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Can you take trazodone and Prozac together?

Learn how trazodone and Prozac interact, the dangers of serotonin syndrome, and expert advice on combining these antidepressants safely.
Wendy Wisner
By | Updated on Dec. 3, 2024 Medically reviewed by Keith Gardner, R.Ph.
Rx pill bottles: Can you mix Can you take trazodone and Prozac

Key takeaways

  • Prozac and trazodone can be safely taken together if prescribed by an experienced healthcare provider.

  • The greatest risk of combining Prozac and trazodone is serotonin syndrome, which is when excessive amounts of serotonin build up in your system.

  • Trazodone is typically prescribed for insomnia or anxiety among people taking Prozac for depression.

In this article:

Prozac is the brand name for fluoxetine, which is a selective serotonin reuptake inhibitor (SSRI) antidepressant that’s FDA-approved to treat major depressive disorder in people aged eight and up. Trazodone, also known by the brand name Desyrel, is a medication that’s also FDA approved to treat major depressive disorder. It’s additionally often prescribed off-label to treat insomnia, anxiety, substance abuse disorders, Alzheimer’s disease, bulimia, and fibromyalgia.

If you are taking either Prozac or trazodone, you might be wondering: Can you take trazodone and Prozac together? The answer is that combining trazodone and Prozac can be safe, but a small number of people may experience a rare condition called serotonin syndrome, which is when too much serotonin builds up in your central nervous system due to taking too many medications that increase serotonin.

Here, we’ll go over everything you need to know about taking trazodone and Prozac together, including potential risks, benefits, side effects, precautions, and drug interactions.

Can you take trazodone and Prozac together?

Many people who use antidepressant medications like Prozac want to know: Can you take trazodone and Prozac at the same time? For instance, some patients who take Prozac may be looking for an effective insomnia treatment, and want to know if they can take trazodone to help them sleep. Others might be looking to treat some of the other off-label uses of trazodone, such as anxiety or fibromyalgia, while also taking Prozac.

Susan Trachman, MD, board-certified psychiatrist, says that most individuals can safely take these two medicines at the same time, provided they are under a doctor or psychiatrist’s supervision, and that they are prescribed at appropriate doses. “I have been in practice for over 30 years and have often prescribed these two medications together,” she says.

According to Ryan S. Sultan, MD, psychiatrist and therapist at Integrative Psych and Columbia University, taking trazodone and Prozac together is usually safe, but it’s important to understand the potential risks. “Both medications affect serotonin levels, so combining them carries a low but real risk of serotonin syndrome, especially at higher doses,” he says.

Dr. Sultan adds that the risk may depend on the specific conditions being treated, whether it be depression or insomnia. For example, sometimes low doses of trazodone are prescribed for sleep, reducing the likelihood of it interacting adversely with Prozac, which is typically prescribed for mood stabilization. Your physician will help you figure out the best way to take these two medicines. “Always consult a healthcare provider before combining these medications,” Dr. Sultan emphasizes.

Julian Lagoy, MD, a board-certified psychiatrist with Mindpath Health, says that he prescribes these two medications together frequently without complications. “Generally, I prescribe trazodone in very low doses, primarily to be used as a sleeping aid,” he says. “I would be careful if you are giving high doses of trazodone with Prozac since the medication interaction risk is much higher.”

Benefits of taking trazodone and Prozac at the same time

There are several potential benefits to taking trazodone and Prozac together.

First, says Dr. Sultan, these two medications have different modes of action and produce different effects on the body. As such, they may benefit you in different ways. Prozac works by increasing serotonin levels in the body by inhibiting reuptake. On the other hand, trazodone, especially when prescribed in low doses, can work as a sedative. Trazodone has mild serotonin receptor modulation, Dr. Sultan explains.

In general, Prozac “may improve mood and energy levels,” whereas trazodone “may alleviate insomnia or anxiety,” Dr. Sultan describes. And who might wish to combine them? “This combination might appeal to patients needing both antidepressant and sedative effects,” he says.

