Second-Generation Antidepressants and Hyponatremia Risk: A Population-Based Cohort Study of Older Adults  Sonja Gandhi, PhD, Salimah Z. Shariff, PhD, Ahmed Al-Jaishi, MSc, Jeffrey P. Reiss, MD, Muhammad M. Mamdani, PharmD, MA, MPH, Daniel G. Hackam, MD, PhD, Lihua Li, MSc, Eric McArthur, MSc, Matthew A. Weir, MD, Amit X. Garg, MD, PhD  American Journal of Kidney Diseases  Volume 69, Issue 1, Pages 87-96 (January 2017) DOI: 10.1053/j.ajkd.2016.08.020 Copyright © 2016 National Kidney Foundation, Inc. Terms and Conditions

Figure 1 The association between antidepressant use and hospitalization with hyponatremia assessed in 5 subgroups: Antidepressant medication type, antidepressant medication dose, chronic kidney disease, congestive heart failure, and use of a diuretic. Sets of medication users and nonusers were matched on the presence of chronic kidney disease, congestive heart failure, and baseline diuretic use. For antidepressant medication type and dose, matched sets were categorized according to this characteristic in medication users. †Hyponatremia (and the proportion of patients who had an event) was assessed by using a hospital diagnosis code. The true event rate of hyponatremia is underestimated for some outcomes because the code for hyponatremia has high specificity but low sensitivity. ‡Fluoxetine, fluvoxamine, duloxetine, and venlafaxine were included in the tests for interactions but were removed from presentation because there were too few events for meaningful analysis. This was also done to comply with privacy regulations, to prevent the risk of reidentification when the size of the numerator is small (≤5). §Higher dose was defined as a higher than median daily dose. See Table S1 for definitions. Fluoxetine was not considered in the assessment of higher versus normal dose because a higher than median daily dose could not be accurately defined. ‖Chronic kidney disease was identified by using an algorithm of hospital diagnosis codes validated for older adults in the study region.36 The algorithm identified patients with a median estimated glomerular filtration rate of 38 (interquartile range, 27-52) mL/min/1.73m2, whereas its absence identified patients with a median estimated glomerular filtration rate of 69 (interquartile range, 56-82) mL/min/1.73m2. ¶Congestive heart failure has sensitivity, specificity, and positive predictive value of 84.3, 85.4, and 35.8%, respectively.37 ∗∗Diuretic use includes potassium-sparing and non–potassium-sparing medications. Abbreviation: CI, confidence interval. American Journal of Kidney Diseases 2017 69, 87-96DOI: (10.1053/j.ajkd.2016.08.020) Copyright © 2016 National Kidney Foundation, Inc. Terms and Conditions