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Higher anti-depressant dose and major adverse outcomes in moderate chronic kidney disease: a retrospective population-based study

Varun Dev1, Stephanie N Dixon1234, Jamie L Fleet2, Sonja Gandhi123, Tara Gomes456, Ziv Harel7, Arsh K Jain123, Salimah Z Shariff14, Davy Tawadrous12, Matthew A Weir123 and Amit X Garg12348*

Author Affiliations

1 Schulich School of Medicine, Western University, London, Canada

2 Division of Nephrology, Western University, London, Ontario, Canada

3 Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada

4 Institute for Clinical Evaluative Sciences, Ontario, Canada

5 Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada

6 Keenan Research Centre, Li Ka Shing Knowledge Institute, Toronto, Ontario, Canada

7 Division of Nephrology, University of Toronto, Toronto, Ontario, Canada

8 London Kidney Clinical Research Unit, Room ELL-101, London Health Sciences Centre, 800 Commissioners Road East, London, Ontario N6A 4G5, Canada

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BMC Nephrology 2014, 15:79  doi:10.1186/1471-2369-15-79

Published: 10 May 2014



Many older patients have chronic kidney disease (CKD), and a lower dose of anti-depressants paroxetine, mirtazapine and venlafaxine is recommended in patients with CKD to prevent drug accumulation from reduced elimination. Using information available in large population-based healthcare administrative databases, we conducted this study to determine if ignoring the recommendation and prescribing a higher versus lower dose of anti-depressants associates with a higher risk of adverse events.


We conducted a population-based cohort study to describe the 30-day risk of delirium in older adults who initiated a higher vs. lower dose of these three anti-depressants in routine care. We defined delirium using the best proxy available in our data sources - hospitalization with an urgent head computed tomography (CT) scan. We determined if CKD status modified the association between anti-depressant dose and outcome, and examined the secondary outcome of 30 day all-cause mortality. We used multivariable logistic regression analyses to estimate adjusted odds ratios (relative risk (RR)) and 95% confidence intervals.


We identified adults (mean age 75) in Ontario who started a new study anti-depressant at a higher dose (n = 36,651; 31%) or lower dose (n = 81,160; 69%). Initiating a higher vs. lower dose was not associated with an increased risk of hospitalization with head CT (1.09% vs. 1.27% (adjusted RR 0.90; 95% CI, 0.80 to 1.02), but was associated with a lower risk of all-cause mortality (0.76% vs. 0.97% RR 0.82; 95% CI, 0.71 to 0.95). Neither of these relative risks were modified by the presence of CKD (p = 0.16, 0.68, respectively).


We did not observe an increase in two adverse outcomes when study anti-depressants were initiated at a higher dose in elderly patients with moderate CKD. Contrary to our hypothesis, the 30-day risk of mortality was lower when a higher versus lower dose of anti-depressant was initiated in these patients, a finding which requires corroboration and further study.

Anti-depressant; Delirium; Aged; Chronic renal insufficiency; Cohort studies; Risk