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


Background — 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.

Methods — 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.

Results — 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).

Conclusions 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.



Dev V, Dixon SN, Fleet JL, Gandhi S, Gomes T, Harel Z, Jain AK, Shariff SZ, Tawadrous D, Weir MA, Garg AX. BMC Nephrol. 2014; 15:79. Epub 2014 May 10.

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