Serotonin-norepinephrine reuptake inhibitor (SNRI) medications are antidepressant drugs that doctors may prescribe to treat depression, anxiety, and some forms of chronic pain. SNRIs may improve mood by influencing the levels of certain chemicals in the brain.

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This article will look at how SNRI drugs work, what they can treat, and their potential risks and side effects.

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SNRIs are a class of antidepressants. The Food and Drug Administration (FDA) approved the first SNRI for use in the United States in 1993. Since then, it has approved several more.

SNRI medications increase the amounts of serotonin and norepinephrine available in the brain. Typically, the nerve cells reabsorb these substances, but SNRIs block this reabsorption.

Serotonin and norepinephrine are hormones and neurotransmitters, which pass messages between nerve cells in the brain. Serotonin is the key hormone that stabilizes mood, while norepinephrine influences emotions, alertness, and energy.

The FDA has approved the following SNRIs in the U.S.

Generic nameBrand nameUse
desvenlafaxinePristiq, Khedezladepression
levomilnacipranFetzimadepression
duloxetineCymbalta• depression
generalized anxiety disorder (GAD)
• chronic musculoskeletal pain
• diabetic peripheral neuropathic pain
fibromyalgia
venlafaxineEffexor, Effexor XR• depression
• GAD
panic disorder
social anxiety disorder
milnacipranSavellafibromyalgia

Other countries, including those in Europe and Asia, have approved the use of milnacipran for treating depression. Therefore, some U.S. doctors may prescribe it off-label for that purpose.

SNRIs can help treat the following mental health conditions.

Depression

Doctors can prescribe SNRIs for the treatment of depression or major depressive disorder.

Some people respond well to SNRIs, while others respond better to selective serotonin reuptake inhibitors (SSRIs) or other types of antidepressants.

A period of trial and error may be necessary for people to find the best medication for their needs.

Learn more about the difference between SNRIs and SSRIs here.

Anxiety disorders and panic disorder

Some SNRIs may be beneficial for those with anxiety or panic disorders.

According to Mental Health America, some people may find SNRIs to be helpful in treating anxiety. Others may prefer to use SSRIs for this purpose.

Some research in children and adolescents with anxiety found that their responses to SNRIs and SSRIs were varied.

The researchers found that SSRIs may lead to faster and more significant improvements in anxiety symptoms. However, SNRIs may have fewer side effects, and they may cause less “restlessness,” which could be an important consideration for those with anxiety.

Chronic pain

SNRIs can also help treat some chronic pain conditions, including fibromyalgia, chronic musculoskeletal pain, and diabetic peripheral neuropathic pain.

Some research has indicated that duloxetine may reduce fibromyalgia pain, while venlafaxine may significantly improve fibromyalgia and neuropathic pain.

These SNRIs appear to be more effective than SSRIs for chronic pain relief. SSRIs seem to have limited effectiveness for this purpose.

Obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) affects 2.2 million adults in the U.S. OCD can be challenging to treat, and a combination of treatments is often necessary.

Research into the role of SNRIs for OCD is lacking, though the limited available research has suggested that they may have benefits for some people with this condition.

Attention deficit hyperactivity disorder

Occasionally, doctors prescribe venlafaxine to treat some symptoms of attention deficit hyperactivity disorder (ADHD).

Although it has approval for use in children and adolescents, doctors may reserve its use for adults who do not respond well to other ADHD medications.

In one 2012 study in adults, there was a decrease in ADHD symptoms after 6 weeks of taking either venlafaxine or a placebo.

There was a significant difference between these treatments. Those taking venlafaxine self-reported a significant treatment response compared with those in the placebo group.

According to the National Health Service (NHS), some side effects of SNRIs can include:

These side effects should improve within a few weeks, though there is a chance that they may persist.

SNRIs are safe for most people. However, some potential risks and safety concerns include the following.

Drug-induced liver toxicity

Some research has indicated that this affects 0.5% to 1% of those taking SNRIs or SSRIs, with duloxetine more likely than other SNRIs to cause issues.

Elevated blood pressure

Venlafaxine, desvenlafaxine, and levomilnacipran may cause an increase in blood pressure.

According to a 2016 article, venlafaxine can cause a clinically significant increase in diastolic blood pressure.

Desvenlafaxine and levomilnacipran can also increase a person’s blood pressure, though to a lesser extent.

Drug interactions

SNRIs may react with some other medications.

A person should tell a doctor if they are taking any other medications, supplements, or herbal remedies.

The FDA states that people should avoid taking SNRIs alongside monoamine oxidase inhibitors (MAOIs). MAOIs are another medication class that a person can take to treat depression.

