Duloxetine: A Balanced and Selective Norepinephrine and Serotonin-Reuptake Inhibitor

Anders D. Westanmo; Jon Gayken; Robert Haight


Am J Health Syst Pharm. 2005;62(23):2481-2490. 

In This Article

Drug Interactions

Some antidepressants that inhibit CYP2D6 include, in order of decreasing potency, paroxetine, nor-fluoxetine, fluoxetine, duloxetine, sertraline, citalopram, and fluvoxamine.[34,75–77] Duloxetine has been shown to be both a substrate and a moderate inhibitor of CYP2D6.[34,75] However, some clinicians state that dosage adjustments of duloxetine are probably not necessary when it is combined with CYP2D6 inhibitors or substrates.[76]

In patients receiving serotonergic medications in combination with an MAOI, there have been reports of serious and sometimes fatal reactions, including hyperthermia, rigidity, myoclonus, autonomic instability, and mental status changes that may progress to delirium and coma. The combined effects of duloxetine and MAOIs have not been evaluated in humans to date. It is recommended that duloxetine not be used in combination with an MAOI or within 14 days of discontinuing treatment with an MAOI. Conversely, an MAOI should not be initiated for at least five days after discontinuation of duloxetine.[25]

Duloxetine is highly protein bound (>90%) in human plasma.[25] Interactions between duloxetine and other highly protein-bound medications have not been evaluated to date. Therefore, adding or removing duloxetine to existing medication regimens should be attempted cautiously if an effect on protein binding is a clinical concern.[25]