Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

SNRIs are drugs that treat mental health disorders and other conditions. Here is an overview of their actions, benefits and risks.

SNRIs are important medications that help treat symptoms of depression, anxiety, chronic nerve-related pain and other conditions. These medications have helped reshape the way many conditions are treated. There are important features of these SNRIs that must be understood by anyone considering them, including their potential benefits and risks.

What are SNRIs?

Serotonin-norepinephrine reuptake inhibitors (SNRIs) are a class of medications which help readjust how the body processes norepinephrine. Norepinephrine, dopamine and serotonin are important chemical messengers in the body and the brain called monoamines. These chemicals are responsible for conveying information about mood, anxiety levels, pain and other functions.

This understanding of how SNRIs work helps explain what SNRIs are used for. SNRIs are used for treating major depressive disorder, several types of anxiety disorders, chronic pain (particularly for pain originating from nerve cells, called “neuropathic pain”) and fibromyalgia.  

Background & History

The history of SNRIs begins in an unlikely place: the treatment of tuberculosis. In the 1950s, a drug being researched as a cure for tuberculosis was found to substantially increase the energy, mood and outlook of patients who took it. Further research showed that the drug made monoamines more available to the brain, which allowed the first generation of antidepressants to develop.

Even though those medications were limited by the presence of serious side effects, they helped scientists understand the role of these important monoamine chemicals and paved the way for developing the second generation of antidepressants, which includes SNRIs. These medications had far fewer serious side effects and were better tolerated. In 1993, venlafaxine (branded as Effexor), became the first SNRI on the market.

Use in Treating Mental Illness

SNRIs are considered first-line treatments for conditions such as major depressive disorder. In addition to using SNRIs for depression, providers prescribe SNRIs for anxiety disorders, including generalized anxiety disorder, obsessive-compulsive disorder and panic disorder. They are the second most prescribed class of antidepressants. Like other antidepressants, SNRIs may require up to eight weeks before showing significant benefits.

How Do SNRIs Work?

From the name, you can tell which chemical messengers SNRIs act on — serotonin and norepinephrine. But what do SNRIs do? These medications work by preventing nerve cells from reabsorbing serotonin and norepinephrine from the communication space between one nerve cell in the brain and another.

The more these molecules are available in the communication space, the more the nerve cells get positive messages about a person’s mood, energy, outlook, pain level and state of mind.

SNRIs vs. SSRIs

Selective serotonin reuptake inhibitors, or SSRIs, are another class of antidepressants with actions, benefits, side effects and potential risks that are fairly similar to those of SNRIs. Though individual results vary, both classes of medication have been shown to be equally effective in the treatment of depressive and anxiety disorders.

The primary difference when it comes to SSRIs vs SNRIs is in the action of norepinephrine, on which SSRIs have no effect. That difference allows some of the SNRIs to be particularly effective in controlling neuropathic pain or attention deficit hyperactivity disorder (ADHD).

Types of SNRIs

Examples of SNRIs include the following.

• Desvenlafaxine (Pristiq)
  • FDA approved for treatment of major depressive disorder
• Duloxetine (Cymbalta)
  • FDA approved for treatment of major depressive disorder, generalized anxiety disorder, fibromyalgia, diabetic neuropathy and several pain disorders
• Milnacipran (Savella)
  • FDA approved for treatment of fibromyalgia
• Venlafaxine (Effexor)
  • FDA approved for treatment of major depressive disorder, generalized anxiety disorder, social anxiety disorder and panic disorder
• Levomilnacipran (Fetzima)
  • FDA approved for treatment of major depressive disorder
• Tramadol (Ultram)
  • FDA approved for the treatment of moderate to moderately severe pain. Note that tramadol also has opioid properties and is usually first considered an opioid.
• Atomoxetine (Strattera)
  • FDA approved for the treatment of ADHD

Effectiveness of SNRIs

Studies have shown that SNRIs are equally as effective at treating depression and anxiety as other antidepressant medications. SNRIs are often chosen by providers in consultation with their patients about which side effects are tolerable, or which side effects may even be therapeutic.

Side Effects of SNRIs

Common SNRI short- and long-term side effects can include:

• Nausea
• Lightheadedness
• Sweating
• Headache
• Agitation
• Sexual dysfunction

Risks Associated with SNRIs

One of the most significant SNRI risks (especially if combined with SSRIs or opioids) is the possibility of serotonin syndrome, a condition marked by serotonin overexposure. This syndrome is usually mild, but in rare cases, it can be fatal. Symptoms of serotonin syndrome include:

• Sweating
• Temperature elevation
• Agitation
• Increased reflexes
• Tremors
• Diarrhea

Like other antidepressants, SNRIs can cause an increase in suicidal thinking, especially among youth and young adults.

Possible Interactions

The most significant potential SNRI drug interaction is with SSRIs or opioids as described above, due to the potential for serotonin syndrome.

Taking SNRIs While Pregnant

All of the medications in the SNRI class are classified as pregnancy class C by the FDA. This means that while research may show minor harm to an animal fetus when taking an SNRI, human research on potential fetal harm from taking an SNRI while pregnant is inadequate.

In order to make a determination about whether to take an SNRI while pregnant, a woman and her provider must weigh the risks and benefits of continuing the medication against the risks and benefits of stopping it.

Stopping SNRIs

Similar to SSRIs, suddenly stopping SNRIs without a gradual decrease can lead to a withdrawal-like syndrome called antidepressant discontinuation syndrome. While it is unclear why the discontinuation syndrome happens, its symptoms are generally consistent:

• Flu-like symptoms
• Fatigue
• Insomnia
• Nausea
• Poor balance
• Sensory changes

One of the most well known of those “sensory changes” is “brain zaps” — the feeling of painful electrical pulses within the skull. These and other symptoms of a discontinuation syndrome can be reversed by taking the medication again, and the symptoms can be reduced by gradually decreasing the dose of an SNRI.

What to Do In Case of Overdose

SNRI overdoses are relatively common and, like all overdoses, should be treated as medical emergencies. Emergency services such as 911 should be activated. However, most second-generation antidepressants are not fatal to consume in excess, and survival rates for SNRI overdose are high.

Get More Information on SNRIs

SNRIs are important medications that treat many conditions. If you would like to learn more about SNRIs, The Recovery Village has a wealth of information available about them and the conditions they treat.

If you or a loved one are suffering from a condition that requires an SNRI for treatment, you are not alone. The Recovery Village has helped many people recover from addiction and co-occurring mental health conditions. Call or chat with The Recovery Village today.

Editor – Jonathan Strum

Jonathan Strum graduated from the University of Nebraska Omaha with a Bachelor's in Communication in 2017 and has been writing professionally ever since. Read more

Medically Reviewed By – Dr. Kevin Wandler, MD

Kevin Wandler holds multiple positions at Advanced Recovery Systems. In addition to being the founding and chief medical director at Advanced Recovery Systems, he is also the medical director at The Recovery Village Ridgefield and at The Recovery Village Palmer Lake. Read more