Drug Classes

Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

Yvette Brazier
By
Angela D. Harper, MD
by
Updated on October 17, 2024

Selective norepinephrine reuptake inhibitors (SNRIs) are a type of antidepressant medication. They can also help treat anxiety, chronic pain, and the symptoms of fibromyalgia.

What Are SNRIs?

SNRIs have approval from the U.S. Food and Drug Administration (FDA) to treat the symptoms of depression, anxiety disorders, chronic nerve pain, and other health conditions. They do this by changing how neurotransmitters in the brain communicate with each other. They block the reabsorption of serotonin and norepinephrine to help regulate mood.

Research suggests that roughly 15 percent of people in the United States live with mild to moderate depression, while just over 7 percent have severe depression. SNRIs and other antidepressants, like selective serotonin reuptake inhibitors (SSRIs), can help manage those symptoms.

What Conditions Do SNRIs Treat?

SNRIs are classified as antidepressants, but they are prescribed to treat health conditions beyond low mood. While SNRIs are FDA approved to treat symptoms of depression and other conditions, doctors can also prescribe SNRIs off-label for other health problems.

Your doctor might prescribe SNRIs as an FDA-approved treatment if you have:

They might prescribe an SNRI off-label if you have:

Types of SNRIs

SNRIs are not sold over the counter; they are only available by prescription. Some common types include:

  • desvenlafaxine (Pristiq)
  • duloxetine (Cymbalta)
  • milnacipran (Savella)
  • venlafaxine (Effexor)
  • levomilnacipran (Fetzima)

How Do SNRIs Work?

Serotonin is known as a “feel good” hormone, while norepinephrine boosts energy and alertness. SNRIs increase the levels of both of these hormones, which are also neurotransmitters that carry messages to different parts of the body.

Serotonin is a brain hormone that helps regulate mood, bowel function, and the sleep-wake cycle. When serotonin levels are just right, you will likely feel more focused, calmer, happier, and more emotionally stable.

Norepinephrine is an endocrine hormone that plays a role in the sleep-wake cycle, helping you feel more alert. Low levels of norepinephrine have been linked to lethargy, difficulty focusing, and low mood.

Another class of drugs, SSRIs, also treat mood disorders like depression and other conditions by raising serotonin levels.

What Are the Possible Side Effects of SNRIs?

Most side effects from SNRIs improve with time. But if they persist or are severe, it’s best to speak with your healthcare provider about your concerns. Possible side effects include:


Are There Any Risks Related to SNRIs?

Some people who take an SNRI for depression are more likely to have suicidal thoughts and behaviors when on this medication. Because of this, all SNRIs are required to carry a black box warning on the labeling that states that the drug has a significant risk for serious or life-threatening adverse effects.

SNRIs can also interact with other drugs, strengthening or weakening the effect of the SNRI or the other medication. For instance, you can’t take an SNRI if you are already using a monoamine oxidase inhibitor (MAOI) antidepressant, since this combination will disrupt the effects of both drugs.

 A doctor may need to monitor your use of SNRIs if you:

  • Have kidney or liver problems
  • Are pregnant or breastfeeding
  • Use certain other drugs, such as anticoagulants
  • Have narrow-angle glaucoma
  • Have high blood pressure
  • Are under 18 years old

Your doctor may not prescribe SNRIs if you already take:

  • Other drugs that affect serotonin levels, such as SSRIs, lithium, or St John’s wort
  • A (CYP) 3A4 inhibitor, such as amiodarone or ketoconazole
  • Some weight loss agents
It’s also possible to have too much serotonin-related activity in your central nervous system. Serotonin syndrome is a potentially life-threatening condition that can happen if you take too much of your SNRI or if you use an SNRI along with another serotonin-boosting drug. Always make sure your doctor knows about any other health conditions you have and any other drugs you are taking.

The Takeaway

Serotonin and norepinephrine reuptake inhibitors (SNRIs) are prescription drugs that treat depression, anxiety disorders, fibromyalgia, and other medical conditions. They do this by changing how neurotransmitters in the brain communicate with each other. They can also have adverse effects on mood, so your doctor can help you decide if an SNRI is suitable for you.

