Second-Generation Antidepressants and Hyponatremia Risk: A Population-Based Cohort Study of Older Adults

• Published in: American journal of kidney diseases Vol. 69; no. 1; pp. 87 - 96
• Main Authors: Gandhi, Sonja, Shariff, Salimah Z., Al-Jaishi, Ahmed, Reiss, Jeffrey P., Mamdani, Muhammad M., Hackam, Daniel G., Li, Lihua, McArthur, Eric, Weir, Matthew A., Garg, Amit X.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2017
• Subjects: Aged; antidepressants; Antidepressive Agents, Second-Generation - adverse effects; anxiety disorder; citalopram; Cohort Studies; duloxetine; electrolyte disorder; escitalopram; Female; fluoxetine; fluvoxamine; Hospitalization - statistics & numerical data; Humans; Hyponatremia; Hyponatremia - chemically induced; Hyponatremia - epidemiology; Male; mirtazapine; mood disorder; Nephrology; older adults; paroxetine; Retrospective Studies; Risk Assessment; second-generation antidepressant; sertraline; serum sodium; syndrome of inappropriate antidiuretic hormone secretion (SIADH); Time Factors; venlafaxine; second-generation antidepressant; syndrome of inappropriate antidiuretic hormone secretion (SIADH); mirtazapine; Hyponatremia; mood disorder; antidepressants; fluvoxamine; serum sodium; paroxetine; fluoxetine; venlafaxine; older adults; escitalopram; duloxetine; anxiety disorder; electrolyte disorder; citalopram; sertraline
• ISSN: 0272-6386; 1523-6838; 1523-6838
• DOI: 10.1053/j.ajkd.2016.08.020

Hyponatremia may occur after initiation of a second-generation antidepressant drug. However, the magnitude of this risk among older adults in routine care is not well characterized. Retrospective, population-based, matched-cohort study. In Ontario, Canada, 2003 to 2012, we compared older adults with a mood or anxiety disorder who were dispensed 1 of 9 second-generation antidepressant drugs with matched adults with comparable indicators of baseline health who were not dispensed an antidepressant drug (n=138,246 per group). A similar comparison was made in a subpopulation with available laboratory data (n=4,186 per group). Second-generation antidepressant prescription versus no antidepressant prescription. The primary outcome was hospitalization with hyponatremia. A secondary outcome was hospitalization with both hyponatremia and delirium. We assessed hospitalization with hyponatremia using a diagnosis code and, in the subpopulation, serum sodium values. We assessed hospitalization with hyponatremia and delirium using a combination of diagnosis codes. Second-generation antidepressant use versus nonuse was associated with higher 30-day risk for hospitalization with hyponatremia (450/138,246 [0.33%] vs 84/138,246 [0.06%]; relative risk [RR], 5.46 [95% CI, 4.32-6.91]). This association was consistent in the subpopulation with serum sodium values (73/4,186 [1.74%] vs 18/4,186 [0.43%]; RR, 4.23 [95% CI, 2.50-7.19]; absolute risk increase, 1.31% [95% CI, 0.87%-1.75%]). Second-generation antidepressant use versus nonuse was also associated with higher 30-day risk for hospitalization with both hyponatremia and delirium (28/138,246 [0.02%] vs 7/138,246 [0.005%]; RR, 4.00 [95% CI, 1.75-9.16]). Measures of serum sodium could be ascertained in only a subpopulation. Use of a second-generation antidepressant in routine care by older adults is associated with an approximate 5-fold increase in 30-day risk for hospitalization with hyponatremia compared to nonuse. However, the absolute increase in 30-day incidence is low.