In particular, people tend to turn to trazodone for its sleep-inducing effects. “Trazodone is often prescribed off-label for sleep because it has hypnotic properties,” says Mike McGrath, MD, board-certified psychiatrist and chief clinical officer of The Ohana Hawaii, who adds that trazodone is quite effective at treating sleep issues. Many patients ​who combine trazodone and Prozac find that they can effectively and simultaneously treat their depressive symptoms and their insomnia.

Trazodone and Prozac risks and interactions

The biggest concern about taking trazodone and Prozac together is the risk of serotonin syndrome, a condition that occurs when too much serotonin circulates through the central nervous system. Serotonin is a neurotransmitter that modulates mood and behavior. We all produce serotonin naturally. When we take medications, drugs, or supplements that increase our levels of serotonin, we run the risk of producing too much serotonin.

Serotonin syndrome is relatively uncommon and typically manageable. In very rare instances, serotonin syndrome can result in hospitalization or death. Symptoms of serotonin syndrome include:

  • Restlessness
  • Agitation
  • Racing heartbeat
  • Elevated blood pressure
  • Diarrhea
  • Coordination issues
  • Nausea
  • Vomiting
  • Hallucinations
  • Atypical eye movements
  • Overactive reflexes

So, how likely are you to get serotonin syndrome if you take Prozac and trazodone together? Though definitely a concern, the risk is low to most patients who take these medications together, especially when prescribed by an experienced healthcare professional. Although the risk exists with any medication that increases serotonin in the body, SSRIs like Prozac are less likely to cause serotonin syndrome than monoamine oxidase inhibitors (MAOIs) like Marplan or Nardil.

Dr. Trachman says that she frequently prescribes trazodone and Prozac together. “The only time I sent a patient to the emergency room for what I suspected was serotonin syndrome occurred when a different specialist added a prescription that interacted with those I had prescribed,” she says, adding that, in general, mild serotonin syndrome is treatable, even if you develop it. “The management of serotonin syndrome is supportive care, i.e., lowering blood pressure and fluids for gastrointestinal symptoms,” she describes.

Dr. Sultan agrees that though the risk is there for serotonin syndrome, the risk is low, and increases if you take larger-than-normal amounts. “The risk increases with higher doses or additional serotonergic medications,” Dr. Sultan explains. Besides serotonin syndrome, Dr. Sultan warns against excessive sedation and cognitive impairment that may result after combining trazodone and Prozac. “Trazodone’s sedative effects may exacerbate drowsiness, particularly if fluoxetine heightens trazodone’s effects,” Dr. Sultan says.

Besides dosage and other medication reactions, Dr. Sultan says that age and underlying medications are other factors to take into consideration when combining trazodone and Prozac. “Elderly patients or those with underlying cardiac conditions are at higher risk of QT prolongation, arrhythmias, or drug interactions,” Dr. Sultan notes.

The bottom line? Always stay in close touch with your provider if you are taking trazodone and Prozac together, and never take them unless they were prescribed together.

How long after taking trazodone can you take Prozac?

There is no set recommendation regarding how to take trazodone and Prozac together. If you do take them together, your healthcare provider will help you devise a dosing schedule that works for you.

Dr. Lagoy says that he usually doesn’t prescribe these both at the same time to start. “I usually wait at least a week or two before adding the second medication,” he says. “I prefer not to start two medications at the same time because if there is a side effect, I want to know which medication caused it.”

Dr. Sultan agrees that a gradual approach is best when combining trazodone and Prozac. “If both are prescribed, start with the lowest effective doses and titrate slowly, with close monitoring by a healthcare provider,” he recommends.

What medications should you not take with trazodone or Prozac? 

In addition to interactions between trazodone and Prozac, it’s important to understand the potential interactions between trazodone and Prozac and other medications.

The following precautions should be considered when taking trazodone:

  • Monoamine oxidase inhibitors (MAOIs) should not be taken within 14 days of starting trazodone therapy
  • You should also talk to your provider if you are taking St. John’s wort, tryptophan, aspirin, or NSAIDs (ibuprofen and naproxen) with trazodone

Additionally, these medications should not be mixed with Prozac:

Sources