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Gartlehner G, Hansen RA, Reichenpfader U, et al. Drug Class Review: Second-Generation Antidepressants: Final Update 5 Report [Internet]. Portland (OR): Oregon Health & Science University; 2011 Mar.

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

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Drug Class Review: Second-Generation Antidepressants: Final Update 5 Report [Internet].

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Appendix EPharmacokinetic properties and drug interactions

Second-generation antidepressant pharmacokinetic properties related to drug-drug interactions

Protein BindingSubstrate ofInhibits
Citalopram80%Major:CYP2C19; CYP3A4Weak:CYP1A2; CYP2B6; CYP2C19; CYP2D6
Minor:CYP2D6
Duloxetine> 90%Major:CYP1A2; CYP2D6Moderate:CYP2D6
Escitalopram56%Major:CYP2C19; CYP3A4Weak:CYP2D6
Fluoxetine94.5%Major:CYP2C8/9; CYP2D6Strong:CYP2D6
Minor:CYP1A2; CYP2B6; CYP2C19; CYP2E1; CYP3A4Moderate:CYP1A2
Weak:CYP2B6; CYP2C8/9; CYP3A4
Fluvoxamine80%Major:CYP1A2; CYP2D6Strong:CYP1A2; CYP2C19
Weak:CYP2B6; CYP3A4; CYP2D6; CYP2C8/9
Paroxetine95%Major:CYP2D6Strong:CYP2D6
Moderate:CYP2B6
Weak:CYP1A2; CYP2C19; CYP2C8/9; CYP3A4
Sertraline98%Major:CYP2C19; CYP2D6Moderate:CYP2C19; CYP2D6; CYP2B6; CYP3A4
Minor:CYP2B6; CYP3A4; CYP2C8/9Weak:CYP1A2; CYP2C8/9
Mirtazapine85%Major:CYP1A2; CYP2D6; CYP3A4Weak:CYP1A2; CYP3A4
Minor:CYP2C8/9
Venlafaxine27%Major:CYP2D6; CYP3A4Weak:CYP2B6; CYP2D6
Minor:CYP2C8/9; CYP2C19
Bupropion84%Major:CYP2C8/9Weak:CYP2D6
Minor:CYP1A2; CYP2A6; CYP2C8/9; CYP2D6 CYP2E1; CYP3A4
Nefazodone>99%Major:CYP2D6; CYP3A4Strong:CYP3A4
Weak:CYP1A2; CYP2B6; CYP2D6
Desvenlafaxine30%Minor:CYP3A4Weak:CYP3A4
*

Pharmacokinetic properties abstracted from Lexi-Comp online (licensed by the University)

Clinically Significant Drug Interactions: SSRIs

Interacting DrugCitalopramEscitalopramFluoxetine
CarbamazepineMonitor (1)aMonitor (2)aMonitor (3)d
CimetidineMonitor (1)bMonitor (2)b
ClozapineMonitor (3)d
DiazepamMonitor (3)d
DigoxinNo significant interaction (1)No significant interaction (2)Monitor (3)d
HaloperidolMonitor (3)d
KetoconazoleMonitor (1)cMonitor (2)c
LithiumMonitor (1)Monitor (2)bMonitor (3)
MAOIsContraindicatedContraindicatedContraindicated
MetoprololMonitor (1)dMonitor (2)d
PhenytoinMonitor (3)d
PimozideMonitor (3)d
SumatriptanMonitor (1)Monitor (2)Monitor (3)
RitonavirNo significant interaction (2)
TCAsMonitor (1)d
TheophyllineNo significant interaction (1)No significant interaction (2)
ThioridazineContraindicated
TriazolamNo significant interaction (1)No significant interaction (2)
TryptophanMonitor (3)
WarfarinMonitor (1)Monitor (2)Monitor (3)d
WarfarinMonitor (1)Monitor (2)Monitor (3)d
a

Decrease in second-generation antidepressant plasma levels

b

Increase in second-generation antidepressant plasma levels

c

Decrease in plasma levels for the interacting drug or its active metabolite

d

Increase in plasma levels for the interacting drug or its active metabolite

(1)

Citalopram package insert

(2)

Escitalopram package insert

(3)

Fluoxetine package insert

Clinically Significant Drug Interactions: SSRIs

Interacting DrugFluvoxamineParoxetineSertraline
AlprazolamMonitor (4)d
AtenololNo significant interaction (6)
CimetidineMonitor (5)bMonitor (6)b
DiazepamMonitor (4)dMonitor (5)Monitor (6)
DigoxinMonitor (5)cMonitor (6)d
LithiumMonitor (5)Monitor (6)
LorazepamNo significant interaction (4)
MAOIsContraindicated (4)Contraindicated (5)Contraindicated (6)
PhenobarbitalMonitor (5)
PhenytoinMonitor (5)
PimozideContraindicated (4)Contraindicated (6)
ProcyclidineMonitor (5)d
PropranololNo significant interaction (5)
TriptansMonitor (5)Monitor (6)
TCAsMonitor (5)Monitor (6)
TemazepamNo significant interaction (4)
TheophyllineMonitor (4)dMonitor (5)d
ThioridazineContraindicatedContraindicated (5)
TolbutamideMonitor (6)d
TramadolMonitor (5)d
TriazolamMonitor (4)d
TryptophanMonitor (5)
WarfarinMonitor (4)dMonitor (5)dMonitor (6)d
a

