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SSRIs, SNRIs, and SSNRIs, Oh My! How do they work?


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In the ever-growing world of pharmaceuticals, it can be difficult and confusing to choose which medication is right for you. SSRIs, SNRIs, and SSNRIs are effective treatment options for everything from major depression to chronic nerve pain. You’ve probably heard all of the names for these medications (Prozac, Cymbalta, Zoloft, etc) but what’s the difference?

Selective Serotonin Reuptake Inhibitor (SSRI)

Common names:  Citalopram (Celexa), Escitalopram (Lexapro), Fluoxetine (Prozac), Sertraline (Zoloft)

How it works: SSRIs target the inhibitory neurotransmitter, Serotonin. Serotonin is important for promoting good moods. Serotonin in the brain is released from a presynaptic nerve into the synapse. Receptor sites on the postsynaptic nerve use what serotonin they can, while remaining serotonin in the synapse is transported back to the presynaptic nerve via the serotonin transporter, SERT. Simply put, SSRIs block this reabsorption of serotonin to the presynaptic nerve so that more serotonin is left within the synapse for use.

Serotonin Norepinephrine Reuptake Inhibitor (SNRI)

Common names: Desvenlafaxine (Pristiq), Venlafaxine (Effexor), Duloxetine (Cymbalta)

How it works: SNRIs work similarly to an SSRI, however, they also inhibit the reabsorption of norepinephrine. Norepinephrine is important for cognitive function, alertness, motivation, and energy, which are all necessary for healthy social relationships. As social dysfunction is a typical characteristic in depressed patients, inadequate norepinephrine is potentially to blame.[i] SNRIs allow more norepinephrine and serotonin to remain in the synapse for use to promote good moods and healthy social encounters.

Selective Serotonin Norepinephrine Reuptake Inhibitor (SSNRI)

Common names: Milnacipran (Savella)

How it works: This particular class of SNRIs has been approved for treatment of fibromyalgia, rather than depression. Fibromyalgia is commonly associated with chronic widespread pain through increased nociceptive sensitivity. Serotonin and norepinephrine both play roles in pain mediation by regulating these nociceptive pathways. The word selective in this classification indicates that this pharmaceutical is more selective for norepinephrine than serotonin, but still has reabsorption affects on both.[ii]

While SSRIs, SNRIs, and SSNRIs have proven beneficial over the years, patients who take them are not immune from side effects, including dizziness, sexual dysfunction, nausea, insomnia, and others.[iii] Additionally, using these medications over time can deplete neurotransmitter stores.[iv][v] More and more people have turned to complementary and alternative medicine as a way to manage their depression and related disorders. Rhodiola rosea, Saffron, Omega-3 fatty acids, 5-HTP, L-tyrosine, and Inositol are just a few of the many natural remedies that have been studied.[vi] Replenishing neurotransmitters levels, especially serotonin and norepinephrine, is a great place to start in treating diseases such as depression and fibromyalgia by ensuring sufficient amounts are available for use by the brain.

*IMPORTANT NOTICE: Prescribed medications, especially SSRIs, SNRIs, and SSNRIs, should never be discontinued without talking with your practitioner.



[i] Moret, C., & Briley, M. (2011, May 31). The importance of norepinephrine in depression. Neuropsychiatr Dis Treat, 7(1), 9-13.
[ii] English, C., PharmD, Rey, J. A., PharmD, BCPP, & Rufin, C., PharmD Candidate. (2010, May). Milnacipran (Savella), a Treatment Option for Fibromyalgia. Pharmacy and Therapeutics, 35(5), 261-266.
[iii] Qaseem, A., MD, PhD, MHA, Snow, V., MD, Denberg, T. D., MD, PhD, Forciea, M., MD, & Owens, D. K., MD, MS. (2008, November 18). Using Second-Generation Antidepressants to Treat Depressive Disorders: A Clinical Practice Guideline from the American College of Physicians. Ann Intern Med, 149(10), 725-733.
[iv] Bosker, F. J., Tanke, M. A., Jongsma, M. E., Cremers, T. I., Jagtman, E., Pietersen, C. Y., . . . Den Boer, J. A. (2010, December). Biochemical and behavioral effects of long-term citalopram administration and discontinuation in rats: Role of serotonin synthesis [Abstract]. Neurochemistry International, 57(8), 948-957.
[v] Siesser, W. B., Sachs, B. D., Ramsey, A. J., Sotnikova, T. D., Beaulieu, J., Zhang, X., . . . Gainetdinov, R. R. (2013, January 16). Chronic SSRI Treatment Exacerbates Serotonin Deficiency in Humanized Tph2 Mutant Mice. ACS Chem Neurosci, 4(1), 84-88.
[vi] Qureshi, N. A., & Al-Bedah, A. M. (2013, May 14). Mood disorders and complementary and alternative medicine: A literature review. Neuropsychiatr Dis Treat, 9, 639-658.


Clinical Contributor

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Connie Shoemaker, ND

Connie Shoemaker, ND

“Educating Sanesco’s clients is the culmination of a life’s work.” Beginning when she left the hospital environment to manage a functional laboratory, Genova Diagnostics (formerly Great Smokies Laboratories) in 1987, Dr. Connie Shoemaker has continued to increase her knowledge of herbs and biochemistry as a journey of love. With her bachelor’s in science from Western Carolina University, she had worked in hospital laboratories for the first twelve years of her career. Then, personal health challenges led her to discover a new approach to her health and a determination to share it with others. In 1991, she began teaching and educating innovative practitioners in the U.S. and internationally as a manager of marketing, sales, and customer service.

The addition of her Doctor of Naturopathy degree to her existing knowledge base expanded her knowledge and her respect for a more natural approach to healing through balance. At Sanesco, she initially served to oversee technical development of products and services.

Now, she educates Sanesco’s clients on application of the CSM™ model for their specific patients and how to integrate the CSM™ model with other modalities they offer in their practice. In her personal life, Connie educates private clients on various health topics.

Disclaimer: The information provided is only intended to be general educational information to the public. It does not constitute medical advice. If you have specific questions about any medical matter or if you are suffering from any medical condition, you should consult your doctor or other professional healthcare provider.

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