New antidepressants and the cytochrome P450 system: Focus on venlafaxine, nefazodone, and mirtazapine

J. Randall Owen, Charles Nemeroff

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Objective: This review critically evaluates recent information on the cytochrome P450 system, with an emphasis on drug interactions involving antidepressant medications, particularly venlafaxine, nefazodone, and mirtazapine. Methods: International literature on the cytochrome P450 system and related drug interactions from 1995-1997 were critically examined. Results: Venlafaxine, nefazodone, and mirtazapine have different effects on the cytochrome P450 system. In vitro, venlafaxine is a weaker CYP2D6 inhibitor than most of the selective serotonin reuptake inhibitors (SSRIs) by a factor of 1-3 orders of magnitude. In vivo drug interaction studies generally confirm in vitro results. However, some exceptions exist. The clinical significance of such interactions remains unknown. Venlafaxine had minimal or no demonstrable inhibition of CYP1A2, CYP3A4, or CYP2C. Nefazodone is a potent inhibitor of CYP3A4 and is therefore absolutely contraindicated with concurrent administration of terfenadine, astemizole, and cisapride. It is a weak inhibitor of CYP1A2, 3A4, and 2D6. A metabolite of nefazodone, mCPP, is a weak and probably clinically insignificant inhibitor of CYP2D6. Mirtazapine was minimal inhibitory effects on CYP1A2, CYP3A4, and CYP2D6 in vitro. Little is known about its interactions with other drugs. Conclusions: With the addition of the latest antidepressant medications, the clinician may now choose antidepressants with little liability for drug-drug interactions. Venlafaxine and mirtazapine are associated with a lower risk of clinically significant drug interactions than SSRIs. Nefazodone is a potent inhibitor of CYP3A4 and therefore may not be suitable for all patient populations. It is, however, a much weaker CYP2D6 inhibitor than the SSRIs. More studies are needed to assess more accurately and precisely the risk of such untoward drug-drug interactions with these novel antidepressant, particularly in more diverse ethnic patient populations.

Original languageEnglish
Pages (from-to)24-32
Number of pages9
JournalDepression and Anxiety
Volume7
Issue numberSUPPL. 1
DOIs
StatePublished - May 30 1998
Externally publishedYes

Fingerprint

Drug Interactions
Cytochrome P-450 Enzyme System
Antidepressive Agents
Serotonin Uptake Inhibitors
Cytochrome P-450 CYP3A
Cytochrome P-450 CYP1A2
Astemizole
Pharmaceutical Preparations
Terfenadine
Cisapride
Cytochrome P-450 CYP2D6
Population
nefazodone
mirtazapine
Venlafaxine Hydrochloride
Cytochrome P-450 CYP2D6 Inhibitors
In Vitro Techniques

Keywords

  • Drug interactions
  • Mirtazapine
  • Nefazodone
  • P
  • Venlafaxine

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Psychology(all)
  • Clinical Psychology

Cite this

New antidepressants and the cytochrome P450 system : Focus on venlafaxine, nefazodone, and mirtazapine. / Owen, J. Randall; Nemeroff, Charles.

In: Depression and Anxiety, Vol. 7, No. SUPPL. 1, 30.05.1998, p. 24-32.

Research output: Contribution to journalArticle

@article{d1fe68c2dc9b4e66af9b15c9b20cd480,
title = "New antidepressants and the cytochrome P450 system: Focus on venlafaxine, nefazodone, and mirtazapine",
abstract = "Objective: This review critically evaluates recent information on the cytochrome P450 system, with an emphasis on drug interactions involving antidepressant medications, particularly venlafaxine, nefazodone, and mirtazapine. Methods: International literature on the cytochrome P450 system and related drug interactions from 1995-1997 were critically examined. Results: Venlafaxine, nefazodone, and mirtazapine have different effects on the cytochrome P450 system. In vitro, venlafaxine is a weaker CYP2D6 inhibitor than most of the selective serotonin reuptake inhibitors (SSRIs) by a factor of 1-3 orders of magnitude. In vivo drug interaction studies generally confirm in vitro results. However, some exceptions exist. The clinical significance of such interactions remains unknown. Venlafaxine had minimal or no demonstrable inhibition of CYP1A2, CYP3A4, or CYP2C. Nefazodone is a potent inhibitor of CYP3A4 and is therefore absolutely contraindicated with concurrent administration of terfenadine, astemizole, and cisapride. It is a weak inhibitor of CYP1A2, 3A4, and 2D6. A metabolite of nefazodone, mCPP, is a weak and probably clinically insignificant inhibitor of CYP2D6. Mirtazapine was minimal inhibitory effects on CYP1A2, CYP3A4, and CYP2D6 in vitro. Little is known about its interactions with other drugs. Conclusions: With the addition of the latest antidepressant medications, the clinician may now choose antidepressants with little liability for drug-drug interactions. Venlafaxine and mirtazapine are associated with a lower risk of clinically significant drug interactions than SSRIs. Nefazodone is a potent inhibitor of CYP3A4 and therefore may not be suitable for all patient populations. It is, however, a much weaker CYP2D6 inhibitor than the SSRIs. More studies are needed to assess more accurately and precisely the risk of such untoward drug-drug interactions with these novel antidepressant, particularly in more diverse ethnic patient populations.",
keywords = "Drug interactions, Mirtazapine, Nefazodone, P, Venlafaxine",
author = "Owen, {J. Randall} and Charles Nemeroff",
year = "1998",
month = "5",
day = "30",
doi = "10.1002/(SICI)1520-6394(1998)7:1+<24::AID-DA7>3.0.CO;2-F",
language = "English",
volume = "7",
pages = "24--32",
journal = "Depression and Anxiety",
issn = "1091-4269",
publisher = "Wiley-Blackwell",
number = "SUPPL. 1",

