Antidepressant SNRIs help relieve depression symptoms, such as irritability and sadness. Here's how they work and what side effects they may cause. By Mayo Clinic Staff

Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a class of medications that are effective at easing depression symptoms. SNRIs are also sometimes used to treat other conditions such as anxiety and nerve pain.

Serotonin (ser-o-TOE-nin) and norepinephrine (nor-ep-ih-NEF-rin) reuptake inhibitors ease depression by affecting chemical messengers (neurotransmitters) used to communicate between brain cells. Like most antidepressants, SNRIs work by changing the levels of one or more of these naturally occurring brain chemicals.

SNRIs block the absorption (reuptake) of the neurotransmitters serotonin and norepinephrine in the brain. They also affect certain other neurotransmitters. Changing the balance of these chemicals seems to help brain cells send and receive messages, which in turn boosts mood. Medications in this group of antidepressants are sometimes called dual-action antidepressants.

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

  • Duloxetine (Cymbalta)
  • Venlafaxine (Effexor XR)
  • Desvenlafaxine (Pristiq)

All SNRIs work in a similar way and generally cause similar side effects. However, each SNRI varies in chemical makeup, so one may affect you differently than another does. Side effects are usually mild and go away after the first few weeks of treatment. Taking your medication with food may decrease nausea.

The most common side effects of SNRIs include:

  • Nausea
  • Dry mouth
  • Dizziness
  • Excessive sweating

Other side effects may include:

  • Tiredness
  • Difficulty urinating
  • Agitation or anxiety
  • Constipation
  • Insomnia
  • Sexual problems, such as reduced sexual desire, difficulty reaching orgasm, or the inability to maintain an erection (erectile dysfunction)
  • Headache
  • Loss of appetite

Read the package insert for additional side effects and talk to your doctor or pharmacist if you have questions.

Here are some issues to think about before taking an SNRI:

  • Antidepressants and pregnancy. Some antidepressants may harm your child if you take them during pregnancy or while you're breast-feeding. If you're taking an antidepressant and you're considering getting pregnant, talk to your doctor or mental health provider about the possible dangers. Don't stop taking your medication without contacting your doctor first.
  • Drug interactions. When taking an antidepressant, be sure to tell your doctor about any other medications or dietary supplements you're taking. Some antidepressants can cause dangerous reactions when combined with certain medications or herbal products.
  • Venlafaxine, desvenlafaxine and blood pressure. At higher doses, venlafaxine or desvenlafaxine may raise your blood pressure. Your doctor may want to check your blood pressure regularly if you already have high blood pressure.
  • Duloxetine and liver problems. Duloxetine may worsen liver problems. If you have liver problems and are taking duloxetine, your doctor may need to do periodic blood tests to see how well your liver is working.
  • Serotonin syndrome. Rarely, an SNRI can cause dangerously high levels of serotonin. This is known as serotonin syndrome. It most often occurs when two medications that raise serotonin are combined. These include other antidepressants, certain pain or headache medications, and the herbal supplement St. John's wort. Signs and symptoms of serotonin syndrome include anxiety, agitation, sweating, confusion, tremors, restlessness, lack of coordination and rapid heart rate. Seek immediate medical attention if you have any of these signs or symptoms.
  • Upper gastrointestinal (GI) bleeding. Venlafaxine may increase the risk of upper GI bleeding. The use of aspirin, ibuprofen (Advil, Motrin IB, others) and naproxen sodium (Aleve, others), or anticoagulants, such as warfarin (Coumadin), while taking SNRIs may increase your risk of bleeding.

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.

SNRIs aren't 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 are more common with venlafaxine. Work with your doctor to gradually and safely decrease your dose.

Withdrawal-like symptoms can include:

  • Dizziness
  • Flu-like symptoms, such as tiredness, chills and muscle aches
  • Anxiety
  • Urinary urgency
  • Diarrhea

SNRIs may be a good choice if you have depression that hasn't improved with other medications or if you have chronic pain in addition to depression.

Each person reacts differently to a particular antidepressant and may be more susceptible to certain side effects. Because of this, one antidepressant may work better for you than another, or they may be used in combination. When choosing an antidepressant, your doctor will take into account your symptoms, what health problems you have, what other medications you take and what has worked for you in the past.

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. The study of how genes affect a person's response to drugs is called pharmacogenomics. However, other variables besides genetics can affect your response to medication.

Typically, it may take several weeks or longer before an antidepressant is fully effective and for initial side effects to ease up. You may need to try several antidepressants before you find the right one, but hang in there. With patience, you and your doctor can find a medication that works well for you.

June 26, 2013