Editorial Sources and Fact-Checking

Everyday Health follows strict sourcing guidelines to ensure the accuracy of its content, outlined in our editorial policy. We use only trustworthy sources, including peer-reviewed studies, board-certified medical experts, patients with lived experience, and information from top institutions.

Sources

  1. Serotonin and norepinephrine reuptake inhibitors (SNRIs). Mayo Clinic. October 2019.
  2. Zhang Z et al. Depressive Symptoms and Mortality Among US Adults. JAMA Network Open. October 9, 2023.
  3. SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors). Cleveland Clinic. May 2023.
  4. Brain hormones. The Endocrine Society. January 2022.
  5. Adrenal Hormones. The Endocrine Society. January 2022.
  6. Depression Medicines. Food and Drug Administration. November 2019.
  7. Sheffler ZM et al. Antidepressants. StatPearls. May 2023.
  8. Fornaro M et al. The FDA “Black Box” Warning on Antidepressant Suicide Risk in Young Adults: More Harm Than Benefits? Frontiers in Psychiatry. May 3, 2019.
  9. Laban TS et al. Monoamine Oxidase Inhibitors (MAOI). StatPearls. July 17, 2023.
  10. Label: VENLAFAXINE HYDROCHLORIDE capsule, extended release. National Library of Medicine Dailymed. March 2024.
  11. Label: CYMBALTA- duloxetine hydrochloride capsule, delayed release. National Library of Medicine Dailymed. August 2023.
  12. Label: SAVELLA- milnacipran hydrochloride tablet, film coated. National Library of Medicine Dailymed. July 2010.
  13. Label: FETZIMA- levomilnacipran hydrochloride capsule, extended release FETZIMA- levomilnacipran hydrochloride kit. National Library of Medicine Dailymed. April 2024.
  14. Label: DESVENLAFAXINE tablet, extended release. National Library of Medicine Dailymed. August 2023.
  15. Simon LV et al. Serotonin Syndrome. StatPearls. March 2024.
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Angela-Harper-bio

Angela D. Harper, MD

Medical Reviewer

Angela D. Harper, MD, is in private practice at Columbia Psychiatric Associates in South Carolina, where she provides evaluations, medication management, and psychotherapy for adults.  

A distinguished fellow of the American Psychiatric Association, Dr. Harper has worked as a psychiatrist throughout her career, serving a large number of patients in various settings, including a psychiatric hospital on the inpatient psychiatric and addiction units, a community mental health center, and a 350-bed nursing home and rehab facility. She has provided legal case consultation for a number of attorneys.

Harper graduated magna cum laude from Furman University with a bachelor's degree and cum laude from the University of South Carolina School of Medicine, where she also completed her residency in adult psychiatry. During residency, she won numerous awards, including the Laughlin Fellowship from the American College of Psychiatrists, the Ginsberg Fellowship from the American Association of Directors of Psychiatric Residency Training, and resident of the year and resident medical student teacher of the year. She was also the member-in-training trustee to the American Psychiatric Association board of trustees during her last two years of residency training.

Harper volunteered for a five-year term on her medical school's admission committee, has given numerous presentations, and has taught medical students and residents. She currently supervises a nurse practitioner. She is passionate about volunteering for the state medical board's medical disciplinary commission, on which she has served since 2015.

She and her husband are avid travelers and have been to over 55 countries and territories.

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Yvette Brazier

Author

Yvette Brazier's career has focused on language, communication, and content production, particularly in health education and information. From 2005 to 2015, she supported learning in the health science department of a higher education establishment, teaching the language of health, research, and other language application skills to paramedic, pharmacy, and medical imaging students.

From 2015 to 2023, Yvette worked as a health information editor at Medical News Today and Healthline. Yvette is now a freelance writer and editor, preparing content for Everyday Health, Medical News Today, and other health information providers.

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