SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors)

SNRIs (serotonin and norepinephrine reuptake inhibitors) are a class of antidepressants that work by changing the activity of serotonin and norepinephrine. These are chemicals that can affect your mood, as well as many other bodily and mental functions.

These medications are often used to treat conditions like depression, anxiety and chronic pain.

Types of SNRI medications

There are different types of SNRIs available in the United States. These include:

• Desvenlafaxine (Khedezla™, Pristiq®)
• Duloxetine (Cymbalta®, Drizalma®)
• Levomilnacipran (Fetzima®)
• Milnacipran (Savella®)
• Venlafaxine (Effexor®)

What conditions does an SNRI manage?

The U.S. Food and Drug Administration (FDA) has approved different SNRIs for the following conditions:

• Chronic pain (duloxetine)
• Diabetes-related neuropathy (duloxetine)
• Fibromyalgia (milnacipran, duloxetine)
• Generalized anxiety disorder (duloxetine, venlafaxine)
• Major depressive disorder (desvenlafaxine, duloxetine, levomilnacipran, venlafaxine)
• Panic disorder (venlafaxine)
• Social anxiety disorder (venlafaxine)

Healthcare providers sometimes prescribe these medications for other conditions, too. This is an “off-label” use. Examples include:

• Attention-deficit/hyperactivity disorder (ADHD)
• Symptoms linked to menopause
• Migraines
• Obsessive-compulsive disorder (OCD)
• Peripheral neuropathy from chemotherapy
• Urinary incontinence

How do SNRIs work?

Serotonin and norepinephrine are neurotransmitters. These are molecules that dictate how different regions of your brain talk to each other. Normally, after neurotransmitters deliver their message, your brain cells reabsorb them. This is a process called reuptake. SNRIs block the reabsorption of serotonin and norepinephrine, allowing them to remain active in your brain for a longer period of time.

Serotonin and norepinephrine play a role in the regulation of:

• Appetite
• Memory
• Mood
• Libido
• Sleep
• Social behavior
• Focus
• Energy

What are the potential benefits of an SNRI?

These medications help manage symptoms of many mental health conditions, as well as certain physical health conditions. These medications often work well when paired with therapy. SNRIs are usually well tolerated, with mild or minimal side effects.

SNRI side effects

Common side effects may include:

• Digestive issues
• Dizziness
• Dry mouth
• Excessive sweating
• Headache
• High blood pressure
• Sexual dysfunction
• Sleep disturbances
• Weight gain

Each medication has different side effects. Ask your provider or pharmacist for more information about each type.

Risks or complications

While these medications are generally safe, they may cause rare but serious complications in some cases:

• Antidepressant discontinuation syndrome: Stopping your medication too quickly may lead to symptoms like dizziness, flu-like aches or anxiety. Always talk to your provider before making dosage changes.
• QT prolongation: A problem with your heart’s electrical system causes it to take too long to reset between beats. If untreated, it could be life-threatening.
• Serotonin syndrome: This is when too much serotonin builds up in your body. Warning signs include confusion, a fast heart rate, fever and/or stiff muscles. Contact your doctor or go to the nearest ER if you have these symptoms.
• Suicidal thoughts: People under 25 may be at higher risk of experiencing suicidal thoughts.

If you’re thinking about suicide, you can reach out for help. Let your provider know. You can also call or text 988 (U.S.) to reach the Suicide and Crisis Lifeline. Someone is available to talk to you 24/7.

What interacts with SNRIs?

Some medications may interact with SNRIs, including:

• Blood clot-preventing medication (low-dose aspirin, clopidogrel)
• Herbal supplements (St. John’s wort)
• Certain migraine medicines (triptans)
• NSAIDs (ibuprofen, diclofenac, naproxen)
• Over-the-counter cough suppressants (like dextromethorphan)
• Other antidepressants

This isn’t a complete list. Talk to your healthcare provider about all the medications and supplements you currently take. They’ll let you know if an SNRI is the safest option to manage your symptoms.

If you need surgery while taking an SNRI, tell your surgeon. These medications may change your blood pressure while you’re asleep and under anesthesia. Your provider may need to adjust your dose before the procedure. Never change or stop your medication unless your provider says it’s safe.

Can I drink alcohol while on an SNRI?

It’s best to avoid alcohol while taking antidepressants, including SNRIs. Alcohol is a depressant and might interfere with how well the medication works. It can sometimes make depression symptoms worse. If you have concerns about drinking, talk to your provider.

Can I take SNRIs if I’m pregnant or thinking of becoming pregnant?

SNRIs may also pose risks during pregnancy. Some studies show they can affect a developing fetus. But stopping treatment suddenly can be harmful, too, as untreated depression or anxiety may worsen. If you’re pregnant or planning to become pregnant, talk with your provider. They’ll go over the possible risks and benefits and help you choose the safest option.

Stopping treatment with SNRIs

If you need or want to stop taking an SNRI, your provider will help you gradually reduce your dose. Quitting abruptly can lead to a group of symptoms known as antidepressant discontinuation syndrome. These symptoms typically happen if you’ve been on the medication for six weeks or longer.

How long does it take for an SNRI to work?

SNRIs take time to work. Most people start to notice benefits after four to six weeks at the right dose. For some, it may take nine to 12 weeks. If you don’t feel better by then, check in with your provider. They may suggest adjusting your treatment plan.