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Using SNRIs For Treating Depression

Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a group of drugs that are commonly used for treatment of depression (1). These medicines are also sometimes used to treat other conditions such as chronic pain, particularly nerve pain, and anxiety disorders (2). SNRIs are known to help alleviate the symptoms of depression by having an effect on the neurotransmitters that communicate between the brain cells. But how do they exactly work and are they truly effective in treating depression?

Using SNRIs For Treating Depression

Here, we take a look at using SNRIs for treating depression.

Overview of SNRIs

Serotonin-norepinephrine reuptake inhibitors, or SNRIs, are a group of drugs that work as antidepressants (1). They were first introduced in the mid-1990s and since then have been used effectively in the treatment of depression.

SNRIs are said to work on alleviating the symptoms of depression since they have an impact on two of the important neurotransmitters in the brain; norepinephrine and serotonin, which are believed to have a major role to play in depression patients (2). SNRIs are also known as dual acting antidepressants or dual reuptake inhibitors.

Other Than Depression, What Conditions Can SNRIs Treat?

While SNRIs are usually used for treating depression, they are also used for treating persistent pain, especially nerve pain and anxiety disorders. They are also used to treat the following conditions:

SNRIs are also a good form of treatment for those who have earlier experienced an unsuccessful treatment using SSRIs, or selective serotonin reuptake inhibitors. As compared to SNRIs, SSRIs only work on one neurotransmitter, that is, serotonin.

How Do SNRIs Work in Treating Depression?

Typically, people suffering from depression have been found to have low levels of norepinephrine and serotonin. These neurotransmitters or chemical messengers are responsible for controlling a person’s mood.

Norepinephrine is responsible for the levels of energy and alertness in the body, while serotonin, also referred to as the ‘feel good’ chemical, is associated with positive feelings and a feeling of overall wellbeing in the body.

SNRIs help treat depression by boosting the levels of these two neurotransmitters in the brain (3). These medications carry this out by preventing norepinephrine and serotonin from moving back into the cells that released them. Ultimately, SNRIs work by bringing about a change in the brain chemistry and improving the communication in between the brain nerve cell circuity that regulates a person’s mood.

What are the Different Types of SNRIs?

There are seven types of SNRIs that are currently available in the market and are used to treat depression. These include:

  • tramadol (brand name: Ultram)
  • atomoxetine (brand name: Strattera)
  • venlafaxine (brand name: Effexor XR)
  • milnacipran (brand name: Savella)
  • duloxetine (brand names: Cymbalta and Irenka)
  • desvenlafaxine (brand names: Khedezla and Pristiq)
  • levomilnacipran (brand name: Fetzima)

One more SNRI known as sibutramine (brand name Meridia) has been pulled from many countries in 2010, owing to the side effects of stroke and other cardiovascular events.

While milnacipran and levomilnacipran are available in the market only as branded drugs, the other SNRIs are available in both generic and branded formats.

Milnacipran is also used in the treatment of fibromyalgia and while the drug is not approved for treating depression by the US Food and Drug Administration (FDA), doctors nevertheless still prescribe it as an off-label medication for the purpose of treating depression. Off-label drugs are those that have been approved by the FDA for the treatment of one condition but is used for a treating a different condition as well that has not been approved. A doctor can still use the drug for treating other conditions, as the FDA does not regulate how doctors use the specific drug for treating patients.

Duloxetine and venlafaxine are also approved for the treatment of anxiety and panic disorder, while duloxetine is approved for treating chronic pain disorders and also anxiety disorders.

Side Effects Associated with SNRIs for Depression Treatment and Cautions

All of the seven SNRIs work in a similar manner and are known to cause similar side effects as well. However, some people may not experience any side effects, while some people may want to avoid taking these medications altogether.

The side effects of SNRIs are generally mild to moderate and disappear after using the drugs for a couple of weeks. When you take SNRIs with food, it helps reduce the side effect of nausea. If you are unable to tolerate a particular SNRI, your doctor may prescribe a different one for you, which you may be able to tolerate better. This is because each individual SNRI has a different chemical makeup.

Some of the most common side effects of SNRIs include: excessive sweating, nausea, headaches, muscle weakness, tremors, agitation, dizziness, dry mouth, fatigue, constipation, increased blood pressure, increased heart rate, palpitations, difficulty urinating, sleepiness, insomnia or changes in sleeping patterns, loss of appetite, fluid retention, especially in elderly people and changes in sexual function like decreased libido, difficulty in reaching an orgasm, or erectile dysfunction (4).

The benefits of these SNRI antidepressants far outweigh the side effects, which is why doctors prefer to begin treating depression with SNRIs. As mentioned above, there are, however, certain groups of people who should avoid taking SNRIs. These include:

Pregnant Women or Women Who Are Breastfeeding: Pregnant women or women who are breastfeeding should avoid taking SNRIs, as SNRIs pass into the breast milk and babies delivered to mothers who were taking SNRIs during their pregnancy often experience withdrawal symptoms such as tremors, feeding problems, and difficulty breathing. Pregnant women should only be prescribed SNRIs is the benefits of taking these medications outweigh the risk posed to both the mother and the child (5).

People Who Have High Blood Pressure Or Have Liver Damage: People who have liver problems or suffer from high blood pressure should also try to avoid taking SNRIs (5). This is because SNRIs can further increase their blood pressure (5). These medications also get processed in the liver and if you have existing liver problems, then the drug will tend to remain in the system much longer than it should, increasing the risk of side effects (5). If it is absolutely necessary to treat with SNRIs, then your doctor will keep a close eye on your liver function and blood pressure levels. Ultimately, though, all SNRIs tend to work similarly but have minor differences in their chemical makeup, which may also affect the side effects associated with each SNRI.

What Happens When You Stop SNRIs?

SNRIs are not addictive by nature, however, if you stop your antidepressant suddenly or end up missing many of the doses, then it may cause you to feel withdrawal symptoms. This phenomenon is also known as discontinuation syndrome (6). Such types of withdrawal-like symptoms are more commonly observed with venlafaxine and desvenlafaxine.

Towards the end of your treatment, your doctor will gradually and safely decrease your dose, until it’s time to stop the medications.

Some of the withdrawal-like symptoms of SNRIs may include: headache, dizziness, nausea; flu-like symptoms such as muscle aches, chills, and fatigue; agitation, irritability, mood swings and diarrhea (6).


SNRIs have proven to be an effective option for treating depression with anxiety or even tough-to-treat depression. If you have been diagnosed with depression, then you should discuss SNRIs as a treatment option with your doctor. If you are also currently undergoing treatment for depression, and you are not having any positive results with your present medication, then also you can discuss the option of taking SNRIs with your doctor.

Referral Links

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008300/
  2. https://www.ncbi.nlm.nih.gov/pubmed/20642317
  3. https://www.medicalnewstoday.com/kc/antidepressants-work-248320
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630974/
  5. https://www.healthline.com/health/depression/serotonin-norepinephrine-reuptake-inhibitors-snris#warnings
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449237/
Pramod Kerkar, M.D., FFARCSI, DA
Pramod Kerkar, M.D., FFARCSI, DA
Written, Edited or Reviewed By: Pramod Kerkar, M.D., FFARCSI, DA Pain Assist Inc. This article does not provide medical advice. See disclaimer
Last Modified On:October 15, 2019

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