title: Higher anti-depressant dose and major adverse outcomes in moderate chronic kidney disease: a retrospective population-based study.
abstract: 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.
authors.forename: Varun
authors.initials: V
authors.lastname: Dev
authors.forename: Stephanie N
authors.initials: SN
authors.lastname: Dixon
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Fleet
authors.forename: Sonja
authors.initials: S
authors.lastname: Gandhi
authors.forename: Tara
authors.initials: T
authors.lastname: Gomes
authors.forename: Ziv
authors.initials: Z
authors.lastname: Harel
authors.forename: Arsh K
authors.initials: AK
authors.lastname: Jain
authors.forename: Salimah Z
authors.initials: SZ
authors.lastname: Shariff
authors.forename: Davy
authors.initials: D
authors.lastname: Tawadrous
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Weir
authors.affiliation: Schulich School of Medicine, Western University, London, Canada. amit.garg@lhsc.on.ca.
authors.forename: Amit X
authors.initials: AX
authors.lastname: Garg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015897:Comorbidity; D003693:Delirium / Q000139:chemically induced / Q000401:mortality*; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology / Q000401:mortality*; D005260:Female; D017052:Hospital Mortality; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D009864:Ontario / Q000453:epidemiology; D051436:Renal Insufficiency, Chronic / Q000401:mortality*; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents