Trazodone Interaction Library
How trazodone interacts with other prescription medications, over-the-counter drugs, supplements, alcohol, and cannabis — each rated by how well-established the evidence is.
Trazodone and 5-HTP
5-HTP is even closer to active serotonin than tryptophan in the body's production pathway, carrying a similar or greater serotonin syndrome…
Read more → Per FDA labelTrazodone and alcohol
Alcohol significantly compounds trazodone's sedative and blood-pressure-lowering effects, and this combination is specifically discouraged i…
Read more → Limited evidenceTrazodone and aspirin
Like other NSAIDs, aspirin's antiplatelet effect combined with trazodone's serotonergic activity can modestly add to bleeding risk.
Read more → Per FDA labelTrazodone and azole antifungals
Strong CYP3A4 inhibitors like ketoconazole and itraconazole can substantially raise trazodone blood levels, increasing the risk of side effe…
Read more → Well establishedTrazodone and benzodiazepines
Both drug classes are CNS depressants, and combining them significantly increases sedation, coordination problems, and fall risk.
Read more → Limited evidenceTrazodone and bupropion
Bupropion works on dopamine and norepinephrine rather than serotonin, but the combination with trazodone is common in practice and worth und…
Read more → Limited evidenceTrazodone and buspirone
Buspirone, an anti-anxiety medication with serotonergic activity, is sometimes combined with trazodone but adds to overall serotonergic load…
Read more → Limited evidenceTrazodone and cannabis
Cannabis can add to trazodone's sedating effects and, in some people, affect heart rate and blood pressure in ways that compound trazodone's…
Read more → Well establishedTrazodone and carbamazepine
Carbamazepine strongly induces the CYP3A4 enzyme that breaks down trazodone, which can significantly lower trazodone blood levels and reduce…
Read more → Limited evidenceTrazodone and clopidogrel (or other antiplatelet medications)
Prescription antiplatelet medications carry a more significant baseline bleeding-risk profile, making the additive effect of a serotonergic…
Read more → Limited evidenceTrazodone and dextromethorphan (DXM)
Dextromethorphan, found in many over-the-counter cough and cold products, has serotonergic activity that can add to trazodone's effects.
Read more → Well establishedTrazodone and digoxin
Case reports and pharmacology literature describe trazodone increasing digoxin blood levels, which matters because digoxin has a narrow safe…
Read more → Well establishedTrazodone and diphenhydramine (Benadryl and similar OTC sleep aids)
Diphenhydramine works partly through the same antihistamine mechanism as trazodone's sedating effect, and combining them can cause excessive…
Read more → Limited evidenceTrazodone and general anesthesia (surgery)
Trazodone's sedative and cardiovascular effects are relevant to anesthesia planning, so surgical and anesthesia teams should always be told…
Read more → Limited evidenceTrazodone and grapefruit juice
Grapefruit is a well-known CYP3A4 inhibitor for many medications, and some data suggests it can raise trazodone levels similarly to prescrip…
Read more → Per FDA labelTrazodone and linezolid
Linezolid is an antibiotic with MAOI-like activity, and combining it with serotonergic antidepressants including trazodone carries a labeled…
Read more → Limited evidenceTrazodone and lithium
Lithium can enhance serotonergic effects and has been reported in combination with trazodone to occasionally contribute to serotonin-related…
Read more → Well establishedTrazodone and macrolide antibiotics
Clarithromycin and erythromycin are CYP3A4 inhibitors that can raise trazodone levels similarly to azole antifungals.
Read more → Per FDA labelTrazodone and MAOIs (monoamine oxidase inhibitors)
Combining trazodone with an MAOI carries a serious, well-documented serotonin syndrome risk. A washout period of roughly 14 days is generall…
Read more → Limited evidenceTrazodone and melatonin
Melatonin is a mild sedative supplement, and while it does not share trazodone's serotonergic mechanism, its sedative effect can still add t…
Read more → Per FDA labelTrazodone and methylene blue
Methylene blue, used in certain medical procedures and to treat methemoglobinemia, also has MAOI-like activity and carries the same serotoni…
Read more → Limited evidenceTrazodone and mirtazapine
Both trazodone and mirtazapine are sedating antidepressants with serotonergic activity; combining them adds both sedation and serotonin synd…
Read more → Limited evidenceTrazodone and NSAIDs
Combining a serotonergic medication with NSAIDs may modestly increase bleeding risk, particularly gastrointestinal bleeding, compared with e…
Read more → Well establishedTrazodone and opioid pain medications
Opioids and trazodone both depress the central nervous system, and combined use raises the risk of excessive sedation and slowed breathing.
Read more →Not sure if your combination is covered here?
The Interaction Question Builder walks through your specific medications and generates a printable summary of questions to bring to your pharmacist or prescriber.