Background: Selective Serotonin Reuptake Inhibitors (SSRIs) have become the mainstay of treatment for
depression, anxiety, and many other conditions. However, they have been associated with an increased risk of
hyponatremia. Little is known about the risk of SSRI-associated hyponatremia in certain potentially at-risk populations,
such as patients with acute medical illnesses.
Objective: The main objective of this study was to examine the effect of SSRIs on serum sodium levels in medically-ill
Method: We performed a retrospective cohort study of 239 medically-ill inpatients assessed by the psychiatric
consultation-liaison team of a large Canadian academic hospital between 2008 and 2014. We grouped patients based on
whether they were exposed to an SSRI, a non-SSRI antidepressant, or no antidepressant at all. Our primary outcome was
the maximum decrease in serum sodium level observed within 30 days of antidepressant exposure in the inpatient setting.
Our secondary outcome was the incidence of hyponatremia (serum sodium level <135 mEq/L) or severe hyponatremia
(sodium level <130 mEq/L) within the same time frame.
Results: The maximum decrease in sodium serum level from baseline did not differ between the 3 groups studied (SSRIs -
3.31 mEq/L vs non-SSRI antidepressants -3.41 mEq/L vs no antidepressants -3.13 mEq/L, F (2) = 0.79, p= 0.92). The
incidence of hyponatremia and severe hyponatremia did not differ between groups either. This remained the case after
controlling for covariates.
Conclusion: SSRIs do not appear to be associated with an increased risk of hyponatremia in medically-ill inpatients.
Clinicians should not avoid prescribing SSRIs in this population based solely on the assumption of hyponatremia risk.