SSRI and SNRI drugs are both used to treat depression, but they function differently. SNRI drugs may be more effective, but they tend to produce more side effects.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are used to treat depression. While both medications are antidepressants, there are some key differences between SSRI vs. SNRI drugs.

Article at a Glance:

  • Both SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin-norepinephrine reuptake inhibitors) are antidepressant medications.
  • SSRIs work by increasing serotonin levels in the brain and relieving symptoms of depression.
  • SNRIs increase both serotonin and norepinephrine in the brain to fight depression, especially when a person doesn’t respond to SSRIs.
  • The Norepinephrine affected by SNRIs is connected to motivation, socialization and intelligence.
  • A medical professional can help you determine whether a SSRI or SNRI is best for your needs.

How do Reuptake Inhibitors Work?

If you’re considering taking an SSRI or SNRI medication for depression, you might be wondering, “How do reuptake inhibitors work?” These drugs work by blocking the reabsorption of certain brain chemicals called neurotransmitters, making more of them available for transmitting messages in the brain. Reuptake inhibitors increase levels of neurotransmitters associated with emotions.

How SSRIs Work

According to medical experts, SSRI drugs work by blocking the reuptake of the neurotransmitter serotonin, which increases serotonin levels in the brain over time, thereby relieving symptoms of depression. SSRI drugs are typically the first line of treatment for depression. A doctor may prescribe an SSRI after reviewing symptoms and making a depression diagnosis.

Common SSRIs

There are a variety of SSRI drugs available, and some may work better than others for certain people. A doctor can help determine which SSRI is the best choice for a particular individual. The National Institute of Mental Health reports the following SSRI list:

  • Fluoxetine
  • Sertraline
  • Citalopram
  • Paroxetine
  • Escitalopram

How SNRIs Work

SNRI drugs treat depressive symptoms by preventing the reuptake of both serotonin and norepinephrine, which increases levels of both neurotransmitters in the brain. Increased availability of these neurotransmitters can improve mood and fight off symptoms of depression. SNRI drugs are an option for people who do not respond to SSRIs.

Common SNRIs

Much like SSRIs, a doctor can decide which medication will work best for the patient. Some medications may work differently than others so it’s important for patients to speak with their doctor about any concerns they have. Common SNRI medications include the following:

  • Effexor
  • Cymbalta
  • Pristiq
  • Savella
  • Fetzima

Difference in Neurotransmitters

To understand the effects of SSRIs and SNRIs on depressive symptoms, it is important to know the different types of neurotransmitters and their functions and more specifically the differences between serotonin vs. norepinephrine.

According to scientists from the University of Texas Health Science Center in San Antonio, serotonin is a neurotransmitter involved in emotions, appetite, motor skills, and cognitive functioning. Experts report that norepinephrine plays a role in depression because it is involved with motivation, intelligence and socialization.

Side Effects Comparison

While SSRIs and SNRIs provide relief of depressive symptoms, they can also produce side effects. Not everyone will experience the same side effects. Doctors prescribe medications because they believe the benefits will outweigh any unwanted effects. The U.S. Food and Drug Administration (FDA) provides a comparison of SNRI vs SSRI side effects to help people understand the key differences.

Side Effects of SSRIs

Common SSRI side effects can include any of the following:

  • Nausea
  • Tremors
  • Nervous feelings
  • Sleep disturbances
  • Sexual dysfunction

Gastrointestinal complaints, anxiety, agitation, sexual issues, sleep disturbances, and weight gain are also common unwanted effects of SSRI medications. Citalopram tends to demonstrate the fewest side effects, whereas paroxetine and fluvoxamine are the most poorly tolerated.

Side Effects of SNRIs

The FDA reports the following SNRI side effects:

  • Sleep disturbances
  • Drowsiness
  • Dizziness
  • Anxiety or nervousness
  • Constipation or diarrhea
  • Nausea/vomiting
  • Sweating
  • Dry mouth
  • Fatigue
  • Headache

Adverse reactions that lead to discontinuation of treatment are more common with SNRIs when compared to SSRIs, so it is possible that side effects may be more troublesome with SNRI drugs.

Which One is Best for Me?

The best medicine to treat depression varies from person to person. SNRIs tend to be more effective than SSRIs, but some people will find that SSRIs are more effective for them. A physician or psychiatrist can discuss your health history and symptoms to determine whether an SSRI or SNRI is best for you. He or she will also evaluate potential side effects to determine which medication can be expected to provide the most benefit with the fewest unwanted effects. It is possible that you may have to try a few medications before finding the one that is most beneficial for you.

Key Points: SSRIs vs. SNRIs

A comparison of SSRIs vs. SNRIs is helpful for anyone who may need medication for depression. As discussed, the following are true of these types of medications:

  • SSRIs inhibit the reuptake of serotonin, whereas SNRIs inhibit both serotonin and norepinephrine reuptake
  • Both SSRIs and SNRIs increase levels of neurotransmitters
  • Serotonin is involved in emotions, appetite, motor skills, and cognitive functioning
  • Norepinephrine is implicated in motivation, intelligence and socialization
  • Both SSRI and SNRI drugs can produce side effects such as sleep disturbances, fatigue, nausea, nervousness, weight gain and sexual dysfunction, but side effects may be more severe with SNRIs
  • SNRIs may be slightly more effective than SSRIs, according to the research, but the best medication will vary from person to person

If you or a loved one live with addiction and a co-occurring mental health disorder like depression, contact The Recovery Village to speak with a representative about how our treatment programs and online therapy can work for you.

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Editor – Thomas Christiansen
With over a decade of content experience, Tom produces and edits research articles, news and blog posts produced for Advanced Recovery Systems. Read more
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Medically Reviewed By – Jenni Jacobsen, LSW
Dr. Jenni Jacobsen is a licensed social worker through the Ohio Counselor, Social Worker and Marriage and Family Therapist Board. She has over seven years working in the social work field, working with clients with addiction-related and mental health diagnoses. Read more

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National Institute of Mental Health. “Mental health medications.” October 2016. Accessed May 12, 2019.

Sansone, R., & Sansone, L. “Serotonin norepinephrine reuptake inhibi[…]cal comparison.” Innovations in Clinical Neuroscience, April 2014. Accessed May 13, 2019.

Frazer, A., & Hensler, J. ”Serotonin involvement in physiological f[…]nction and behavior.” U.S National Library of Medicine, 1999. Accessed May 13, 2019.

Moret, C., & Briley. M. “The importance of norepinephrine in depression.” Neuropsychiatric Disease and Treatment, May 31, 2011. Accessed May 13, 2019.

U.S. Food & Drug Administration. “Depression- Medicines to help you.” January 19, 2018. Accessed May 13, 2019.

Ferguson, J. “SSRI antidepressant medications: Ad[…]ts and tolerability.” The Primary Care Companion to the Journal of Clinical Psychiatry, February 2001. Accessed May 13, 2019.

Machado, M., & Einarson, T. “Comparison of SSRIs and SNRIs in major depressive disorder: A meta‐analysis of head‐to‐head randomized clinical trials.” Journal of Clinical Pharmacy and Therapeutics, March 5, 2010. Accessed May 13, 2019.



Medical Disclaimer

The Recovery Village aims to improve the quality of life for people struggling with substance use or mental health disorder with fact-based content about the nature of behavioral health conditions, treatment options and their related outcomes. We publish material that is researched, cited, edited and reviewed by licensed medical professionals. The information we provide is not intended to be a substitute for professional medical advice, diagnosis or treatment. It should not be used in place of the advice of your physician or other qualified healthcare providers.