1A2 Tertiary amine tricyclic antidepressants (TCAs), dulox-Fluvoxamine, fluoxetine, moclobemide, Tobacco, omeprazole etine, theophylline, phenacetin, TCAs (demethylation), ramelteon clozapine, diazepam, caffeine 2C19 TCAs, citalopram (partly), warfarin, tolbutamide, Fluoxetine, fluvoxamine, sertraline, Rifampin phenytoin, diazepam imipramine, ketoconozole, omeprazole 2D6 TCAs, benztropine, perphenazine, clozapine, haloperidol, codeine/oxycodone, risperidone, class Ic antiarrhythmics, β blockers, trazodone, paroxetine, maprotiline, amoxapine, duloxetine, mirtazapine (partly), venlafaxine, bupropion 3A4 Citalopram, escitalopram, TCAs, glucocorticoids, androgens/estrogens, carbamazepine, erythromycin, Ca2+ channel blockers, levomilnacipran, protease inhibitors, sildenafil, alprazolam, triazolam, vincristine/ vinblastine, tamoxifen, zolpidem by concurrent administration of nefazodone such that a reduction in triazolam dosage by 75% is recommended. Likewise, administration of nefazodone with simvastatin has been associated with 20-fold increase in plasma levels of simvastatin.
Trazodone is a substrate but not a potent inhibitor of CYP3A4. As a result, combining trazodone with potent inhibitors of CYP3A4, such as ritonavir or ketoconazole, may lead to substantial increases in trazodone levels.
Vortioxetine is a substrate of CYP2D6 and 2B6, and it is recommended that the dose be cut in half when it is coadministered with fluoxetine or bupropion. Inducers of CYP isoenzymes such as rifampin, carbamazepine, and phenytoin will lower serum levels of vortioxetine and may require increasing the dose of vortioxetine.
D. Tetracyclic and Unicyclic Antidepressants
Bupropion is metabolized primarily by CYP2B6, and its metabolism may be altered by drugs such as cyclophosphamide, which is a substrate of 2B6. The major metabolite of bupropion, hydroxybupropion, is a moderate inhibitor of CYP2D6 and so can raise desipramine levels. Bupropion should be avoided in patients taking MAOIs.
Mirtazapine is a substrate for several CYP450 enzymes including 2D6, 3A4, and 1A2. Consequently, drugs that inhibit these isozymes may raise mirtazapine levels. However, mirtazapine is not an inhibitor of these enzymes. The sedating effects of mirtazapine may be additive with those of CNS depressants such as alcohol and benzodiazepines.
Amoxapine and maprotiline share most drug interactions common to the TCA group. Both are CYP2D6 substrates and should be used with caution in combination with inhibitors such as fluoxetine. Amoxapine and maprotiline also both have anticholinergic and antihistaminic properties that may be additive with drugs that share a similar profile.