Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

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Yvette BrazierMedically Reviewed

Angela D. Harper, MD

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:

  • Major depressive disorder
  • Generalized anxiety disorder
  • Social anxiety disorder
  • Panic disorder
  • Pain due to diabetic neuropathy
  • Fibromyalgia
  • Chronic musculoskeletal pain

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

  • Hot flashes and night sweats due to menopause
  • Peripheral neuropathy, or nerve pain, resulting from chemotherapy
  • Urinary incontinence
  • Attention deficit hyperactivity disorder (ADHD)
  • Obsessive-compulsive disorder (OCD)
  • Migraine
  • Headache

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:

  • Nausea and vomiting
  • Dry mouth
  • Constipation
  • Fatigue
  • Drowsiness
  • Sexual dysfunction
  • High blood pressure
  • Headache
  • Excessive sweating, known as diaphoresis
  • Unusual bleeding or bruising
  • Seizures, in rare cases

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.

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