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What are SNRIs?

Effexor, Cymbalta, and Pristiq are examples of SNRIs (serotonin-norepinephrine reuptake inhibitors). Learn more about this type of antidepressant and how SNRIs differ from SSRIs.

SNRIs list | What are SNRIs? | How they work | Uses | Types | Who can take SNRIs? | Safety | Side effects | Costs

Antidepressants are some of the most commonly prescribed medications in the United States and are essential treatments for people dealing with depression or other psychiatric disorders. Serotonin-norepinephrine reuptake inhibitors (SNRIs) are one class of antidepressant medications that treat major depressive disorder. Along with relieving the symptoms of depression, SNRIs are also used to treat other conditions such as anxiety disorders and chronic pain associated with diabetic neuropathy or fibromyalgia. SNRIs may be prescribed if you have a coexisting condition like neuropathic pain in addition to depression.

Continue reading to learn more about SNRIs and their uses, side effects, and safety information. The table below lists commonly used SNRIs and their costs.

List of SNRIs

Drug name Average cash price SingleCare savings Learn more
Effexor XR (venlafaxine) $582 per 30, 150 mg capsules Get Effexor XR coupons Effexor XR details
Cymbalta (duloxetine) $471 per 60, 20 mg capsules Get Cymbalta coupons Cymbalta details
Pristiq (desvenlafaxine) $525 per 30 tablets Get Pristiq coupons Pristiq details
Fetzima (levomilnacipran) $544 per 30, 80 mg capsules Get Fetzima coupons Fetzima details
Savella (milnacipran) $512 per 55 tablets, 4-week titration pack Get Savella coupons Savella details
Khedezla (desvenlafaxine) $223 per 30, 50 mg tablets Get desvenlafaxine ER coupons Desvenlafaxine ER details

What are SNRIs?

SNRIs are a class of drugs used to treat depression but have broader indications as well. Some SNRIs are approved by the Food and Drug Administration (FDA) for use in certain psychiatric disorders such as social anxiety disorder and panic disorder. Individuals with chronic nerve, muscle, or bone pain may also be prescribed an SNRI. 

SNRIs are similar to another class of antidepressants called selective serotonin reuptake inhibitors (SSRIs). Both types of medications work by affecting the levels of chemical messengers, known as neurotransmitters, in the brain. SSRIs and SNRIs both increase the neurotransmitter serotonin, but SNRIs have an additional pharmacological effect on another messenger called norepinephrine. Either type of antidepressant can be given as a first-line treatment for major depression, and SNRIs are sometimes tried if patients have not responded to therapy with SSRIs first.

How do SNRIs work?

SNRIs work by targeting neurotransmitters in the brain to regulate mood. Low levels of the neurotransmitters serotonin and norepinephrine are associated with depression and anxiety, and antidepressants like SNRIs can increase the amount of these chemicals. SNRIs block the reuptake of both serotonin and norepinephrine in the synapse or junction between neurons. The resulting increase in available neurotransmitters has been shown to relieve depression symptoms and improve energy. Some SNRIs also increase levels of dopamine, which plays a role in pleasure and motivation. 

Certain SNRIs have been proven to be effective for pain, which often overlaps with depression. Because chronic pain is also thought to be caused by a dysregulation of serotonin and norepinephrine, SNRIs are often used as a treatment for musculoskeletal or nerve pain that occurs with or without depression and anxiety.

What are SNRIs used for?

SNRIs are sometimes prescribed off-label to treat obsessive-compulsive disorder (OCD), hot flashes, and migraines, although these are not FDA-approved indications. 

RELATED: More medications that treat anxiety and depression

Who can take SNRIs?

Children and adolescents

All antidepressants, including SNRIs, have a black box warning issued by the FDA because they can potentially increase the risk of suicidal thoughts and behaviors in children, adolescents, and young adults up to 24 years old. Cymbalta (duloxetine) is the only SNRI that has an FDA-approved indication in this population for the treatment of generalized anxiety disorder in children older than 7 years old and fibromyalgia in adolescents older than 13 years old. Children who take SNRIs should consult with a mental health professional to monitor the potential risks and benefits of the medication.


SNRIs are effective in treating depression and other disorders like anxiety and pain in adults. Although SNRIs carry a black box warning for pediatric use, short-term studies of antidepressants did not show an increased risk of suicidality in adults older than 24 years old. 


SNRIs are generally safe and effective for use in older adults. Effexor XR (venlafaxine) and Cymbalta (duloxetine) are commonly prescribed in this population for the treatment of depression. However, side effects such as high blood pressure or hyponatremia (low blood sodium) may appear more often in seniors. Depending on the patient’s other health conditions, tolerability, and kidney or liver function, the dose may be lowered to reduce the incidence of adverse effects.

Are SNRIs safe?

