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Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

Reviewed by: HU Medical Review Board | Last reviewed: September 2023

Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a type of drug used to treat depression. These drugs are often first-line treatment options for major depressive disorder (MDD).1,2

SNRIs also can be used to treat other mental health and medical conditions. These conditions include:2,3

  • Generalized anxiety disorder
  • Diabetes-related nerve pain (diabetic neuropathy)
  • Fibromyalgia
  • Chronic muscle or skeletal pain
  • Panic disorder
  • Social anxiety disorder

How do SNRIs work?

SNRIs impact the neurotransmitters serotonin and norepinephrine. Neurotransmitters are chemicals the brain uses to send signals. These signals impact mood, behavior, bodily functions, and more. Experts think changes in the levels of certain neurotransmitters, like serotonin and norepinephrine, play a role in developing depression.4,5

The body releases neurotransmitters when it needs to send signals. Afterward, it brings them back into nerve cells and recycles them to use again later. This is called the reuptake process. SNRIs prevent the reuptake of norepinephrine and serotonin. This increases the activity of these neurotransmitters. Increased activity of serotonin and norepinephrine in the brain may improve symptoms of depression.3,4,6

Some people do not respond to certain SNRIs. They may still have significant symptoms even when taking their SNRI as it is prescribed. Others may have side effects that are hard to tolerate. You and your doctor will work together to find the right option for you. For many, this is a trial-and-error process.1,2,4

Examples of SNRIs

SNRIs commonly used to treat depression in the United States are:2,3,6,7

  • Venlafaxine (Effexor®)
  • Duloxetine (Cymbalta®)
  • Levomilnacipran (Fetzima®)
  • Desvenlafaxine (Pristiq®)

Your doctor will choose an SNRI for you depending on factors like the other drugs you take, antidepressants you have tried in the past, and any other health issues you live with.1

What are the possible side effects?

SNRIs have fewer overall side effects than older drugs used to treat depression. But people taking SNRIs may still experience side effects. Side effects can vary based on the specific drug you are taking.2,3,6,7

The most common side effects of SNRIs include:2,3,6,7

  • Headache
  • Trouble sleeping (insomnia)
  • Nausea
  • Constipation or diarrhea
  • Dizziness
  • Dry mouth
  • Sweating
  • Loss of appetite
  • Issues with sexual function, such as reduced sexual desire, trouble maintaining an erection (erectile dysfunction), or problems reaching orgasm
  • Feeling tired

SNRIs have a boxed warning, the strictest warning from the US Food and Drug Administration (FDA). They have this warning because kids, teenagers, and young adults may have an increased risk of suicidal thoughts or behaviors when taking SSRIs. This risk may be highest in the first few weeks of treatment or right after changing drug dosages.6

These are not all the possible side effects of SNRIs. Talk to your doctor about what to expect when taking SNRIs. You should also call your doctor if you have any changes that concern you when taking SNRIs.

Other things to know

There are some rare side effects and possible risks to consider with SNRIs. Your doctor will cover these rare side effects when prescribing medicine.2,3,6-8

If you stop an SNRI too quickly or suddenly, you may experience withdrawal symptoms. This is often described as feeling like you have the flu, with severe muscle aches and chills, dizziness, headache, nausea, or irritability. Do not stop or change the dose of your SNRI without talking with your doctor first.2,3,6-8

If you notice any new symptoms you are not used to, seek medical guidance on how to proceed.

Before starting on an SNRI, tell your doctor if you are pregnant or planning to become pregnant. Some SNRIs are not safe to take while pregnant.1,6

Your doctor will monitor you closely for any mental health side effects when you start or change doses of an antidepressant. It is important to seek support if you notice you are having thoughts of harming yourself or others. You can call or text the Suicide & Crisis Lifeline at 988 anytime to talk to a crisis counselor. Or chat with one online.6,7,9

It can take several weeks to start feeling the effects of an antidepressant drug. You may need several dose changes along the way. The trial period for a single SNRI drug can be 6 weeks or more. If you are having bothersome side effects or your symptoms are not improving at that point, your doctor may prescribe a different drug. This may be another SNRI or a different drug altogether.1,4,5

Before beginning treatment for depression, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you take. This includes over-the-counter drugs.

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