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SNRI Antidepressants: Their Side Effects, Uses, And MOA

SNRIs abuse

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SNRI antidepressants are one of the four main categories of depression medications. Standing for serotonin and norepinephrine reuptake inhibitor, SNRIs are a newer generation of medications. However, this does not mean that SNRI antidepressant medications are universally safe or better than other, older medicines.

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Learn About SNRIs:

What Are Serotonin And Norepinephrine Reuptake Inhibitors?

Serotonin and norepinephrine reuptake inhibitors, or SNRI antidepressants, are a relatively young class of antidepressants. The first medicine in this class, Effexor, was approved for use in 1993. These medications can improve mood by altering the chemistry in the brain, which is why they are classified as antidepressants.

The list of SNRI antidepressants with FDA approval is short. Just four medications currently have approval. They are:

  • Desvenlafaxine
  • Duloxetine
  • Levomilnacipran
  • Venlafaxine
As in the case with all antidepressant drugs, they should only be used under the supervision of a medical professional. If any signs of abuse are noticed, it is critical to find addiction treatment as soon as possible.

How Do SNRIs Work?

What antidepressants do to the brain is to increase the number of feel-good chemicals present. The differences between the classes of depression medications come down to how they alter the amount of chemicals present. Serotonin and norepinephrine reuptake inhibitors specifically impact serotonin and norepinephrine, as the name suggests.

Specifically, all types of SNRI antidepressants work by inhibiting the reuptake of serotonin and norepinephrine. This ensures that more of the chemicals are present in the brain at any given time. As a result, the user experiences elevated moods.

How long it takes for someone to feel the effects of these medications will vary. In general, it takes about four to six weeks from the start of treatment for the patient to feel changes.

woman uses SNRIs

Uses Of SNRIs

Serotonin–norepinephrine reuptake inhibitors were developed specifically to treat the major depressive disorder. However, they are also often used to alleviate moderate depression as well. As is the case with most antidepressants, there is the risk they will make the condition worse rather than better.

SNRI antidepressant medications are also used to treat other behavior disorders, including

  • anxiety
  • OCD
  • ADHD
  • PTSD
In some cases, these are off-label uses but have limited research to back up their applications.

Additionally, SNRI antidepressants can be used to treat pain and menopausal symptoms. For pain, they are specifically used to treat neuropathic pain and that caused by fibromyalgia. In many cases, these medications are used when both pain and depression are present. While some antidepressants are used for migraines, this is not a common application of serotonin and norepinephrine reuptake inhibitors. However, tricyclic antidepressants for pain, which can overlap with serotonin and norepinephrine reuptake inhibitors, are used on occasion for headaches.

man with headache after taking SNRIs

Side Effects Of SNRIs

Compared to some of the other depression medication classes, SNRI antidepressants have fewer side effects. However, this does not mean that users will not experience any. These medications are known to have adverse effects of use, some of which are tolerable and go away with time, and others tend to be less tolerable or even dangerous.

Among the side effects that can be experienced with most types of SNRI antidepressants are:

  • Nausea
  • Vomiting
  • Sexual dysfunction
  • Dry mouth
  • Dizziness
  • Headache
  • Excessive sweating
  • Tiredness
  • Constipation
  • Insomnia
  • Loss of appetite
  • Weight loss
  • Changes in sexual function, such as reduced sexual desire, difficulty reaching orgasm or the inability to maintain an erection (erectile dysfunction)
Most medications in this class are considered liver-friendly antidepressants. The exception to this is duloxetine, which can make liver impairment worse.

Contraindications And Warnings

There is a black box warning on SNRI antidepressants, as is the case with all prescription antidepressants. This is the strictest type of warning a prescription medication can carry. The greatest risk is during the first months on the medicine, and those under the age of 25 are the most susceptible. However, this is a risk to all serotonin and norepinephrine reuptake inhibitor users.

  • Venlafaxine, desvenlafaxine, and levomilnacipran all can raise blood pressure. Duloxetine should not be taken by anyone with liver disorders or impaired liver function.
  • SNRI drugs make it more difficult for the blood to clot. Other blood-thinning agents should be avoided while on these antidepressants.
  • Serotonin and norepinephrine reuptake inhibitors can interact with other antidepressants, various prescription medications, and supplements. There is a strong risk of serotonin syndrome occurring when combined with any other medication that increases the chemical in the body such as pain medications, other antidepressants that impact serotonin, and even supplements like St. John’s wort. Serotonin syndrome can be deadly.
  • Because SNRIs can decrease appetite, they are not meant to be used in the treatment of eating disorders except those that involve consistent overeating.
  • Some serotonin and norepinephrine reuptake inhibitors are on the list of safe antidepressants during pregnancy. However, not all are.
  • Finally, alcohol and all street drugs should be avoided throughout treatment. For some, this can be difficult, as many people self-medicate with various substances before seeking medical help with depression. However, things like weed and antidepressants are not a safe mix.

SNRIs Addiction And How To Cope With It

Despite the fact that SNRIs are not considered addictive, it is not surprising that SNRIs cause psychological addiction, like the rest of depression meds. Addiction to SNRIs is not only caused by abuse; a patient may take medications as prescribed and still get addicted to SNRIs. The matter is that a body gradually becomes tolerant to drugs, and patients may need to take a higher dose to experience the same result.

Addiction may also start manifesting when SNRIs are stopped. Stopping SNRI medications can be dangerous without proper supervision. Anyone who has problematic use or just wants to live without relying on medication can turn to drug rehabilitation facilities for assistance. It is possible to end dependence upon SNRI antidepressants.

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  1. Sansone RA, Sansone LA. Serotonin norepinephrine reuptake inhibitors: a pharmacological comparison. Innovations in Clinical Neuroscience. 2014; 11(3-4): 37–42.
  2. Shelton RC. Serotonin and Norepinephrine Reuptake Inhibitors. Handbook of Experimental Pharmacology. 2019; 250:145-180. doi: 10.1007/164_2018_164.
Sharon Levy

About Author

Sharon Levy, MD, MPH

After successful graduation from Boston University, MA, Sharon gained a Master’s degree in Public Health. Since then, Sharon devoted herself entirely to the medical niche. Sharon Levy is also a certified addiction recovery coach.


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