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Antidepressant Drug-Drug Interactions: Clinical Relevance and Risk Management

Published online by Cambridge University Press:  07 November 2014

Charles B. Nemeroff ,
Sheldon H. Preskorn  and
C. Lindsay DeVane
Charles B. Nemeroff
Affiliation:
Dr. Nemeroff is Reunette W. Harris Professor and Chairman of the Department of Psychiatry and Behavioral Sciences at Emory University School of Medicine in Atlanta, Georgia. Dr. Nemeroff is a currently on the scientific advisory boards of Forest, Janssen/Ortho-McNeil, Quintiles, and NeuroPharmaboost; receives grant/research support from the American Foundation for Suicide Prevention, the National Alliance for Research on Schizophrenia and Depression, and the National Institute of Mental Health (NIMH); and is a major stockholder or owns equity in Corcept, CeNeRx, Revaax, and NovaDel.
Sheldon H. Preskorn
Affiliation:
Dr. Preskorn is Professor and Chair of Psychiatry and BehavioralSciences at the University of Kansas School of Medicine, and president and chief executive officer of the Clinical Research Institute in Wichita, Kansas. Dr. Preskorn is a consultant to Bristol-Myers Squibb, Comentis, Cyberonics, Eisai, Eli Lilly, EnVivo, Evotec, Johnson & Johnson, Memory, Otsuka, Pfizer, Predix, Shire, Somerset, and Wyeth; is on the advisory boards of Bristol-Myers Squibb, Eli Lilly, Johnson & Johnson, Pfizer, Shire, Somerset, and Wyeth; is on the speaker's bureaus of Bristol-Myers Squibb, Cyberonics, Forest, Otsuka, and Pfizer; and receives grants/research support from Bristol-Myers Squibb, Comentis, Cyberonics, Johnson & Johnson, Merck, Memory, the NIMH, Novartis, Organon, Otsuka, Pfizer, Predix, Sepracor, Somerset, and Wyeth.
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Abstract

Multiple medication use is a common phenomenon, especially in patients with comorbid conditions and those treated with psychiatric drugs such as antidepressants. Combination treatment may result in potentially harmful drug-drug interactions (DDIs). Results of DDIs range from nuisance side effects to serious adverse consequences. DDIs may also result in improved efficacy. Augmentation strategies, for example, are intentional therapeutic DDIs. Pharmacokinetic DDIs occur when a second drug alters the absorption, distribution, metabolism, or clearance of the first drug. Research has concentrated on the relative effects of antidepressants on cytochrome P450 enzymes and, more recently, on drug transporters as potential mediators of clinically important pharmacokinetic DDIs. The most common, clinically relevant pharmacokinetic DDIs involve alteration in oxidative drug metabolism. Pharmacodynamic DDIs occur when the effects of a second drug quantitatively or qualitatively alters those of the first drug. Pharmacodynamic DDIs are not typically studied in vivo because of the potential for a serious adverse effect. All antidepressants can interact pharmacodynamically with certain other drugs. The risk of harmful DDIs can be reduced by recognizing variables that affect dose-concentration-effect relationships. It is important for physicians to weigh the risks and benefits of potential DDIs against the risks that accompany timid or ineffective disease treatment.

Type
Research Article
Information
CNS Spectrums , Volume 12 , Issue S7 , 2007 , pp. 1 - 16
Copyright
Copyright © Cambridge University Press 2007

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