Trazodone Interactions: Antidepressants, Sleep Aids and Other Medicines
Trazodone is often taken alongside an antidepressant or other sleep medicines. Some combinations add to drowsiness or raise the risk of serotonin syndrome.
By withClaro Editorial · 2026-11-02 · 4 min read
Clinical section reviewed by Dr. Jason Tan , Consultant Psychiatrist, on October 27, 2026.
Key takeaways Never combine trazodone with an MAOI, including linezolid or IV methylene blue, or within 14 days of one. Trazodone lengthens the QT interval, so the label says to avoid other drugs that do the same, including some antipsychotics, and strong CYP3A4 inhibitors. With other serotonin medicines, such as SSRIs, triptans, tramadol or buspirone, the risk of serotonin syndrome rises; with other sleep aids, drowsiness adds up. On Reddit, mostly in insomnia threads, other antidepressants, benzodiazepines and antipsychotics came up most alongside trazodone. On this page
Which medicines interact with trazodone? What 56 people on Reddit said they take with trazodone What about trazodone with an SSRI? What should you tell your prescriber about other medicines? Trazodone interacts with other medicines in three main ways. It adds to drowsiness from alcohol and other sedatives, it can raise serotonin syndrome risk with other serotonin medicines, and some drugs change its levels in the blood. It must not be combined with MAOI antidepressants.
Which medicines interact with trazodone?
MAOIs are ruled out completely. The label says to avoid drugs that lengthen the QT interval and strong CYP3A4 inhibitors, to watch for serotonin syndrome with other serotonin medicines, and warns that drowsiness adds up with alcohol and sedatives.
The heart warning matters most. Trazodone lengthens the QT interval, and the label lists this among its warnings and says to avoid it in people with heart rhythm problems. It links arrhythmias mainly to existing heart disease, and also notes rare reports, collected after approval, of torsade de pointes, a dangerous heart rhythm, at doses of 100 mg or less of the immediate-release form. If you take an antipsychotic, an antiarrhythmic or an antibiotic as well, tell your prescriber or pharmacist before starting. Fainting or a pounding, irregular heartbeat on trazodone needs a call the same day.
The groups in full:
Group Examples What the label says MAOIs phenelzine, tranylcypromine, selegiline, isocarboxazid, linezolid, IV methylene blue do not combine, and keep 14 days apart either way Drugs that lengthen QT some antipsychotics such as ziprasidone, chlorpromazine, thioridazine; quinidine, amiodarone, sotalol; some antibiotics avoid together Strong CYP3A4 inhibitors itraconazole, clarithromycin, voriconazole avoid together, or consider a lower trazodone dose; decided with your prescriber Strong CYP3A4 inducers carbamazepine may lower trazodone levels Serotonin medicines SSRIs, triptans, tricyclics, fentanyl, lithium, tramadol, buspirone, St. John's wort higher risk of serotonin syndrome Blood thinners and NSAIDs warfarin, aspirin, ibuprofen more bleeding risk; check clotting on warfarin Digoxin and phenytoin digoxin (heart), phenytoin (seizures) levels may rise; monitor them Alcohol and sedatives sleeping pills, benzodiazepines more drowsiness
What 56 people on Reddit said they take with trazodone
We read 100 recent threads about taking trazodone with other medicines, comments included, and 56 people described their own combination. The threads came mostly from r/insomnia, so these are mainly people taking trazodone for sleep, and people who found a combination that works are more likely to share it, so treat this as a range of experiences. Another antidepressant was what they most often took with trazodone, named by 16 of the 56; one person could name several:
Taken with trazodone Of 56 people Another antidepressant 16 Benzodiazepine 7 Antipsychotic 6 Bupropion 5 ADHD stimulant 5 Hydroxyzine 4
Another 23 named other medicines. Of the 56, 21 said how the combination went: 13 better, 4 mixed, 3 worse or stopped, and 1 no difference. One person on r/insomnia wrote:
Works wonders for me, i'm able to fall asleep and stay asleep
For another it was mixed:
It works but I do wake up often and groggy.
What about trazodone with an SSRI? Medically reviewed by Dr. Jason Tan on October 27, 2026, this section only.
It is a pairing people report: in our count, another antidepressant was the most common medicine taken with trazodone. Both act on serotonin, so the label asks for watching for serotonin syndrome, especially when a medicine is started or a dose goes up, and this is usually done under a prescriber's eye. The clinical view:
Serotonin syndrome usually appears within hours of starting a medication or raising a dose. Mild signs include restlessness, sweating, shivering, diarrhea, a fast heartbeat and twitching muscles. High fever, rigid muscles, confusion or seizures need emergency care.
Tell your prescriber and pharmacist about everything you take, including supplements. Starting or stopping one of them can change how the others work. ## Can you take trazodone with other sleep aids?
Usually not without your prescriber's plan, because the effects stack. The label says trazodone may strengthen the effects of alcohol, barbiturates and other medicines that slow the brain. Prescription sleeping pills and benzodiazepines are among these, and sedating antihistamines such as diphenhydramine or hydroxyzine also cause drowsiness, so it can add up with them too. Melatonin also aims at sleep, so its effect can stack with trazodone's drowsiness, even though the label doesn't name it. Whatever you add, start nothing new on the same night without checking, and tell your prescriber if you feel unusually groggy, dizzy or unsteady the next morning.
What should you tell your prescriber about other medicines?
Over-the-counter sleep aids and supplements count too, so bring a full list. It helps to tell them:
All prescription medicines, with doses. Sleep aids, antihistamines and melatonin. Migraine and pain medicines. Alcohol, cannabis and other substances. Any heart rhythm problems. More on side effects in trazodone side effects .
Download on the App Store When two medicines change together, it is hard to tell which one is doing what. The withClaro app lets you log sleep, mood and side effects each day, linked to your doses, and turns it into a report for your prescriber.
Frequently asked questions Can you take trazodone with Wellbutrin? The trazodone label doesn't name bupropion, and 5 people in our count took both. Bupropion doesn't act mainly on serotonin, so the concern is less serotonin syndrome than how the two feel together; ask your prescriber before adding one to the other.
Can you take trazodone with melatonin? Both make you sleepy, so the drowsiness can add up. Ask your pharmacist about the doses and note how you feel the next morning.
Can you take trazodone with Xanax? Both cause drowsiness. Don't combine them unless your prescriber has planned it.
Is trazodone an MAOI? No, but it must not be taken with an MAOI or within 14 days of one.
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Sources TRAZODONE HYDROCHLORIDE tablets prescribing information, US Food and Drug Administration via DailyMed Claro articles are for self-monitoring and educational purposes only. They are not a medical device, therapist, or diagnostic tool, and do not replace care from your prescribing clinician. If you are in crisis, contact your care team, emergency services, the Samaritans (UK: 116 123), or the Crisis Text Line (US: text HOME to 741741).