11 Trazodone Interactions You Should Know About

GoodRx Health

You may have heard of trazodone as a medication to treat insomnia (difficulty sleeping). But you might be surprised to hear that it's not FDA approved for insomnia. This is what's called an off-label use. While trazodone is FDA approved to treat depression, it isn't often used for this reason. Other medications, like selective serotonin reuptake inhibitors (SSRIs), are considered first-choice medication options.

Although trazodone can be an effective option for insomnia, it also has many possible drug interactions. Trazodone can interact with medications that share similar side effects. It can also interact with medications that affect how it's metabolized (broken down) in the body. Examples include SSRIs like Lexapro (escitalopram), benzodiazepines such as Xanax (alprazolam), and opioid pain medications like hydrocodone (Hysingla extended-release). Trazodone and alcohol can also interact.

Here, we'll cover 11 trazodone interactions to know about and how to prevent or manage them.

1. Alcohol

Alcohol can have many effects on the body, including changes in mood, abnormal heartbeat, and drowsiness. Experts believe there's no amount of alcohol that's considered absolutely safe to drink. And combining alcohol and trazodone can be even more risky.

Trazodone can cause drowsiness and dizziness, which can be worsened by alcohol. Heart issues can also occur. This is why it's best to avoid drinking alcohol while you're taking trazodone. If you're unable to eliminate alcohol while taking trazodone, let your prescriber know.

2. Medications that increase serotonin, such as Lexapro, Prozac, and Cymbalta

One way trazodone works is by raising serotonin levels in the brain. Serotonin is a chemical that's important for many bodily functions. This includes regulating your mood, controlling bowel movements, and helping you sleep.

But when there's too much serotonin in the brain, serotonin syndrome can occur. Mild symptoms include tremors, sweating, and a fast heartbeat. Severe symptoms include agitation, high fever, and uncontrollable movements. In some cases, serotonin syndrome is life-threatening.

Serotonin syndrome rarely occurs with trazodone alone. If it happens, it's usually caused by taking multiple medications that increase serotonin levels or taking high doses of these medications. Here are a few examples of medications and supplements that raise serotonin levels:

• SSRIs, such as Lexapro, Zoloft (sertraline), and Prozac (fluoxetine)

• Serotonin and norepinephrine reuptake inhibitors (SNRIs), such as Cymbalta (duloxetine)

• Tricyclic antidepressants (TCAs), such as amitriptyline

• Monoamine oxidase inhibitors (MAOIs), such as selegiline (Zelapar, Emsam)

• Opioids, such as hydrocodone / acetaminophen and tramadol (Conzip, Qdolo)

• Triptans, such as sumatriptan (Imitrex)

• St. John's wort

• Buspirone (commonly known as Buspar, though the brand name has been discontinued)

Combining trazodone with SSRIs or SNRIs could also increase the risk of bleeding. So before starting trazodone, give your healthcare team an updated list of prescription and over-the-counter (OTC) medications you take. They can check for trazodone interactions. And let them know if you've taken an MAOI medication within the past 2 weeks, as trazodone isn't recommended in this case.

3. Blood thinners and antiplatelet medications, such as Xarelto, warfarin, and Plavix

Medications that help prevent blood clots can raise your risk of bleeding. This includes antiplatelet and anticoagulant medications. These medications are sometimes referred to as "blood thinners."

Trazodone can also increase your risk of bleeding. So combining trazodone with blood thinners may make bleeding even more likely. Examples of blood thinners that can interact with trazodone include:

• Warfarin (Jantoven)

• Rivaroxaban (Xarelto)

• Apixaban (Eliquis)

• Dabigatran (Pradaxa)

• Clopidogrel (Plavix)

If you're taking a blood thinner, your prescriber may recommend another medication besides trazodone that has less of a bleeding risk. Or they may just recommend watching for symptoms of bleeding, such as unusual nose bleeds, unexplained bruising, and blood in your stool or urine. And if you're taking warfarin, you may have more frequent blood tests while you're taking trazodone. This will help your healthcare team decide if your warfarin dose needs to be adjusted.

4. Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen

Nonsteroidal anti-inflammatory drugs (NSAIDs) are medications that treat pain, fever, and inflammation. Some NSAIDs are available OTC, and include ibuprofen (Advil, Motrin) and naproxen (Aleve). Like trazodone, these medications can increase your risk of bleeding. This makes them risky to take together.

Still, talk with your prescriber if you're considering taking an NSAID like ibuprofen with trazodone.

So, what pain reliever can you take with trazodone? Your prescriber may recommend a different one, such as Tylenol (acetaminophen). Tylenol doesn't increase your risk of bleeding, and trazodone and Tylenol aren't known to interact.

5. Medications that increase trazodone levels, such as fluconazole

Some medications affect how trazodone is metabolized. They may block liver proteins (enzymes) that are responsible for breaking down trazodone in the body. When these enzymes are blocked, trazodone lasts longer in the body. This can lead to worsening side effects, such as drowsiness and dry mouth. Examples of these medications include:

• Antifungals, such as ketoconazole, itraconazole (Sporanox), and fluconazole (Diflucan)

• Clarithromycin

• Verapamil

This isn't a complete list of medications that can increase trazodone levels. So ask your prescriber and pharmacist to review your current medication list. Your prescriber may lower your trazodone dose if necessary. Or they may recommend an alternative to trazodone. Alternatively, they may simply ask you to watch for worsening trazodone side effects.

