OBJECT DRUGS

Antidepressants, Tricyclic:

• Amitriptyline (Elavil)
• Amoxapine (Asendin)
• Clomipramine (Anafranil)
• Desipramine (Norpramin)
• Doxepin (Sinequan, etc.)
• Imipramine (Tofranil, etc.)
• Nortriptyline (Aventyl, etc.)
• Protriptyline (Vivactil)
• Trimipramine (Surmontil)

PRECIPITANT DRUGS

Antidepressants, Other:

• Bupropion (Wellbutrin, etc.)
• Duloxetine (Cymbalta)
• Fluoxetine (Prozac, etc.)
• Fluvoxamine (Luvox, etc.)
• Nefazodone
• Paroxetine (Paxil, etc.)

Comment:

Antidepressants that inhibit CYP2D6 (and to a lesser extent inhibit CYP1A2 and CYP3A4) can increase tricyclic antidepressant (TCA) serum concentrations possibly leading to toxicity (e.g., dry mouth, urinary retention, blurred vision, tachycardia, constipation, and postural hypotension). With most inhibitors, the onset and offset of the interaction occurs over several days to a week, but it may take up to several weeks with fluoxetine. Combinations of TCAs and enzyme inhibitors (e.g., fluoxetine or paroxetine) are sometimes used intentionally to increase antidepressant efficacy.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative:
• Antidepressants, Other: Sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), desvenlafaxine (Pristiq), and venlafaxine (Effexor) have less effect on CYP2D6 than fluoxetine or paroxetine. Larger than usual doses of desvenlafaxine (eg, 400 mg/day) may produce moderate CYP2D6 inhibition, but little inhibition occurs at 100 mg/day.
• Monitor: Monitor for altered TCA response if an SSRI that is an enzyme inhibitor is initiated, discontinued, or changed in dosage.