Serotonin and norepinephrine reuptake inhibitors (SNRIs)

November, 15th, 2023

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Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a class of medications that are effective in treating depression. SNRIs are also sometimes used to treat other conditions, such as anxiety disorders and long-term (chronic) pain, especially nerve pain. SNRIs may be helpful if you have chronic pain in addition to depression.

How SNRIs work

SNRIs ease depression by affecting chemical messengers (neurotransmitters) used to communicate between brain cells. Like most antidepressants, SNRIs work by ultimately effecting changes in brain chemistry and communication in brain nerve cell circuitry known to regulate mood, to help relieve depression.

SNRIs block the reabsorption (reuptake) of the neurotransmitters serotonin (ser-o-TOE-nin) and norepinephrine (nor-ep-ih-NEF-rin) in the brain.

SNRIs approved to treat depression

The Food and Drug Administration (FDA) has approved these SNRIs to treat depression:

• Desvenlafaxine (Pristiq)
• Duloxetine (Cymbalta) — also approved to treat anxiety and certain types of chronic pain
• Levomilnacipran (Fetzima)
• Venlafaxine (Effexor XR) — also approved to treat certain anxiety disorders and panic disorder

Side effects and cautions

All SNRIs work in a similar way and generally can cause similar side effects, though some people may not experience any side effects. Side effects are usually mild and go away after the first few weeks of treatment. Taking your medication with food may reduce nausea. If you can’t tolerate one SNRI, you may be able to tolerate a different one, as each SNRI varies in chemical makeup.

The most common possible side effects of SNRIs include:

• Nausea
• Dry mouth
• Dizziness
• Headache
• Excessive sweating

Other possible side effects may include:

• Tiredness
• Constipation
• Insomnia
• Changes in sexual function, such as reduced sexual desire, difficulty reaching orgasm or the inability to maintain an erection (erectile dysfunction)
• Loss of appetite

Typically the benefits of antidepressants outweigh the possible side effects. Which antidepressant is best for you depends on a number of issues, such as your symptoms and any other health conditions you may have.

Ask your doctor and pharmacist about the most common possible side effects for your specific SNRI and read the patient medication guide that comes with the prescription.

Safety issues

SNRIs are safe for most people. However, in some circumstances they can cause problems. For example:

• Venlafaxine, desvenlafaxine and levomilnacipran may raise your blood pressure.
• Duloxetine may worsen liver problems.

Other issues to discuss with your doctor before you take an SNRI include:

• Drug interactions. Tell your doctor about any other prescription or over-the-counter medications, herbs or other supplements you’re taking. Some antidepressants can cause dangerous reactions when combined with certain medications or herbal products. For example, SNRIs may increase your risk of bleeding, especially when you’re taking other medications that also increase the risk of bleeding, such as ibuprofen (Advil, Motrin IB, others), aspirin, warfarin (Coumadin, Jantoven) and other blood thinners.
• Serotonin syndrome. Rarely, serotonin syndrome can occur when you take antidepressants that can cause levels of serotonin to increase in your body. This most often occurs when two medications that raise serotonin are combined, such as other antidepressants, certain pain or headache medications, or St. John’s wort.
  • Signs and 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.
  • Seek immediate medical attention if you have any of these symptoms.
• Antidepressants and pregnancy. Talk with your doctor about the risks and benefits of specific antidepressants. Some antidepressants may harm your baby if you take them during pregnancy or while you’re breast-feeding. If you’re taking an antidepressant and considering getting pregnant, talk to your doctor about the possible risks. Don’t stop taking your medication without contacting your doctor first, as stopping might pose risks for you.

Suicide risk and antidepressants

Most antidepressants are generally safe, but the FDA requires that all antidepressants carry black box warnings, the strictest warnings for prescriptions. In some cases, children, teenagers and young adults under 25 may have an increase in suicidal thoughts or behavior when taking antidepressants, especially in the first few weeks after starting or when the dose is changed.

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, immediately contact your doctor or get emergency help.

Keep in mind that antidepressants are more likely to reduce suicide risk in the long run by improving mood.

Stopping treatment with SNRIs

SNRIs are not considered addictive. However, stopping antidepressant treatment abruptly or missing several doses may cause withdrawal-like symptoms. This is sometimes called discontinuation syndrome. Withdrawal-like symptoms may be more likely to occur with venlafaxine or desvenlafaxine, though they can occur when any SNRI is stopped abruptly. Work with your doctor to gradually and safely decrease your dose.

Withdrawal-like symptoms can include:

• Dizziness
• Headache
• Flu-like symptoms, such as tiredness, chills and muscle aches
• Irritability or agitation
• Nausea
• Insomnia or sleep disturbances, such as nightmares
• Diarrhea

Finding the right antidepressant

People may react differently to the same antidepressant. For example, a particular drug may work better — or not as well — for you than for another person. Or you may have more, or fewer, side effects from taking a specific antidepressant than someone else does.

Inherited traits play a role in how antidepressants affect you. In some cases, where available, results of special blood tests may offer clues about how your body may respond to a particular antidepressant. However, other variables besides genetics can affect your response to medication.

When choosing an antidepressant, your doctor takes into account your symptoms, any health problems, other medications you take and what has worked for you in the past.

Typically, it may take several weeks or longer before an antidepressant is fully effective and for initial side effects to ease up. Your doctor may recommend dose adjustments or different antidepressants, but with patience, you and your doctor can find a medication that works well for you.