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If you have any medical questions or concerns, please talk to your healthcare provider. The articles on Health Guide are underpinned by peer-reviewed research and information drawn from medical societies and governmental agencies. However, they are not a substitute for professional medical advice, diagnosis, or treatment.
If you research antidepressants, you’ll find that there are many options. One of the oldest antidepressants is trazodone, which has been around since the 1980s. Read on to learn more about trazodone, including its potential uses, side effects, drug interactions, and more.
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What is trazodone?
Trazodone is a prescription antidepressant medication that has been used for decades. It is available as a generic drug but has also been sold under several brand names worldwide, including Desyrel (see Important Safety Information) and Oleptro.
Like many other types of antidepressant medications, trazodone affects certain natural substances in the brain called neurotransmitters. Trazodone belongs to a class of antidepressants called serotonin antagonist and reuptake inhibitors (SARIs). It works mainly by increasing the levels of serotonin between nerve cells. Serotonin is a neurotransmitter necessary that helps facilitate communication between nerves.
Scientists don’t understand the exact mechanisms of how trazodone works. Some of its effects may be because trazodone also blocks certain other serotonin reuptake transporters and receptors, further affecting brain chemistry (Shin, 2021).
Trazodone is FDA-approved to treat major depressive disorder (MDD).
According to the National Institute of Mental Health (NIMH), major depressive disorder (often simply called depression) is one of the most common mental health disorders in the U.S. It is more than just “feeling sad” or “blue”—depression is a mood disorder that can affect all aspects of your life, like eating, sleeping, working, relationships, social life, etc. (NIMH, 2018).
Trazodone may improve your depression symptoms and help you start feeling like yourself again.
Off-label uses for trazodone
Sometimes, healthcare providers use trazodone “off-label”—this means that the FDA hasn’t approved trazodone for that specific purpose.
One of the most common off-label uses of trazodone is for treating insomnia. Everyone has had trouble sleeping because of one reason or another—work stress, relationship issues, trauma, etc. But this usually goes back to normal after a few days or weeks. Chronic insomnia lasts for a month or more and is often caused by some other problems. Common causes of sleep problems include caffeine or alcohol use, medications, medical conditions, or other sleep disorders.
Antidepressants: types, side effects, uses, and risks
You can imagine that a month of not sleeping well can wreak havoc on your body and your life. Trazodone is sometimes prescribed to help you get your sleep schedule back on track.
Other examples of off-label uses for trazodone include (Shin, 2021):
- Anxiety disorder
- Alzheimer’s disease
- Post-traumatic stress disorder (PTSD)
- Substance abuse
Trazodone side effects
- Dry mouth
- Sleepiness/decreased alertness
- Fatigue or tiredness
- Blurred vision
Less frequently, people experience severe side effects like (UptoDate, n.d.):
- Increased thoughts of suicide, especially in younger people
- Serotonin syndrome: Too much serotonin in the body can lead to agitation, hallucinations, increased body temperature, high blood pressure and heart rate, muscle tremors, vomiting, diarrhea, etc.
- Abnormal heart rhythms (arrhythmias)
- A sudden drop in blood pressure when you stand from a sitting position (orthostatic hypotension)
- Increased risk of bleeding, especially if you are taking blood thinners
- Priapism (a painful erection that lasts 4–6 hours or longer)
If you do experience side effects, do not stop trazodone suddenly. Going cold turkey can lead to discontinuation syndrome and withdrawal symptoms. Talk to your healthcare provider about discontinuing the drug slowly over time.
This list does not include all possible side effects and others may occur. Seek medical advice from your pharmacist or healthcare provider for more information.
Insomnia: what is it, symptoms, causes, treatments
Trazodone hydrochloride tablets are available in 50 mg, 100 mg, 150 mg, and 300 mg strengths. Your healthcare provider will adjust your dose based on your condition and how well the medication is working.
Trazodone drug interactions
Inform your healthcare provider about any other drugs you may be taking before starting trazodone, including over-the-counter medications and herbal supplements. Potential drug interactions include (FDA, 2017):
- Monoamine oxidase inhibitors (MAOIs): You should not use trazodone within 14 days of taking MAOIs like phenelzine, tranylcypromine, linezolid, isocarboxazid, methylene blue, and selegiline. Both trazodone and MAO inhibitors increase serotonin levels, and using them together increases your risk of serotonin syndrome.
