiated SSRI/venlafaxine and profound hyponatremia. The risk increased with age and female sex affecting 1 in 15 women ≥80 years. Consequently, heightened vigilance for hyponatremia is recommended following SSRI/venlafaxine initiation, particularly in elderly patients.