APPENDIX E: Interactions for first-line and second-line antidepressants

First-Line Second-Line

Interactions 19 Bupropion Citalopram Desvenlafaxine Duloxetine Escitalopram Fluoxetine Fluvoxamine Mirtazapine Paroxetine, Immediate-Release Controlled- Paroxetine, Release Sertraline Venlafaxine Vortioxetine Levomilnacipran Moclobemide Quetiapine Trazodone Tricyclic antidepressants Vilazodone

All SSRIs inhibit certain cytochrome P450 isoenzymes and can reduce the clearance of many drugs (e.g. clozapine, methadone, mexiletine, phenytoin, pimozide, propafenone) or decrease the enzymatic conversion of a prodrug (e.g. clopidogrel, codeine, tamoxifen) to its active form. Inducers of cytochrome P450 isoenzymes (e.g. carbamazepine, phenobarbital, phenytoin, rifampin) may increase the clearance of SSRIs. △ △ △ △ △ △ △ Avoid combined use with drugs associated with prolonged QTc interval/ torsades de pointes (e.g. amiodarone, azithromycin, clarithromycin, domperidone, erythromycin, haloperidol, methadone, pimozide, quinine, sotalol, ziprasidone)

Use with MAOIs, linezolid or methylene blue may lead to a potentially fatal reaction, initially presenting with tremor, agitation, hypomania, △ △ △ △ △ △ △ △ △ △ △ △ △ △ △ △ △ hyperthermia and/or hypertension May increase levels of cyclophosphamide, ifosfamide and orphenadrine △ Increased risk of NSAIDs and antiplatelet agents △ △ △ △ △ △ △ Inhibitors of cytochrome P450 isoenzymes (e.g. cimetidine, clarithromycin, erythromycin, fluconazole, indinavir, isoniazid, △ △ △ △ △ △ △ itraconazole,ketoconazole, quinidine, ritonavir) may increase SSRI levels Potent inhibitors of CYP3A4 may increase serum drug concentrations △ △ △ Do not use with potent inhibitors of CYP1A2 such as ciprofloxacin, fluvoxamine, ketoconazole △ Sedative effects may be potentiated by alcohol or benzodiazepines △ QTc prolongation and torsades de pointes have occurred in patients at risk of QTc prolongation, patients taking concomitant medications that prolong △ QTc, or in cases of a drug overdose

Strong inhibitors of CYP2D6 or CYP3A4 (e.g. ketoconazole, quinidine, fluoxetine, paroxetine) may increase venlafaxine levels. △

Use caution if co-administering with drugs that affect serotonergic neurotransmitter systems (e.g. dextromethorphan, fentanyl, lithium, meperidine, methadone, pentazocine, SSRIs, St. John’s wort, tapentadol, △ △ tramadol, triptan, tryptophan)

Potential additive bleeding risk with drugs such as warfarin, ASA, other antiplatelet agents △

Avoid sympathomimetics, meperidine. Caution with opioids, antihypertensives, antipsychotics, SSRIs, selegiline, excessive tyramine, △ alcohol. Reduce dose with cimetidine

Additive sedation with CNS depressants. May potentiate antihypertensive drug effects. Inhibitors of CYP3A4 (e.g. clarithromycin, erythromycin, grapefruit juice, ketoconazole or prednisone) may increase quetiapine △ levels; Inducers of CYP3A4 (e.g. carbamazepine, phenytoin, rifampin) may reduce quetiapine levels

Toxicity may be increased by inhibitors of CYP3A4 (e.g. clarithromycin, erythromycin, grapefruit juice, ketoconazole). Effectiveness may be reduced by inducers of CYP3A4 (e.g. carbamazepine, phenytoin, △ rifampin). May potentiate effects of other CNS depressants and augment hypotensive effects of antihypertensives. Avoid use with MAOIs

Inducers of CYP1A2 (e.g. barbiturates, carbamazepine and rifampin) may decrease effect. Cimetidine and antipsychotics may increase effect and toxicity. Possible interaction with antiarrhythmics (may lead to increased △ effect of either drug). May reduce the antihypertensive effect of clonidine; may augment the hypotensive effect of thiazides

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