Decrease in second-generation antidepressant plasma levels

b

Increase in second-generation antidepressant plasma levels

c

Decrease in plasma levels for the interacting drug or its active metabolite

d

Increase in plasma levels for the interacting drug or its active metabolite

(4)

Fluvoxamine package insert

(5)

Paroxetine package insert

(6)

Sertraline package insert

Clinically Significant Drug Interactions: Mirtazapine, Venlafaxine

Interacting DrugMirtazapineVenlafaxine
AlprazolamMonitor (7)
AmiodaroneMonitor (7)b
CarbamazepineMonitor (7)a
CimetidineMonitor (8)d
CiprofloxacinMonitor (7)b
DiazepamMonitor (7)No significant interaction (8)
ErythromycinMonitor (7)b
HaloperidolMonitor (8)d
IndinavirMonitor (8)c
KetoconazoleMonitor (7)b
LithiumNo significant interaction (8)
LorazepamMonitor (7)
MAOIsContraindicated (7)Contraindicated (8)
PhenobarbitalMonitor (7)a
PhenytoinMonitor (7)a
RisperidoneMonitor (8)d
TCAsMonitor (8)d
TemazepamMonitor (7)
TriazolamMonitor (7)
a

Decrease in second-generation antidepressant plasma levels

b

Increase in second-generation antidepressant plasma levels

c

Decrease in plasma levels for the interacting drug or its active metabolite

d

Increase in plasma levels for the interacting drug or its active metabolite

(7)

Mirtazapine package insert

(8)

Venlafaxine package insert

Clinically Significant Drug Interactions: Bupropion, Nefazodone

Interacting DrugBuproprionNefazodone
AlprazolamMonitor (10)d
AmantadineMonitor (9)
AtenololMonitor (9)
BuspironeMonitor (10)
CarbamazepineMonitor (9)Contraindicated (10)
CimetidineMonitor (9)bNo significant interaction (10)
CyclosporineMonitor (10)d
DigoxinMonitor (10)
FlecainideMonitor (9)
HaloperidolMonitor (9)Monitor (10)d
HMG-CoA Reductase InhibitorsMonitor (10)d
KetoconazoleMonitor (9)
LevodopaMonitor (9)
LithiumMonitor (10)
LorazepamNo significant interaction (10)
MAOIsContraindicated (9)Contraindicated (10)
MetoprololMonitor (9)
PhenobarbitalMonitor (9)
PhenytoinMonitor (9)Monitor (10)
PimozideContraindicated (10)
PropafenoneMonitor (9)
PropranololMonitor (9)Monitor (10)b
RisperidoneMonitor (9)
TacrolimusMonitor (10)d
TCAsMonitor (9)Monitor (10)
TheophyllineMonitor (9)Monitor (10)
ThioridazineMonitor (9)
TriazolamContraindicated (10)
a

Decrease in second-generation antidepressant plasma levels

b

Increase in second-generation antidepressant plasma levels

c

Decrease in plasma levels for the interacting drug or its active metabolite

d

Increase in plasma levels for the interacting drug or its active metabolite

(9)

Buproprion package insert

(10)

Nefazodone package insert

Clinically Significant Drug Interactions: Mirtazapine, Venlafaxine

Interacting DrugDuloxetineDesvenlafaxine
AspirinMonitor (11)dMonitor (12)d
CimetidineMonitor (11)b
CiprofloxacinMonitor (11)b
DesipramineMonitor (11)dMonitor (12)d
EnoxacinMonitor (11)b
KetoconazoleMonitor (12)b
LithiumNot recommended (11)
LorazepamNo significant interaction (11)
MAOIsContraindicated (11)Contraindicated (12)
MidazolamMonitor (12)c
NSAIDSMonitor (11)dMonitor (12)d
QuinidineMonitor (11)b
TemazepamNo significant interaction (11)
TriptansMonitor (11)b
WarfarinMonitor (11)dMonitor (12)d
a

Decrease in second-generation antidepressant plasma levels

b

Increase in second-generation antidepressant plasma levels

c

Decrease in plasma levels for the interacting drug or its active metabolite

d

Increase in plasma levels for the interacting drug or its active metabolite

(11)

Duloxetine package insert

(12)

Desvenlafaxine package insert

Copyright © 2011 Oregon Health & Science University.
Bookshelf ID: NBK54353

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