SNRIs are generally safe when used as directed. In some circumstances, however, they have known safety risks. SNRIs have a black box warning about the potential increased risk of suicidal thoughts and behaviors in young patients. Patients who start taking SNRIs or other antidepressants should be monitored for signs of suicidality or any unusual changes in behavior. 

SNRIs are also associated with the following safety concerns:

  • Serotonin syndrome is a serious but rare side effect of SNRIs that occurs when levels of serotonin in the blood are too high. This toxicity is more likely to occur when SNRIs are taken with other over-the-counter or prescription medications that also increase serotonin, such as SSRIs, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants, atypical antidepressants, opioids, amphetamines, and triptans. Seek emergency medical care if you have symptoms of serotonin syndrome: severe nausea, dizziness, agitation, racing heartbeat, or fever.
  • SNRIs may increase blood pressure or heart rate. Patients who are at risk for hypertension or other cardiovascular conditions should monitor their blood pressure regularly during treatment. 
  • SNRIs may increase the risk of bleeding events, especially if taken with other drugs that affect platelet function such as nonsteroidal anti-inflammatory drugs (NSAIDs) or warfarin.
  • Hyponatremia, or low sodium levels, can occur during treatment with SNRIs. Older patients and those taking diuretics (water pills) are more at risk for this side effect, which may cause symptoms of headache, difficulty concentrating, confusion, and weakness.
  • Episodes of mania/hypomania, seizures, painful urination, high blood sugar, and angle-closure glaucoma have been reported in patients with preexisting risk factors for these side effects.

SNRI recalls

Meridia (sibutramine), an SNRI approved for weight loss, was withdrawn from the United States market in 2010 due to cardiovascular events and stroke associated with its use. 

SNRI restrictions

SNRIs should be restricted or used with caution in patients with the following conditions:

  • Significant hypertension or cardiac disease 
  • Bleeding disorder
  • Epilepsy
  • Bipolar disorder
  • Obstructive urinary disorder
  • Narrow-angle glaucoma
  • Diabetes
  • Kidney or liver problems 
  • Hypersensitivity or drug allergy to SNRIs

SNRI interactions

Certain medications should not be taken with SNRIs because their combined use can lead to harmful side effects. SNRIs taken together with other drugs that increase serotonin levels can cause serotonin syndrome, a serious and potentially fatal side effect. MAOIs in particular are contraindicated—or prohibited—in patients taking SNRIs and should be stopped at least two weeks before starting SNRI therapy. 

SNRIs may also increase the risk of bleeding when used concurrently with NSAIDs (such as ibuprofen, naproxen, or aspirin) or blood thinners like warfarin. 

Can you take SNRIs while pregnant or breastfeeding?

While SNRIs are sometimes used during pregnancy or while breastfeeding, there are risks associated with their use. Newborns whose mothers took antidepressants during the third trimester may experience temporary symptoms of withdrawal, including irritability, respiratory difficulty, and restlessness. However, untreated depression can also lead to a higher risk of negative outcomes during pregnancy. The risks and benefits of continuing SNRIs while pregnant or breastfeeding should be thoroughly discussed with a prenatal care provider. 

Stopping SNRIs

Stopping SNRIs abruptly can cause symptoms of withdrawal, known as discontinuation syndrome. Reported symptoms of discontinuation syndrome include:

  • Agitation
  • Anxiety
  • Dizziness
  • Nausea
  • Flu-like symptoms, such as fatigue
  • Sleep disturbances, such as insomnia

Discontinuation syndrome is most often seen with Effexor XR (venlafaxine) and is more likely to occur after a long duration of treatment with SNRIs. Withdrawal symptoms are temporary and usually last a few weeks. A gradual reduction in dose, rather than abruptly stopping the medication, is recommended to avoid discontinuation syndrome, and patients should be monitored by a healthcare provider to safely stop antidepressant treatment.

Are SNRIs controlled substances?

No, SNRIs are not controlled substances.

Common SNRI side effects

SNRIs have a similar mechanism of action and share many of the same side effects. Speak to your healthcare provider for medical advice about specific side effects and risks you might experience while taking SNRIs.

Common side effects of SNRIs include:

  • Nausea
  • Drowsiness
  • Dry mouth
  • Sweating
  • Loss of appetite
  • Constipation
  • Sexual dysfunction, such as decreased libido, abnormal ejaculation, and erectile dysfunction 
  • Fatigue
  • Headache
  • Insomnia
  • Anxiety
  • Vomiting
  • Increased heart rate
  • Palpitations

How much do SNRIs cost?

Prices of SNRIs can range between $200 and $600 without insurance. The cost of SNRIs varies depending on the type of medication, the strength, and whether the drug is a brand-name or generic version. Generic SNRIs are generally less expensive than their brand counterparts. Prices may also differ based on your insurance coverage. 

SingleCare offers free coupons to help lower the price of your medication. Speak with your healthcare provider and insurance company or use a free prescription discount card from SingleCare to find the best choice for you.