Factors Associated with Hyponatremia in Patients Newly Prescribed Citalopram: A Retrospective Observational Study

BACKGROUND: Hyponatremia is a common and under-recognized adverse drug reaction of selective serotonin re-uptake inhibitor (SSRI) antidepressants. Despite its clinical importance, there are few large-scale studies on the factors associated with hyponatremia. OBJECTIVE: The aim of this study was to determine the incidence of hyponatremia and to identify patient factors associated with hyponatremia in a large, population-based cohort initiating new prescriptions for citalopram. METHODS: We included all patients with a new prescription for citalopram during 2010–2017, inclusive, with baseline and post-initiation serum sodium values available. Data were obtained from an Alberta Health Pharmacy database to identify new citalopram prescriptions. Laboratory values for patients with new prescriptions were obtained from linked Calgary Laboratory Services data. Incident hyponatremia was defined as serum sodium level < 135 mmol/L, following prescription initiation. Associations were determined by performing Cox regression with time-varying covariate analysis, with the development of hyponatremia as the dependent variable. RESULTS: A total of 19,679 patients with new prescriptions were identified; 12,842 females and 6837 males. The mean age was 55.48 years (SD 21.35). Of these patients, 3250 (16.5%) developed hyponatremia, 1996 (15.5% of) females and 1254 (18.3% of) males (p = 0.002). Cox regression showed significant associations of hyponatremia with lower baseline sodium (HR 0.788), older age (HR 1.029), thiazide diuretic use (HR 1.141), and male sex (HR 1.168). Pharmaceutical manufacturer or strength of citalopram did not have significant effects on the development of hyponatremia. CONCLUSION: This study provides additional data on the predictors of hyponatremia among patients initiating citalopram therapy. We report a 16.5% incidence of hyponatremia after starting citalopram treatment, and significant new findings include a higher incidence in males. This is the first published incidence of hyponatremia following the initiation of citalopram treatment across all ages in Canada.