Serotonin and norepinephrine reuptake inhibitors (SNRIs)

SNRIs are a class of medications that are effective at easing depression symptoms. SNRIs are also sometimes used to treat other mental health conditions such as anxiety.

How serotonin and norepinephrine reuptake inhibitors work

Serotonin and norepinephrine reuptake inhibitors (SNRIs) ease depression by affecting chemical messengers (neurotransmitters) used to communicate between brain cells. Most antidepressants work by changing the levels of one or more of these naturally occurring brain chemicals.

SNRIs block the absorption (reuptake) of the neurotransmitters serotonin (ser-oh-TOE-nin) and norepinephrine (nor-ep-ih-NEF-rin) 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 reuptake inhibitors.

Serotonin and norepinephrine reuptake inhibitors approved to treat depression

SNRIs approved by the Food and Drug Administration to treat depression, with their generic names followed by brand names in parentheses, include:

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

As with some other antidepressants, venlafaxine is available in an immediate-release form that requires two or three doses a day and in an extended-release (XR) form that allows you to take it just once a day.

Sometimes, SNRIs are used to treat conditions other than depression.

Side effects and cautions

All SNRIs work in a similar way and generally cause similar side effects. However, each SNRI has a different chemical makeup, so one may affect you differently than does another.

Side effects of SNRIs can include:

• Nausea (particularly with duloxetine)
• Dry mouth
• Dizziness
• Insomnia
• Sleepiness
• Constipation
• Increased blood pressure (with venlafaxine)
• Excessive sweating
• Reduced sexual desire or difficulty reaching orgasm
• Inability to maintain an erection (erectile dysfunction)
• Increased heart rate
• Heart palpitation
• Difficulty urinating
• Tremor
• Headache
• Agitation or anxiety
• Changes in appetite
• Abnormal vision, such as blurred vision or double vision
• Muscle weakness

Nausea is less common with the extended-release form of SNRIs.

Safety concerns

Here are some things 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 remedies.
• Venlafaxine and blood pressure. At high doses, venlafaxine may raise your blood pressure. Your doctor may want to check your blood pressure regularly if you already have high blood pressure. Your doctor may also recommend that you take a prescription medication to lower your blood pressure, such as a beta blocker.
• Blood thinning medications and SNRIs. Use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) or anticoagulants, such as warfarin (Coumadin), while taking SNRIs may increase your risk of bleeding.
• 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, medications for certain health conditions and the herbal supplement St. John's wort. Signs and symptoms of serotonin syndrome include confusion, rapid or irregular heart rate, dilated pupils, fever and unconsciousness. Seek immediate medical attention if you have any of these signs or symptoms.

Suicide risk and antidepressants

The Food and Drug Administration (FDA) requires that all antidepressants carry a warning that some children, adolescents and young adults may be at increased risk of suicide when taking antidepressants. Anyone taking an antidepressant should be watched closely for worsening depression or unusual behavior — especially in the first few weeks after starting an antidepressant. Keep in mind, antidepressants are more likely to reduce suicide risk in the long run by improving mood.

Stopping treatment with serotonin and norepinephrine reuptake inhibitors

SNRIs aren't considered addictive. However, stopping treatment abruptly or missing several doses can cause withdrawal-like symptoms, including:

• Nausea
• Headache
• Dizziness
• Lethargy
• Flu-like symptoms

This is sometimes called discontinuation syndrome. Talk to your doctor before stopping so that you can gradually taper off the medication.

Finding the right antidepressant

One SNRI may work better for you than another. For example, venlafaxine may be a good choice if you have depression that hasn't improved with other medications (treatment-resistant depression). Duloxetine may help ease chronic pain in addition to treating depression.

Each person reacts differently to a particular antidepressant and may be more susceptible to certain side effects. When choosing an antidepressant, your doctor will take into account your particular symptoms, what health problems you have, what other medications you take and what has worked for you in the past. Sometimes a combination of antidepressants may be the best treatment choice.

Inherited traits play a role in how antidepressants affect you. In some cases, DNA tests such as cytochrome P450 (CYP450) tests may give clues as to whether an antidepressant is likely to ease symptoms or cause side effects. DNA testing isn't widely used yet but is becoming more common.

It can take a long time to find the best treatment for depression. It takes 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.

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