Pharmacokinetic and pharmacodynamic interactions between antiepileptics and antidepressants

Domenico Italiano, Edoardo Spina, Jose De Leon

Research output: Contribution to journalReview articlepeer-review

47 Scopus citations

Abstract

Introduction: Antiepileptic-antidepressant combinations are frequently used by clinicians; their pharmacokinetic (PK) and pharmacodynamic (PD) drug interactions (DIs) have not been well studied but are frequently likely to be clinically relevant. Areas covered: This article provides a comprehensive review of PK DIs between antiepileptics and antidepressants. In the absence of PD DI studies, PD information on pharmacological mechanisms and studies on efficacy and safety of individual drugs are reviewed. Expert opinion: The clinical relevance of the inductive properties of carbamazepine, phenytoin, phenobarbital and primidone and the inhibitory properties of valproic acid and some antidepressants are well understood; correction factors are provided if appropriate DI studies have been completed. More PK studies are needed for: i) antiepileptics with potent inductive effects for all recently approved antidepressants; ii) high doses of mild CYP3A4 inducers, such as clobazam, eslicarbazepine, oxcarbazepine, rufinamide and topiramate for reboxetine and vilazodone; iii) valproate as a possible inhibitor, mild inducer or both a mild inducer and competitive inhibitor of some antidepressants; and iv) inhibitory effects of long-term fluoxetine use on clobazam, lacosamide, phenobarbital, primidone, carbamazepine, felbamate, tiagabine and zonisamide. Possible synergistic or additive beneficial PD DIs in generalized anxiety disorder, chronic pain, migraine prophylaxis, weight control and menopausal symptoms need study.

Original languageEnglish
Pages (from-to)1457-1489
Number of pages33
JournalExpert Opinion on Drug Metabolism and Toxicology
Volume10
Issue number11
DOIs
StatePublished - Nov 1 2014

Bibliographical note

Publisher Copyright:
© 2014 Informa UK, Ltd. All rights reserved.

Funding

Co., Janssen Pharmaceuticals, Lundbeck and Pfizer. J de Leon received researcher-initiated grants from Eli Lilly, Roche Molecular Systems, Inc. and in collaboration with Genomas, Inc., from the National Institutes of Health Small Business Innovation Research program. He has been on the advisory boards of Bristol-Myers Squibb and AstraZeneca. His lectures have been supported by Sandoz, Lundbeck, Pfizer, Eli Lilly, Janssen, Bristol-Myers Squibb and Roche Molecular Systems, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

FundersFunder number
National Institutes of Health Small Business Innovation Research program
Roche Molecular Systems, Inc.
Bristol-Myers Squibb
Eli Lilly and Company
Pfizer
Janssen Biotech
Sandoz
H. Lundbeck A/S

    Keywords

    • Antidepressants
    • Antiepileptics
    • Drug interactions
    • Pharmacodynamics
    • Pharmacokinetics

    ASJC Scopus subject areas

    • Toxicology
    • Pharmacology

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