Summary Brief Abstract Citation ASN.1 MEDLINE XML UI List LinkOut Related Articles Cited in Books Domain Links 3D Domain Links GEO DataSet Links Gene Links Genome Links GEO Links Nucleotide Links OMIM Links PMC Links Cited in PMC PopSet Links Protein Links SNP Links Structure Links UniSTS Links  Show: 5 10 20 50 100 200 500 Sort Author Journal Pub Date Text File Clipboard E-mail Order

1: Curr Drug Metab. 2002 Feb;3(1):13-37.

Related Articles, Links

Selective serotonin reuptake inhibitors and cytochrome P-450 mediated drug-drug interactions: an update.

Hemeryck A, Belpaire FM.

Heymans Institute of Pharmacology, Ghent University, Faculty of Medicine and Health Sciences, Belgium. ahemeryc@janbe.jnj.com

The selective serotonin reuptake inhibitors (SSRIs) have become the most prescribed antidepressants in many countries. Although the SSRIs share a common mechanism of action, they differ substantially in their chemical structure, metabolism, and pharmacokinetics. Perhaps the most important difference between the SSRIs is their potential to cause drug-drug interactions through inhibition of cytochrome-P450 (CYP) isoforms. This paper provides an update on both the in vitro and in vivo evidence with respect to CYP-mediated drug-drug interactions with this class of antidepressants. The available evidence clearly indicates that the individual SSRIs display a distinct profile of cytochrome P450 inhibition. Fluvoxamine is a potent CYP1A2 and CYP2C19 inhibitor, and a moderate CYP2C9, CYP2D6, and CYP3A4 inhibitor. Fluoxetine and paroxetine are potent CYP2D6 inhibitors, whereas fluoxetine's main metabolite, norfluoxetine, has a moderate inhibitory effect on CYP3A4. Sertraline is a moderate CYP2D6 inhibitor; citalopram appears to have little effect on the major CYP isoforms. Fluoxetine deserves special attention as inhibitory effects on CYP-activity can persist for several weeks after fluoxetine discontinuation because of the long half-life of fluoxetine and its metabolite norfluoxetine. Drug combinations with SSRIs should be assessed on an individual basis. Knowledge regarding the CYP-isoforms involved in the metabolism of the co-administered drug may help clinicians to anticipate and avoid potentially dangerous drug-drug interactions. Anticipated interactions can usually be managed by appropriate dose adjustment and titration of the object drug. In some cases, therapeutic drug monitoring can be useful. Equally well, an SSRI with limited interaction potential may be selected to treat depression in patients that receive other medications.

Publication Types:

• Review
• Review, Academic

PMID: 11876575 [PubMed - indexed for MEDLINE]

Jan 29 2004 15:06:34