Norepinephrine's Role in Treating Mood Problems

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Norepinephrine, also known as noradrenaline, is both a hormone and a brain neurotransmitter or chemical. Research suggests that norepinephrine Norepinephrine plays a role in mood, attention, and stress. Research also suggests that low norepinephrine levels in the brain can play a role in causing depression and other mood problems.

At a Glance

Norepinephrine plays an important part in how your body responds to stress, but it can also have a significant effect on your mood. When levels of this chemical are too low, you may experience symptoms of depression or other mood problems. Keep reading to look more about the effects of norepinephrine and how serotonin and norepinephrine reuptake inhibitors (SNRIs) can help relieve mood symptoms associated with low norepinephrine levels.

What Is Norephinephrine?

Norepinephrine is 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.

What Does Norepinephrine Do?

Norepinephrine plays a role in attention and the body's fight or flight response. When faced with a stressful situation, the chemicals are released, and the body enters a heightened state of readiness.

Hormones, including noradrenaline, cortisol, and adrenaline, are released, setting off a chain reaction in the body that prepares the individual to either flee or face the threat. Heart rate, blood pressure, and respiration increase.

In addition to its role in the fight-or-flight response, norepinephrine also has a crucial role in regulating mood and arousal levels.

Low levels of this chemical have been linked to symptoms such as reduced mood, decreased motivation, poor concentration, and low energy levels. Because of this, medications that help increase norepinephrine levels in the brain are often used to help alleviate symptoms of depression.

Conditions Affected by Norepinephrine

Norephinephrine has been linked to several health conditions. The impact can vary depending on whether the levels are too high or too low. 

Low levels of norepinephrine are associated with conditions such as:

On the other hand, high levels of norepinephrine may lead to problems such as anxiety, manic episodes in bipolar disorder, high blood pressure, irregular heartbeat, headaches, and nervousness.

SNRIs for Mood Disorders

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.

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.

Other medications that are used to modify norepinephrine activity include norepinephrine antagonists, beta-blockers, and amphetamines.

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

Types of Norepinephrine Medications

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. According to some sources, Savella works by inhibiting the reabsorption of both serotonin and norepinephrine equally and may even favor norepinephrine.

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.

How to Increase Norephinephrine Levels

Norepinephrine is a major part of the body's natural response to stress. Effective stress management helps keep norepinephrine levels in balance. 

If you have a mild case of low norepinephrine levels, there are lifestyle changes you can make that may help increase the amount of this brain chemical in your body. Strategies that can help include:

  • Getting regular exercise
  • Eating a balanced diet
  • Getting enough sleep
  • Engaging in activities that bring you happiness

If you are experiencing symptoms of a mental health condition like depression, anxiety, or other problems, it is important to talk to your doctor. Medications can help rebalance your norepinephrine levels and improve your symptoms.

Keep in Mind

Depression can have many causes, but things like chronic stress and trauma can play a part in causing hormone and neurotransmitter imbalances. Taking steps to address these problems on your own can help, but medications that increase chemicals like norepinephrine and serotonin can also help. Talk to your doctor about which treatments might be the most helpful for you.

If you or a loved one are struggling with depression, contact the Substance Abuse and Mental Health Services Administration (SAMHSA) National Helpline at 1-800-662-4357 for information on support and treatment facilities in your area.

For more mental health resources, see our National Helpline Database.

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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.
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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.