Trazodone: Drug Interactions & Side Effects

Instructor: Adrianne Baron

Adrianne has a master's degree in cancer biology and has taught high school and college biology.

Trazodone is one of many drugs available to help treat depression. We are going to look at the drug interactions and side effects that come along with the benefits of this drug.


Ricky, a drug representative, is visiting Dr. Porter's office today to discuss a drug that he would like for Dr. Porter to start prescribing for her patients with depression. It is the antidepressant, trazodone. Ricky explains that trazodone is a serotonin uptake inhibitor. Serotonin is a chemical in the brain that helps to balance mood and regulate sleep patterns.

Serotonin is key for mood maintenance and sleep
Diagram of serotonin

When the right amount of serotonin is present in the brain, then a person's mood is more stable, which helps to fight depression. Uptake of too much serotonin makes the level of serotonin lower than what is required to keep mood balanced, and depression can occur.

Dr. Porter is always happy to add something new to her arsenal to help patients fight depression. As a doctor though, she has some concerns before she can comfortably prescribe trazodone to her patients. She needs for Ricky to explain the drug interactions that she needs to avoid or be cautious of and the side effects that may take place in her patients while taking trazodone.

Drug Interactions

Drugs to Avoid

Dr. Porter immediately states that any other drug that affects serotonin levels could be a dangerous interaction. Ricky confirms this and says that she shouldn't prescribe trazodone for any patient that is taking or took any MAOI or monoamine oxidase inhibitor in the last 14 days. MAOIs are medications that inhibit the enzyme that breaks down serotonin. This makes serotonin levels remain higher than they would in the presence of the enzyme. Both MAOIs and trazodone together could cause a set of symptoms known as serotonin syndrome. This includes fever, diarrhea, shivering, muscle stiffness, seizures, and possibly death.

Ricky also adds that this same effect may be seen if a patient takes it with other antidepressants such as sertraline, fluoxetine, and duloxetine, St. John's Wort, and the street drug ecstasy. These all may have effects on serotonin levels and can potentially cause serotonin syndrome.

Other Trazodone Interactions

Dr. Porter asks about drugs that may enhance or diminish the amounts of trazodone in the body. Ricky lets her know that some antifungal drugs like fluconazole, antibiotics like clarithromycin, seizure medicines like carbamazepine, and HIV protease inhibitors like ritonavir, may change the levels of trazodone in the body. Ricky reminds Dr. Porter that increasing or decreasing the amount of trazodone can have the opposite effect of taking the medication. Too much or too little serotonin can lead back to mood swings and depression.

A couple of drugs interactions result in an increase in the amount of the other drug in the body. Digoxin and phenytoin levels will likely increase in the body when they are taken with trazodone. The main concern here that Ricky explains is that an increase in these drugs also increases their side effects. Ricky advises Dr. Porter to closely monitor the amount of these drugs in the body if they are taken with trazodone.

Ricky says there is a possibility of bleeding in the stomach if trazodone is taken with blood thinners such as warfarin and non-steroidal anti-inflammatory drugs such as aspirin and ibuprofen. The best thing that Dr. Porter can do if she has a patient taking both of these drugs is to follow-up with the patient to check for this.

Alcohol should not be consumed when taking trazodone
No drinking sign

Dr. Porter says she, of course, knows that she has to be mindful of patients that are taking any drugs that cause drowsiness, such as sedatives and even alcohol. These could interact and increase the drowsiness with the risk of altering consciousness levels.

Side Effects

Dr. Porter is ready to hear the side effects that come with the benefits of trazodone. Ricky says there are a few common side effects that aren't that serious. They include headache, nausea, vomiting, diarrhea, constipation, muscle pain, and changes in erections. Dizziness is another side effect, but it can easily be relieved by getting up slowly, since it normally only occurs when changing positions from lying down to sitting or standing up.

Ricky says there are some other more concerning side effects, but they are not as common as the ones he just went over. Some people, especially teens and young adults, may become more depressed and have thoughts of committing suicide from taking trazodone. Anxiety, panic attacks, violence, and strange changes in behavior are all a part of the side effects that can happen with trazodone.

He tells Dr. Porter that some males have ended up having an erection that lasted for more than four hours as a result of taking trazodone. So she should warn her male patients of this possibility before prescribing trazodone to them.

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