Norepinephrine's Role in Treating Mood Problems

Woman researching medicine on a cell phone
-Oxford-/ GettyImages

Norepinephrine, also known as noradrenaline, is both a hormone and a brain neurotransmitter, or chemical. It's mainly stored in the neurons (nerve cells) of the sympathetic nervous system with small amounts also stored in adrenal tissue, which lay on top of your kidneys.

As a hormone, norepinephrine is released into the bloodstream by the adrenal glands and works alongside adrenaline (also known as epinephrine) to give the body sudden energy in times of stress, known as the "fight or flight" response.

As a neurotransmitter, norepinephrine passes nerve impulses from one neuron to the next.


Medications that inhibit the reuptake of norepinephrine and serotonin (which is another neurotransmitter) are called serotonin-norepinephrine reuptake inhibitors (SNRIs). By inhibiting the reuptake of these two neurotransmitters, SNRIs essentially increase the levels of norepinephrine and serotonin in the brain. Serotonin helps regulate mood, anxiety, and other functions and norepinephrine helps mobilize the brain for action and can improve energy and attentiveness.

SNRIs have been found to be effective in treating mood disorders like depression, aspects of bipolar disorder, and anxiety disorders. SNRIs are also sometimes prescribed for chronic pain and fibromyalgia.

SNRIs for Mood Disorders

The SNRIs approved for use in major depression include Cymbalta (duloxetine), Effexor (venlafaxine), Fetzima (levomilnacipran), and Pristiq (desvenlafaxine), but there are others approved for other illnesses as well.

No antidepressants, including SNRIs, have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of bipolar disorder. However, they are sometimes prescribed as part of an individual treatment plan.

Common Side Effects

SNRIs may increase a person's blood pressure, particularly at higher doses, so your doctor may want to monitor your blood pressure if he prescribes one.

Side effects of SNRIs often go away after a couple of weeks, but if they don't or they are particularly bothersome, be sure to contact your doctor. Some common side effects of SNRIs include:

  • Anxiety
  • Constipation
  • Difficulty urinating
  • Dizziness
  • Dry mouth
  • Fatigue
  • Feeling drowsy
  • Headache
  • Losing your appetite
  • Nausea and vomiting
  • Sexual difficulties
  • Sweating more than usual


Each of these SNRIs is a little bit chemically different from the others.

Effexor (Venlafaxine)

Effexor was the first SNRI to be approved in the United States in 1993. It has been approved by the FDA for depression, panic disorder, social phobia, and generalized anxiety disorder (GAD). Effexor inhibits the reabsorption of serotonin quite a bit more than it does norepinephrine.

Cymbalta (Duloxetine)

In 2004, Cymbalta was the second SNRI to be approved in the United States. Because of the way it works, it has the highest number of FDA-approvals to treat illnesses, including diabetic peripheral neuropathy, depression, generalized anxiety disorder, fibromyalgia, osteoarthritis, and nerve pain. Like Effexor, Cymbalta also favors inhibiting the reabsorption of serotonin over norepinephrine, but to a lesser degree.

Pristiq and Khedezla (Desvenlafaxine)

Pristiq, the third SNRI to be approved, has only been approved to treat major depression so far. Khedezla is an extended-release tablet. Chemically, they work very similarly to Cymbalta. 

Savella (Milnacipran)

This is the fourth SNRI to be approved in the U.S. to treat fibromyalgia. Savella works by inhibiting the reabsorption of both serotonin and norepinephrine equally and may even favor norepinephrine, according to some sources.

Fetzima (Levomilnacipran)

The most recent member introduced to the SNRI family, Fetzima was approved by the FDA in 2013 and has also only been FDA-approved for treating depression. Fetzima inhibits norepinephrine reabsorption twice as much as serotonin reabsorption, making it unique among the SNRIs.

7 Sources
Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Mcintyre CK, Mcgaugh JL, Williams CL. Interacting brain systems modulate memory consolidation. Neurosci Biobehav Rev. 2012;36(7):1750-1762. doi:10.1016/j.neubiorev.2011.11.001

  2. Strawn JR, Geracioti L, Rajdev N, Clemenza K, Levine A. Pharmacotherapy for generalized anxiety disorder in adult and pediatric patients: an evidence-based treatment review. Expert Opin Pharmacother. 2018;19(10):1057–1070. doi:10.1080/14656566.2018.1491966

  3. Butler M, Urosevic S, Desai P, et al. Treatment for bipolar disorder in adults: a systematic review (Comparative Effectiveness Review, No. 208). Agency for Healthcare Research and Quality;2018. doi:10.23970/AHRQEPCCER208

  4. U.S. Food and Drug Administration. Depression medicines.

  5. Effexor [prescribing label]. U.S. Food and Drug Administration.

  6. Sansone RA, Sansone LA. Serotonin norepinephrine reuptake inhibitors: a pharmacological comparisonInnov Clin Neurosci. 2014;11(3-4):37–42.

  7. College of Psychiatric and Neurologic Pharmacists, National Alliance on Medical Illness. Desvenlafaxine (Pristiq).

Additional Reading

By Marcia Purse
Marcia Purse is a mental health writer and bipolar disorder advocate who brings strong research skills and personal experiences to her writing.