Depression is the most frequent psychiatric condition experienced in stroke survivors. Selective serotonin reuptake inhibitors (SSRIs) are frequently used as first‐line antidepressants; however, they have been strongly associated with hyponatremia which, in poststroke patients, can worsen outcomes. This study aims to determine and compare the incidence and magnitude of hyponatremia and potential risk factors in patients receiving either escitalopram or sertraline for the management of poststroke depression (PSD). A retrospective observational study involving all hospitalized patients who received either escitalopram or sertraline for the treatment of PSD. Electronic medical records were reviewed over a 5‐year period with data collected on various demographic, laboratory, comorbidity, and medication‐related variables. Data were analyzed using multivariate logistic regression. A total of 401 patients met the inclusion criteria. Overall, 36.7% of patients experienced hyponatremia, with 67 (38.3%) cases in patients receiving escitalopram and 76 (33.6%) in sertraline group. The median drop in sodium level from baseline was 5 mmol/L in both groups; with the majority of cases being of mild nature (73.1% and 69.7% for escitalopram and sertraline, respectively). Findings from the multivariate logistic regression did not yield a model with significant association (p = 0.353). Escitalopram and sertraline were both associated with an increased risk of hyponatremia in poststroke patients, with most cases being mild. There was no significant difference between treatment arms regarding the incidence or magnitude of hyponatremia. Caution should be exercised when prescribing escitalopram or sertraline.
