Association between antidepressant drug use and hyponatraemia: a case-control study

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To estimate the risk of, and risk factors for, hyponatraemia associated with the use of selective serotonin reuptake inhibitors (SSRIs) compared with the use of other antidepressant drugs.


A case-control study of psychiatric in- and out-patients on antidepressant drugs performed in the mid-southern part of The Netherlands over a 2 year period. Cases (n =29) were all using antidepressant drugs with a serum sodium concentration of ≤130 mmol l−1 while controls (n =78) were patients on antidepressants with a normal sodium concentration (136–144 mmol l−1). Information on blood sodium concentrations was obtained from clinical chemistry data while information on drug use was obtained from community and hospital pharmacy databases. Medical records were used to ascertain possible risk and confounding factors. Unconditional multivariate logistic regression was used to estimate odds ratios for hyponatraemia in patients on SSRIs compared with patients on other antidepressant drugs.


SSRIs were associated with an increased risk of hyponatraemia (OR 3.3; 95% CI 1.3, 8.6) compared with other classes of antidepressant drugs. Stratified and interaction analyses revealed that elderly patients using diuretics concomitantly with SSRIs were at the highest risk of experiencing hyponatraemia (OR 13.5; 95% CI 1.8, 101).


SSRIs are more frequently associated with hyponatraemia than other classes of antidepressant drugs. This adverse drug reaction was more common in older patients (≥65 years) and in those using diuretics.

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