title: Age-related changes in antidepressant pharmacokinetics and potential drug-drug interactions: a comparison of evidence-based literature and package insert information.
abstract: BACKGROUND
  Antidepressants are among the most commonly prescribed psychotropic agents for older patients. Little is known about the best source of pharmacotherapy information to consult about key factors necessary to safely prescribe these medications to older patients.
  
  
  OBJECTIVE
  The objective of this study was to synthesize and contrast information in the package insert (PI) with information found in the scientific literature about age-related changes of antidepressants in systemic clearance and potential pharmacokinetic drug-drug interactions (DDIs).
  
  
  METHODS
  A comprehensive search of two databases (MEDLINE and EMBASE from January 1, 1975 to September 30, 2011) with the use of a combination of search terms (antidepressants, pharmacokinetics, and drug interactions) was conducted to identify relevant English language articles. This information was independently reviewed by two researchers and synthesized into tables. These same two researchers examined the most up-to-date PIs for the 26 agents available at the time of the study to abstract quantitative information about age-related decline in systemic clearance and potential DDIs. The agreement between the two information sources was tested with κ statistics.
  
  
  RESULTS
  The literature reported age-related clearance changes for 13 antidepressants, whereas the PIs only had evidence about 4 antidepressants (κ < 0.4). Similarly, the literature identified 45 medications that could potentially interact with a specific antidepressant, whereas the PIs only provided evidence about 12 potential medication-antidepressant DDIs (κ < 0.4).
  
  
  CONCLUSIONS
  The evidence-based literature compared with PIs is the most complete pharmacotherapy information source about both age-related clearance changes and pharmacokinetic DDIs with antidepressants. Future rigorously designed observational studies are needed to examine the combined risk of antidepressants with age-related decline in clearance and potential DDIs on important health outcomes such as falls and fractures in older patients.
authors.affiliation: Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Boyce
authors.forename: Steven M
authors.initials: SM
authors.lastname: Handler
authors.forename: Jordan F
authors.initials: JF
authors.lastname: Karp
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Hanlon
mesh_terms: D000367:Age Factors; D000368:Aged; D000928:Antidepressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D004345:Drug Industry; D004347:Drug Interactions; D004348:Drug Labeling / Q000706:statistics & numerical data*; D019317:Evidence-Based Medicine; D006801:Humans
chemical_list: D000928:Antidepressive Agents