6. Medications that decrease trazodone levels, such as carbamazepine

Other medications can make the enzymes that break down trazodone more active. This may decrease trazodone levels, making it less effective. Examples of these medications include:

• Rifampin (Rifadin)

• Seizure medications, such as carbamazepine (Tegretol, Tegretol XR) and phenytoin (Dilantin, Phenytek)

• St. John's wort

This isn't a complete list of medications that can decrease trazodone levels. Ask your prescriber and pharmacist to review your current medication list. Your prescriber may adjust your medication dosages or recommend another medication besides trazodone. Or they may simply ask you to watch for signs that trazodone isn't working as well.

7. Medications that affect your heart rhythm, such as Seroquel

Trazodone can cause changes to your heart rhythm. This can cause abnormal heartbeats (arrhythmias). The risk is greater when trazodone is taken with other medications that can also affect your heart rhythm. Examples of these medications include:

• Amiodarone (Pacerone)

• Sotalol (Betapace)

• Hydroxyzine (Vistaril)

• Chlorpromazine

• Ziprasidone (Geodon)

• Seroquel (quetiapine)

You may need to avoid combining trazodone with medications that can cause arrhythmias. And if you have a history of arrhythmias, slowed heartbeat, low potassium, or low magnesium levels, trazodone may not be the best option for you. Additionally, your prescriber may want you to avoid trazodone if you have a medical condition known as long QT syndrome. This is a heart condition that can lead to arrhythmias.

8. Benzodiazepines, such as Xanax

Benzodiazepines are part of a group of medications known as sedatives. Sedatives slow down your brain activity. While trazodone isn't a benzodiazepine or sedative, it has sedative-like effects. This is why trazodone is sometimes prescribed off-label to treat insomnia.

If you combine trazodone with benzodiazepines or other sedative medications, it can be dangerous. It can lead to:

• Forgetfulness

• Trouble with coordination

• Confusion

• Excessive sleepiness

• Slowed breathing, leading to overdose

If you take benzodiazepines regularly, your prescriber may suggest an alternative to trazodone.

9. Sleep medications, such as Ambien

Other medications used for sleep, including Ambien (zolpidem), shouldn't be combined with trazodone. They can result in excessive drowsiness and slowed breathing. Other examples of sleep medications include:

• Lunesta (eszopiclone)

• Benadryl, ZzzQuil, Unisom SleepGels (diphenhydramine)

• Ramelteon (Rozerem)

• Doxepin (Silenor)

• Belsomra (suvorexant)

• Dayvigo (lemborexant)

If you take any medications for sleep, let your prescriber know. They may recommend avoiding trazodone to prevent too much drowsiness.

Can you take melatonin with trazodone for sleep?

Taking trazodone and melatonin together can cause excessive drowsiness.

Even though melatonin is available OTC, check with your prescriber or pharmacist before taking it if you're taking trazodone. They may recommend avoiding the combination.

10. Other medications that cause dizziness or drowsiness, such as hydrocodone and gabapentin

Even medications that aren't used specifically for sleep can cause drowsiness or dizziness. Several examples include:

• Barbiturates, such as phenobarbital

• Opioids, such as hydrocodone (Hysingla extended-release)

• Antipsychotics, such as Seroquel

• Muscle relaxers, such as cyclobenzaprine (Amrix)

• Hydroxyzine

• Buspirone

• Blood pressure medications, such as lisinopril (Zestril) or metoprolol (Lopressor, Toprol XL)

• Gabapentinoids, such as gabapentin (Neurontin) and pregabalin (Lyrica)

Combining these medications with trazodone can result in excessive drowsiness, confusion, or dizziness. More seriously, it can lead to slowed breathing and overdose in some cases. These effects are more likely if you're taking high doses of these medications as well.

Your healthcare team can help ensure you avoid these potential interactions by reviewing your medication list.

11. Narrow therapeutic index medications, such as digoxin and phenytoin

Digoxin (Lanoxin) is a medication that can help control heart rate and symptoms of heart failure. Phenytoin is an anti-seizure medication. Both digoxin and phenytoin are what's known as "narrow therapeutic index" medications. This means the difference between effective doses and toxic doses is very small.

Trazodone may raise the levels of digoxin and phenytoin in the body. This can cause toxicity quickly. Common signs of digoxin toxicity include nausea, vomiting, and diarrhea. More seriously, it can lead to life-threatening heart problems. Common signs of phenytoin toxicity include confusion, dizziness, and, more seriously, a coma. If you experience any of these symptoms, contact your prescriber immediately. You may also need to seek emergency help if symptoms are severe.

If you take trazodone, your prescriber will likely monitor levels of digoxin and phenytoin more closely. You may also need a lower dose of digoxin or phenytoin while taking trazodone.

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