title: A population-based assessment of the potential interaction between serotonin-specific reuptake inhibitors and digoxin.
abstract: OBJECTIVE
  In vitro evidence suggests that some serotonin-specific reuptake inhibitors (SSRIs) inhibit P-glycoprotein, a multidrug efflux pump responsible for the elimination of several drugs including digoxin. We sought to determine if some SSRIs cause digoxin toxicity in the clinical setting.
  
  
  METHODS
  Population-based nested case-control study set in Ontario, Canada from 1994 to 2001. We studied all patients 66 years or older treated with digoxin. Prescription and hospital admission records were analysed to determine the relationship between the initiation of SSRI therapy and hospital admission for digoxin toxicity in the subsequent 30 days.
  
  
  RESULTS
  Among 245 305 older patients treated with digoxin, we identified 3144 cases of digoxin toxicity. After adjusting for potential confounders, we observed an increased risk of digoxin toxicity following initiation of paroxetine [odds ratio (OR) 2.8; 95% confidence interval (CI) 1.6, 4.7], fluoxetine (OR 2.9; 95% CI 1.5, 5.4), sertraline (OR 3.0; 95% CI 1.9, 4.7), and fluvoxamine (OR 3.0; 95% CI 1.5, 5.7). However, an elevated risk was also seen with tricyclic antidepressants (OR 1.5; 95% CI 1.0, 2.4) and benzodiazepines (OR 2.1; 95% CI 1.7, 2.5), drugs classes having no known pharmacokinetic interaction with digoxin. There was no statistical difference in the risk of digoxin toxicity among any of the agents tested.
  
  
  CONCLUSIONS
  We found no major discrepancy in the risk of digoxin toxicity after initiation of various SSRI antidepressants, suggesting that the inhibition of P-glycoprotein by sertraline and paroxetine observed in vitro is unlikely to be of major clinical significance.
authors.affiliation: Clinical Epidemiology and Healthcare Research Program, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. dnj@uces.on.ca
authors.forename: David N
authors.initials: DN
authors.lastname: Juurlink
authors.forename: Muhammad M
authors.initials: MM
authors.lastname: Mamdani
authors.forename: Alexander
authors.initials: A
authors.lastname: Kopp
authors.forename: Nathan
authors.initials: N
authors.lastname: Herrmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Laupacis
mesh_terms: D000368:Aged; D000929:Antidepressive Agents, Tricyclic; D016022:Case-Control Studies; D000075202:Contraindications; D004077:Digoxin / Q000009:adverse effects*; D004347:Drug Interactions; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors
chemical_list: D000929:Antidepressive Agents, Tricyclic; D004077:Digoxin; D017367:Selective Serotonin Reuptake Inhibitors