OBJECT DRUGS

Opioid Analgesics (Serotonergic):

• Alfentanil (Alfenta)
• Fentanyl (Sublimaze, etc.)
• Meperidine (Demerol)
• Methadone (Dolophine, etc.)
• Tapentadol (Nucynta, etc.)
• Tramadol (Ultram, etc.)

PRECIPITANT DRUGS

SSRI and SNRI:

• Citalopram (Celexa)
• Clomipramine (Anafranil)
• Desvenlafaxine (Pristiq, etc.)
• Duloxetine (Cymbalta)
• Escitalopram (Lexapro)
• Fluoxetine (Prozac, etc.)
• Fluvoxamine (Luvox, etc.)
• Levomilnacipran (Fetzima)
• Imipramine (Tofranil, etc.)
• Milnacipran (Savella)
• Paroxetine (Paxil, etc.)
• Sertraline (Zoloft)
• Venlafaxine (Effexor)
• Vilazodone (Viibryd)
• Vortioxetine (Brintellix)

Comment:

There have been a number of cases of serotonin syndrome following the combined use of serotonergic analgesics such as meperidine or tramadol with selective serotonin reuptake inhibitors (SSRI) or selective serotonin-norepinephrine reuptake inhibitors (SNRI). One case of fatal serotonin syndrome was reported in a patient on amitriptyline following the addition of tramadol. Limited evidence suggests that fentanyl may also exhibit additive serotonergic effects with other serotonergic drugs, but more evidence is needed. Use particular care if the SSRI or SNRI is also an inhibitor of the metabolism of the opioid.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative:
• Opioid Analgesic: In patients taking an SSRI or SNRI consider using an alternative to the serotonergic opioid.
• Antidepressant: If a tricyclic antidepressant (TCA) is given to patients on a serotonergic opioid, use a TCA other than clomipramine or imipramine. Avoiding amitriptyline, doxepin and desipramine would also be prudent.
• Monitor: Monitor for evidence of excessive and/or prolonged opioid effects, including sedation and respiratory depression.