- Drugs that increase serotonin levels (serotonergic drugs): Many medications can increase serotonin levels. Combining them with trazodone can raise the likelihood of developing serotonin syndrome. Examples of medicines that should not be taken with trazodone include tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and St. John’s wort.
- Blood thinners: Trazodone can interfere with the clotting process, increasing the likelihood of bleeding. This risk is even higher when combined with blood thinners (anticoagulants). Your healthcare provider may need to adjust your trazodone dose.
- Drugs that affect the CYP3A4 system: The CYP3A4 system of the liver breaks down trazodone. Medicines that block this system prevent trazodone from being metabolized, and more of the drug than expected ends up in your system. This can increase your risk of side effects. Alternatively, medications that increase the activity of the CYP3A4 system cause trazodone to be broken down faster than expected, making your dose less effective. If you take any medications that affect the CYP3A4 system, your healthcare provider may adjust your trazodone dose.
- Digoxin and phenytoin: Trazodone can increase the levels of digoxin or phenytoin.
- Drugs that cause QT prolongation: Certain medications affect your heart rhythm by lengthening the QT interval, a part of the electrical process in the heart. Combining these types of drugs with trazodone raises the risk of developing abnormal heart rhythms or arrhythmias.
- CNS depressants: Drugs that slow down the central nervous system (CNS) should not be combined with trazodone because it enhances the effects (and potential toxicity) of the CNS depressants. Examples include alcohol and sleeping pills.
This list does not include all possible drug interactions with trazodone and others may occur. Talk to your pharmacist or healthcare provider for more information.
SSRIs: everything you need to know
There is a black box warning from the U.S. Food and Drug Administration (FDA) on all antidepressants, including trazodone. These drugs have an increased risk of suicidal thoughts and behaviors in children, teenagers, and young adults. Families and caregivers should be aware of this risk, especially during the first few months of therapy or after a dose increase. Be on the lookout for suicidal thoughts, attempts, or other mood changes. Trazodone is not FDA-approved for use in people under 18 years of age (FDA, 2017).
Certain groups of people are at higher risk of adverse effects with trazodone and should avoid using it or use it with caution and careful monitoring. Examples of these groups include (UptoDate, n.d.):
- Pregnant or nursing women: According to the FDA, trazodone is Pregnancy Category C, meaning there is not enough data to say whether or not trazodone is safe during pregnancy (FDA, 2017). Also, research shows that trazodone enters breast milk. However, when deciding whether or not trazodone is the proper treatment while nursing, you and your healthcare provider should consider both the potential risks to the baby and the benefits to the mother.
- Older adults: People over 65 may be at a higher risk of developing low sodium (hyponatremia) while taking trazodone.
- People with bipolar disorder: Trazodone can trigger a manic or hypomanic episode in people with bipolar disorder. Trazodone is not FDA-approved to treat bipolar disorder and should be avoided in this group.
- People who have or who are at risk for angle-closure glaucoma: Trazodone may trigger an episode of angle-closure glaucoma (high eye pressure, eye pain, eye redness, blurred vision, halos around lights) that can lead to permanent vision loss. Angle-closure glaucoma usually only occurs in people with “narrow angles in the eye”—meaning that the front part of the eye is shallower than average. Your healthcare provider may recommend an eye exam before starting trazodone.
- People with liver or kidney disease: These groups may develop higher than desired levels of trazodone and may need to adjust their dose.
- People with a severe allergic reaction to trazodone (e.g., rash, itching, hives, trouble breathing, etc.) should not take trazodone.
This list does not include all at-risk groups. Talk to your healthcare provider or pharmacist for more information.
- National Institute of Mental Health. (2018). Depression. Retrieved on Aug 3, 2021 from https://www.nimh.nih.gov/health/topics/depression/index.shtml
- Shin JJ, Saadabadi A. (2021). Trazodone. In: StatPearls [Internet]. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK470560/
- UpToDate. (n.d.). Trazodone: Drug information. Retrieved on Aug 3, 2021 from https://www.uptodate.com/contents/trazodone-drug-information
- U. S. Food and Drug Administration (FDA). (2017). Desyrel (trazodone hydrochloride). Retrieved on Aug 3, 2021 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018207s032lbl.pdf
Dr. Mike is a licensed physician and the Director, Medical Content & Education at Ro.