}

TY - JOUR

T1 - New antidepressants and the cytochrome P450 system

T2 - Focus on venlafaxine, nefazodone, and mirtazapine

AU - Owen, J. Randall

AU - Nemeroff, Charles

PY - 1998/5/30

Y1 - 1998/5/30

N2 - Objective: This review critically evaluates recent information on the cytochrome P450 system, with an emphasis on drug interactions involving antidepressant medications, particularly venlafaxine, nefazodone, and mirtazapine. Methods: International literature on the cytochrome P450 system and related drug interactions from 1995-1997 were critically examined. Results: Venlafaxine, nefazodone, and mirtazapine have different effects on the cytochrome P450 system. In vitro, venlafaxine is a weaker CYP2D6 inhibitor than most of the selective serotonin reuptake inhibitors (SSRIs) by a factor of 1-3 orders of magnitude. In vivo drug interaction studies generally confirm in vitro results. However, some exceptions exist. The clinical significance of such interactions remains unknown. Venlafaxine had minimal or no demonstrable inhibition of CYP1A2, CYP3A4, or CYP2C. Nefazodone is a potent inhibitor of CYP3A4 and is therefore absolutely contraindicated with concurrent administration of terfenadine, astemizole, and cisapride. It is a weak inhibitor of CYP1A2, 3A4, and 2D6. A metabolite of nefazodone, mCPP, is a weak and probably clinically insignificant inhibitor of CYP2D6. Mirtazapine was minimal inhibitory effects on CYP1A2, CYP3A4, and CYP2D6 in vitro. Little is known about its interactions with other drugs. Conclusions: With the addition of the latest antidepressant medications, the clinician may now choose antidepressants with little liability for drug-drug interactions. Venlafaxine and mirtazapine are associated with a lower risk of clinically significant drug interactions than SSRIs. Nefazodone is a potent inhibitor of CYP3A4 and therefore may not be suitable for all patient populations. It is, however, a much weaker CYP2D6 inhibitor than the SSRIs. More studies are needed to assess more accurately and precisely the risk of such untoward drug-drug interactions with these novel antidepressant, particularly in more diverse ethnic patient populations.

AB - Objective: This review critically evaluates recent information on the cytochrome P450 system, with an emphasis on drug interactions involving antidepressant medications, particularly venlafaxine, nefazodone, and mirtazapine. Methods: International literature on the cytochrome P450 system and related drug interactions from 1995-1997 were critically examined. Results: Venlafaxine, nefazodone, and mirtazapine have different effects on the cytochrome P450 system. In vitro, venlafaxine is a weaker CYP2D6 inhibitor than most of the selective serotonin reuptake inhibitors (SSRIs) by a factor of 1-3 orders of magnitude. In vivo drug interaction studies generally confirm in vitro results. However, some exceptions exist. The clinical significance of such interactions remains unknown. Venlafaxine had minimal or no demonstrable inhibition of CYP1A2, CYP3A4, or CYP2C. Nefazodone is a potent inhibitor of CYP3A4 and is therefore absolutely contraindicated with concurrent administration of terfenadine, astemizole, and cisapride. It is a weak inhibitor of CYP1A2, 3A4, and 2D6. A metabolite of nefazodone, mCPP, is a weak and probably clinically insignificant inhibitor of CYP2D6. Mirtazapine was minimal inhibitory effects on CYP1A2, CYP3A4, and CYP2D6 in vitro. Little is known about its interactions with other drugs. Conclusions: With the addition of the latest antidepressant medications, the clinician may now choose antidepressants with little liability for drug-drug interactions. Venlafaxine and mirtazapine are associated with a lower risk of clinically significant drug interactions than SSRIs. Nefazodone is a potent inhibitor of CYP3A4 and therefore may not be suitable for all patient populations. It is, however, a much weaker CYP2D6 inhibitor than the SSRIs. More studies are needed to assess more accurately and precisely the risk of such untoward drug-drug interactions with these novel antidepressant, particularly in more diverse ethnic patient populations.

KW - Drug interactions

KW - Mirtazapine

KW - Nefazodone

KW - P

KW - Venlafaxine

UR - http://www.scopus.com/inward/record.url?scp=0031959635&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031959635&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1520-6394(1998)7:1+<24::AID-DA7>3.0.CO;2-F

DO - 10.1002/(SICI)1520-6394(1998)7:1+<24::AID-DA7>3.0.CO;2-F

M3 - Article

C2 - 9597349

AN - SCOPUS:0031959635

VL - 7

SP - 24

EP - 32

JO - Depression and Anxiety

JF - Depression and Anxiety

SN - 1091-4269

IS - SUPPL. 1

ER -