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). CONCLUSION: 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.
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). CONCLUSION: 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: J Alderman; S H Preskorn; D J Greenblatt; W Harrison; D Penenberg; J Allison; M Chung Journal: J Clin Psychopharmacol Date: 1997-08 Impact factor: 3.153
Authors: John-Michael Sauer; Amanda J Long; Barbara Ring; Jennifer S Gillespie; Nathan P Sanburn; Karl A DeSante; David Petullo; Mark R VandenBranden; Charles B Jensen; Steven A Wrighton; Brian P Smith; Holly A Read; Jennifer W Witcher Journal: J Pharmacol Exp Ther Date: 2003-11-10 Impact factor: 4.030
Authors: Richard T Scheife; Lisa E Hines; Richard D Boyce; Sophie P Chung; Jeremiah D Momper; Christine D Sommer; Darrell R Abernethy; John R Horn; Stephen J Sklar; Samantha K Wong; Gretchen Jones; Mary L Brown; Amy J Grizzle; Susan Comes; Tricia Lee Wilkins; Clarissa Borst; Michael A Wittie; Daniel C Malone Journal: Drug Saf Date: 2015-02 Impact factor: 5.606
Authors: Martin A Katzman; Pierre Bleau; Pierre Blier; Pratap Chokka; Kevin Kjernisted; Michael Van Ameringen; Martin M Antony; Stéphane Bouchard; Alain Brunet; Martine Flament; Sophie Grigoriadis; Sandra Mendlowitz; Kieron O'Connor; Kiran Rabheru; Peggy M A Richter; Melisa Robichaud; John R Walker Journal: BMC Psychiatry Date: 2014-07-02 Impact factor: 3.630
Authors: Richard D Boyce; John R Horn; Oktie Hassanzadeh; Anita de Waard; Jodi Schneider; Joanne S Luciano; Majid Rastegar-Mojarad; Maria Liakata Journal: J Biomed Semantics Date: 2013-01-26
Authors: Gwenn S Smith; Hiroto Kuwabara; Neda F Gould; Najilla Nassery; Alena Savonenko; Jin Hui Joo; Kristin L Bigos; Michael Kraut; James Brasic; Daniel P Holt; Andrew W Hall; William B Mathews; Robert F Dannals; Ayon Nandi; Clifford I Workman Journal: Neuropharmacology Date: 2021-01-12 Impact factor: 5.273
Authors: Marijn Lijffijt; Nicholas Murphy; Sidra Iqbal; Charles E Green; Tabish Iqbal; Lee C Chang; Colin N Haile; Lorna C Hirsch; Nithya Ramakrishnan; Dylan A Fall; Alan C Swann; Rayan K Al Jurdi; Sanjay J Mathew Journal: Neuropsychopharmacology Date: 2021-11-27 Impact factor: 8.294