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If you or a loved one suffers from depression, it’s helpful to know about serotonin and norepinephrine reuptake inhibitors (SNRIs). These antidepressants emerged in the mid 1990s, and are often a next step for people who don’t have much success with selective serotonin reuptake inhibitors (SSRIs); they work on a similar principle, but SNRIs affect two brain chemicals—serotonin and norepinephrine—while SSRIs affect only the first one.

Your psychiatrist can advise you on whether SNRIs are worth exploring. Treatment generally requires some trial and error to arrive at what works best for each individual, providing maximum relief with minimal side effects. A medication like SNRIs is just one tool, and if it’s right for you or your loved one, it should be used in conjunction with other treatment strategies, such as positive lifestyle changes and one or more types of therapy.

What Conditions Do SNRIs Treat?

Serotonin and norepinephrine reuptake inhibitors are prescribed to treat the most common symptoms of moderate to severe cases of clinical depression. They are also sometimes used to treat generalized anxiety and certain anxiety disorders, panic disorder, bipolar depression, fibromyalgia, chronic pain (especially nerve pain), and some other conditions.

How Do SNRIs Help?

Serotonin and norepinephrine are neurotransmitters, or brain chemicals that send messages between cells. Serotonin is sometimes called “the feel good chemical” because it elevates your mood and helps control anxiety, and it helps regulate sleep, appetite, and other bodily functions. Norepinephrine plays a role in the regulation of emotions, thought processes, concentration, memory, and more.

Low levels of these neurotransmitters are seen in people with depression and anxiety conditions. SNRIs inhibit cells’ reuptake of these chemicals to increase the levels present; the medication does not boost their production.

What Types of SNRIs Are Available?

The different SNRIs on the market are generally believed to work in the same way. However, there are differences in how much each one affects reuptake of each of the two brain chemicals, and there can be some variance in their side effects. Be sure your prescribing doctor knows about all the medications and supplements you take, and all your health conditions.

There are four serotonin and norepinephrine reuptake inhibitors approved by the FDA for treating depression:

  • Desvenlafaxine (Pristiq)
  • Duloxetine (Cymbalta)
  • Levomilnacipran (Fetzima)
  • Venlafaxine (Effexor XR)

Duloxetine is also FDA approved for treating anxiety and certain types of chronic pain; venlafaxine is also FDA approved for treating some anxiety disorders and panic disorder.

Milnacipran (Savella) is another SNRI, available only as a brand name product, approved by the FDA for treating fibromyalgia. It is used in some other countries outside the US for treatment of depression, and is sometimes prescribed for off-label use in the US to treat this condition.

What Side Effects can SNRIs Cause?

All medications can cause side effects, and they vary from person to person, as does the severity and duration. All SNRIs are generally considered to have the same potential side effects, but that doesn’t necessarily mean you will react to each one the same way.

Usually, the benefits of SNRIs outweigh the side effects. If you experience side effects, talk to your prescribing doctor about adjusting your dosage or, if necessary, trying other treatment alternatives.

The most common side effects of serotonin and norepinephrine reuptake inhibitors include:

  • Nausea
  • Increased or decreased appetite (and associated weight gain or loss)
  • Dry mouth
  • Dizziness
  • Headache
  • Excessive sweating
  • Muscle weakness
  • Fatigue
  • Heart palpitations or increased heart rate
  • Constipation
  • Difficulty falling or staying sleeping
  • Sexual dysfunction (e.g., decreased sex drive, difficulty reaching orgasm, erectile dysfunction)

What Are Other Possible Concerns when Taking SNRIs?

In addition to side effects, there are other potential concerns when taking serotonin and norepinephrine reuptake inhibitors. These can include:

  • Allergic reactions
  • Increased suicidal thoughts/risk of suicide
  • Dangerous interactions with other drugs or supplements
  • Elevated blood pressure
  • Worsening liver problems
  • Increased risk of bleeding (especially concerning if you take other drugs or supplements that increase this risk, like aspirin or other NSAIDs, anticoagulants or blood thinners, ginkgo biloba, ginseng, St. John’s wort, etc.)
  • Harm to the fetus or infant if you’re pregnant or breastfeeding
  • Withdrawal symptoms if you abruptly stop taking an SNRI or miss several doses (however, SNRIs are not considered addictive)
  • Serotonin syndrome (an excess of serotonin, which becomes more likely if you combine an SNRI with another drug or supplement that increases serotonin levels); symptoms include anxiety, agitation, restlessness, perspiring, high fever, confusion, tremors, loss of coordination, changes in blood pressure, and rapid heart rate; seek emergency medical attention if you suspect you or your loved one is experiencing this rare complication

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