MAOIs can have dangerous interactions with other medications, however. A person should always consult a doctor before taking any medications alongside MAOIs.

Serotonin syndrome

Serotonin syndrome occurs when there are high serotonin levels in the body.

It may develop if a person takes two antidepressants together. It can also occur if a person is taking an SNRI alongside certain pain medications or herbal treatments, such as St. John’s wort.

Some symptoms of serotonin syndrome include agitation, confusion, and a rapid heart rate.

It is important to seek immediate medical attention for serotonin syndrome.

Suicidal thoughts or behaviors

Some antidepressants, such as venlafaxine, may increase suicidal thoughts or behaviors in those under 25 years of age — particularly in the first few weeks of treatment.

Suicide prevention

If you know someone at immediate risk of self-harm, suicide, or hurting another person:

  • Ask the tough question: “Are you considering suicide?”
  • Listen to the person without judgment.
  • Call 911 or the local emergency number, or text TALK to 741741 to communicate with a trained crisis counselor.
  • Stay with the person until professional help arrives.
  • Try to remove any weapons, medications, or other potentially harmful objects.

If you or someone you know is having thoughts of suicide, a prevention hotline can help. The 988 Suicide and Crisis Lifeline is available 24 hours a day at 988. During a crisis, people who are hard of hearing can use their preferred relay service or dial 711 then 988.

Find more links and local resources.

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Risk of overdose

It is possible to overdose on antidepressants.

To lower the risk of overdose, a person should take their SNRI as a doctor prescribed.

If someone has overdosed on antidepressants, call 911 immediately.

Learn more about overdosing on antidepressants here.

SNRIs may cause complications during pregnancy. However, depression in the birthing parent may also adversely affect the fetus’s development.

Therefore, pregnant people should be sure to talk with a doctor to discuss the risks and benefits of antidepressant use during pregnancy. When the benefits outweigh the risks, it may be necessary to take an SNRI during pregnancy.

Learn more about antidepressant use during pregnancy here.

Doctors tend to recommend that people avoid consuming alcohol when taking antidepressants. This is because alcohol can:

  • worsen the symptoms of depression, including suicidal thoughts and behaviors
  • make treatment more challenging
  • increase the risk of antidepressant side effects
  • worsen antidepressant side effects
  • increase the risk of overdose

Combining antidepressants and alcohol can also put additional pressure on the liver, which can lead to liver problems.

However, some people may be reluctant to avoid alcohol completely. Therefore, the National Alliance on Mental Illness recommends that those who do wish to continue drinking alcohol while taking antidepressants do so in the safest way possible.

Some doctors advise that females taking antidepressants consume no more than one alcoholic drink per day and that males taking antidepressants consume no more than two alcoholic drinks per day. They also recommend consuming the alcohol with food, and drinking it slowly.

Individuals may wish to stop taking SNRIs for various reasons. For example, this may be due to side effects or an improvement in their depression symptoms.

It is important that people do not stop taking antidepressants without speaking with a doctor first. Abruptly stopping this treatment can cause withdrawal symptoms or a return of depression.

Doctors can help people gradually and safely decrease their dosage to reduce withdrawal symptoms. They can also help monitor for depression relapse.

Learn more about antidepressant withdrawal here.

SNRIs may benefit some people, but they may not benefit everyone. It is not possible to say if a particular drug will work well for someone. Usually, a period of trial and error is necessary to find the right drug and dosage for a person.

There are many other classes of antidepressants as well as other treatments for depression, such as individual or group therapy. Making certain lifestyle changes, such as getting more regular exercise, may also help ease the symptoms of depression.

Learn more about the mental health resources available here.

People who wish to try antidepressants should discuss their options with a doctor. When prescribing treatments, doctors will consider the person’s symptoms, general health, and use of other medications.

Some questions to ask a doctor about SNRIs include:

  • What side effects could this medication cause?
  • How long will the side effects last?
  • How effective is this medication for my condition?
  • Does it interact with other medications or supplements?
  • Will it affect my sex drive or other aspects of sexual functioning?
  • Can I take this medication during pregnancy or while nursing?
  • Can I use alcohol or other drugs with this medication?
  • What other medications are available for my condition?
  • What non-medication treatment options are there for my condition?

Some other points to discuss include:

  • symptoms experienced while taking other or similar medications
  • any personal or family history of mental health issues or suicide concerns
  • any allergies

SNRIs are a class of antidepressants that may help relieve the symptoms of depression, anxiety, or chronic pain in some people. They can cause side effects, though these are typically mild or temporary.

If SNRIs do not work, there are many other medications and non-medication treatment options for depression. It is important to keep trying to find a suitable treatment. Around 80–90% of people with depression eventually respond well to treatment.