Serotonin and norepinephrine reuptake inhibitors, also called SNRIs, are a class of medicines that are effective in treating depression. They also are sometimes used to treat other conditions, such as anxiety and long-term pain, especially nerve pain. SNRIs may be helpful if you have both long-term pain and depression.

SNRIs ease depression by affecting chemical messengers called neurotransmitters that affect mood.

SNRIs block the reabsorption, also called reuptake, of the neurotransmitters serotonin (ser-o-TOE-nin) and norepinephrine (nor-ep-ih-NEF-rin) in the brain. Blocking reabsorption makes more of these chemicals available to help ease depression symptoms.

The U.S. Food and Drug Administration, also called the FDA, has approved these SNRIs to treat depression:

• Desvenlafaxine (Pristiq).
• Duloxetine (Cymbalta, Drizalma Sprinkle). This medicine also is approved to treat generalized anxiety disorder and certain types of pain, such as fibromyalgia pain.
• Levomilnacipran (Fetzima).
• Venlafaxine (Effexor XR). This medicine also is approved to treat generalized anxiety disorder, social anxiety disorder and panic disorder.

All SNRIs work in much the same way and generally can cause the same kinds of side effects. Some people may not have any side effects. Side effects that do occur are usually mild and go away after the first few weeks of treatment. Taking medicine with food may lessen upset stomach, a common side effect. If you can't handle the side effects of one SNRI, you may have fewer side effects with a different one, as each SNRI has a different chemical makeup.

The most common possible side effects of SNRIs include:

• Upset stomach.
• Dry mouth.
• Dizziness.
• Headache.
• Sweating.

Other possible side effects may include:

• Tiredness.
• Constipation.
• Trouble sleeping.
• Less sexual desire or trouble reaching orgasm.
• Loss of appetite.

The benefits of antidepressants typically outweigh the possible side effects when depression is severe. Which antidepressant is best for you depends on several factors, such as your symptoms and any other health conditions you may have.

Ask your healthcare professional or pharmacist about the most common possible side effects for your specific medicine. Read the patient medication guide that comes with the prescription.

SNRIs are safe for most people. But sometimes they can slightly raise blood pressure, lower electrolyte levels such as sodium and worsen liver conditions. SNRIs sometimes can affect acute angle-closure glaucoma, a form of glaucoma that happens when the iris bulges and raises pressure inside the eye. Most of these safety issues can be monitored by your healthcare professional while you're taking the medicine.

Talk with your healthcare professional about safety issues before you take an SNRI, including:

• Medicine interactions. Tell your healthcare professional about any other prescription or nonprescription medicines, herbs or other supplements you're taking. Some antidepressants can cause dangerous reactions when taken with certain medicines or herbal products.

  For example, SNRIs may slightly raise your risk of bleeding, especially when you're taking other medicines that also raise the risk of bleeding. These other medicines can include ibuprofen (Advil, Motrin IB, others), aspirin, warfarin (Jantoven) and other blood thinners.

• Serotonin syndrome. Rarely, antidepressants can cause dangerously high levels of serotonin in the body. This is called serotonin syndrome. It happens most often when you take two medicines that both raise serotonin levels. This includes taking an SNRI with other antidepressants, certain pain or headache medicines, or the herbal supplement St. John's wort.

  Symptoms of serotonin syndrome include anxiety, agitation, high fever, sweating, confusion, tremors, restlessness, lack of coordination, major changes in blood pressure and rapid heart rate. Get medical help right away if you have any of these symptoms.

• Antidepressants and pregnancy. Some antidepressants may harm your baby if you take them during pregnancy or while you're breastfeeding. If you are pregnant, are thinking about getting pregnant or are breastfeeding, talk to your healthcare professional about the benefits and possible risks of antidepressants. Don't stop taking your medicine without talking with your healthcare professional first.

Most antidepressants are generally safe, but the FDA says that all antidepressants must carry boxed warnings, the strictest warnings for prescriptions. In some cases, children, teenagers and young adults under age 25 may have an increase in suicidal thoughts or behavior when taking antidepressants. This may be more likely in the first few weeks after starting the medicine or when the dose is changed. There has been no evidence that this increase in suicidal thoughts or behaviors has resulted in completed suicides.

Anyone taking an antidepressant should be watched closely for worsening depression or unusual behavior. If you or someone you know has suicidal thoughts when taking an antidepressant, call your healthcare professional right away or get emergency help.

Keep in mind that depression that's not treated is a more concerning risk factor for suicide. And antidepressants may lessen suicide risk in the long run by improving mood for many people.

Talk with your healthcare professional before you stop taking an SNRI.

SNRIs are not considered habit-forming. But stopping antidepressant treatment suddenly or missing several doses may cause some symptoms. This is sometimes called discontinuation syndrome.

Discontinuation symptoms can include:

• Dizziness.
• Headache.
• Flu-like symptoms, such as tiredness, chills and muscle aches.
• Irritability and restlessness.
• Upset stomach.
• Insomnia or sleep disturbances, such as nightmares.
• Diarrhea.

These symptoms may be more likely to happen with venlafaxine or desvenlafaxine, though they can happen when any SNRI is stopped suddenly. Work with your healthcare professional to slowly and safely lower your dose over time so you can stop the medicine safely.

Each person reacts differently to a particular antidepressant. Some people may be more likely to have certain side effects. Because of this, one antidepressant may work better for you than another. When choosing an antidepressant, your healthcare professional considers your symptoms, any health issues you have, other medicines you take and what has worked for you in the past.

Genes passed down in families may play a role in how antidepressants affect you. For some people, blood tests, where available, may offer clues about how their bodies may respond to a particular antidepressant. But other things besides genetics can affect your response to medicine.

It may take several weeks or longer before an antidepressant has a full effect. It also may take several weeks or longer for initial side effects to ease up. Your healthcare professional may recommend dose changes or a different antidepressant. With patience, you and your healthcare professional can find a medicine that works well for you.

March 06, 2025

Original article: https://www.mayoclinic.org/diseases-conditions/depression/in-depth/snris/art-20044970