Serotonin Norepinephrine Reuptake Inhibitor (SNRI)

What SNRIs Are and What They Do

What are SNRIs?

Every year, 6.7% of the U.S. population will be diagnosed with depression. There is not one specific cause of depression, and treatment methods are not an exact, concrete science. But fortunately, there are many different, effective methods for alleviating depression symptoms. Most patients will respond favorably to a combination of medications and talk therapy.

Research supports the benefits of adding talk therapy or counseling to depression medication treatment, as a review of studies in this area shows that a combination of therapy and medication is significantly more effective for treating depression when compared to medication alone. Medication can treat some of the chemical imbalances associated with depression, whereas therapy can help patients to work through feelings of sadness, hopelessness, or guilt and develop healthier patterns of thinking.

There are many different types of depression medications, and each one will affect patients differently. While one may work for Patient A, Patient B may not respond. It is common for depression patients to try a few different medications before finding one that works for them.

One of the most popular medications is SNRIs or serotonin-norepinephrine reuptake inhibitors. The following article will explain how and why SNRIs work, and who can most benefit from taking an SNRI. If SNRIs and other depression medications don’t work, the article will also explain alternative treatment methods for treatment-resistant depression.

How do SNRIs work?

Depression can be caused by a combination of factors, including genetics, environmental triggers, and brain chemistry. Talk therapy is focused on coping with the environmental aspects of depression and there is no way to change a person’s genetics. Medications, however, can help patients whose depression is rooted in issues with brain chemistry.

SNRI drugs, just like any medication, do not work for everyone, but they are a promising treatment option for those who can take medication and prefer this treatment method. That being said, a review of 15 different studies found that 48.5 percent of patients achieved remission with SNRI drugs, meaning that these medications tend to work for about half of people who take them.

Suppose you have depression that does not respond to other treatments. In that case, SNRI medications may be a suitable option, but keep in mind that research also shows that when compared to the popular SSRI drugs, SNRIs are slightly more likely to create side effects that cause people to stop taking them. If other depression medications do not work for you, you may still be able to tolerate the side effects of SNRI drugs if they alleviate your depression symptoms. 

Alternative treatment options, like TMS, can be explored for patients who do not respond to SNRI drugs or other antidepressants. Some people may also need alternatives to medication because the side effects of the medication may be intolerable or even dangerous. 

In their brain, there are naturally occurring neurochemicals that transmit important signals throughout the nerve synapses. Some of these signals control the feelings of mood, well-being, alertness, cognition, and energy. When these neurochemicals are not present, depression symptoms can arise. SNRIs, and other popular depression medicines, manipulate these chemicals.

What are the brain chemicals that play a role in depression symptoms?

  • Serotonin
  • Dopamine
  • Norepinephrine

SNRIs are used to block the brain’s ability to reabsorb serotonin and norepinephrine. In depressed patients, the brain either produces too little of these chemicals or reabsorbs them too quickly. Either way, there aren’t enough neurotransmitters circulating in the brain to help regulate mood and energy. SNRIs block the brain’s ability to reabsorb these chemicals too quickly. Thus, more vital and beneficial neurotransmitters are left circulating in the brain.

SNRIs, like other depression medicines, can take several weeks to work. It takes time for the brain to produce enough neurochemicals for the patient to feel a noticeable reduction in depression symptoms. SNRIs are particularly effective for depression patients who also suffer from chronic nerve pain. The most common SNRIs on the market with FDA approval are the following:

  • Pristiq, Khedezla
  • Cymbalta
  • Fetzima
  • Effexor XR

Effexor XR is also used to treat panic disorder and anxiety.


SNRIs are often compared to SSRIs, which are a popular class of antidepressant drugs. In fact, antidepressant prescribing trends show that sertraline and fluoxetine, two SSRI drugs, have been the most widely prescribed antidepressants over time. SSRI drugs inhibit the reuptake of serotonin only, which is how they exert their antidepressant effect. They achieve this by increasing the availability of serotonin in the nervous system, whereas SNRIs, as their name suggests, increase the availability of both serotonin and norepinephrine. 

If you’re wondering, “How is SNRI better than SSRI?” the answer lies in the ability of SNRI drugs to increase both serotonin and norepinephrine levels, allowing SNRIs to treat numerous symptoms of depression. Since SNRIs seem to treat a wide variety of depression symptoms, they may be more effective than SSRIs for some patients. Research shows that compared to those who take an SSRI drug, those who take SNRIs for depression are more likely to experience remission. SNRIs may be particularly useful for those with treatment-resistant depression or for patients who do not respond favorably to other antidepressant drugs.

Do SNRIs always work?

No, unfortunately. SNRIs are not a panacea for depression. Every patient is different, and a lot of depression sufferers will need to try a few medications to find the right one for them. But, some people may not be able to take an SNRI or any depression medication for that matter. These patients with treatment-resistant depression can find relief with deep brain stimulation techniques, in combination with therapy.

Why should someone avoid SNRIs?

SNRIs can cause some serious side effects that can be dangerous for patients. For example, SNRIs may raise blood pressure, or worsen liver problems. Patients with high blood pressure or a liver condition should not take an SNRI. SNRIs can also interact poorly with other popular medications, including aspirin or warfarin for blood clots.

In very rare cases, some patients cannot handle any extra serotonin increases in the body. These patients can have a fatal reaction to SNRIs and other medicines that interact with serotonin, called serotonin syndrome.

SNRIs are also not recommended for pregnant or nursing mothers. For patients who take an SNRI and become pregnant, their doctor may recommend weaning them off an SNRI and trying an alternative medication that is safe for babies.

Children, teenagers, and young adults under age 25 can experience an increased risk of suicide after taking SNRIs. This risk will dissipate within a few weeks after taking the medicine. Overall, taking an SNRI will lower the risk of suicide.

What are effective alternatives to SNRIs and other classes of depression medication?

Deep brain stimulation techniques are promising and useful depression medication alternatives. Electroconvulsive therapy and transcranial magnetic stimulation can be highly effective for depression patients who cannot take SNRIs.

However, ECT comes with a host of side effects, including short-term memory problems. ECT also requires anesthesia and is considered minor surgery. Patients need a recovery time after each session of ECT. Also, ECT is not a targeted treatment option. A small, short seizure is induced in the brain, so all parts of the brain are affected. For some patients, the side effects and invasiveness of ECT may be unpleasant.

TMS has fewer side effects, minimal recovery time, and is also a more targeted option in the treatment of depression. TMS uses a powerful magnetic coil to stimulate specific areas of the brain. TMS treatment is effective in up to 70% of all cases. The most common side effect is a mild headache, and patients are not put under any anesthetic. TMS treatment sessions typically last between 40 and 60 minutes. Patients can return to work or school shortly after treatment, and can even safely drive after a session.

Who can benefit from TMS treatment?

TMS is a useful alternative treatment option for the following types of depression patients:

  • Patients with treatment-resistant depression
  • Patients who are at high risk of suicide and need fast relief from depression symptoms
  • Patients who do not respond well to ECT
  • Patients who don’t want to try ECT or medication

However, TMS is not recommended for patients who have any type of metal filings in their heads or necks, not including braces or dental implants.

Although depression is a serious and lifelong condition, it can be effectively managed with SNRIs or deep brain stimulation techniques in combination with talk therapy. If you or someone you care about is suffering from depression, please reach out to a mental health counselor today to explore your depression treatment options.

If you are ready to explore TMS as a treatment option for depression, contact Pulse TMS today. Your TMS treatment will begin with a consultation with a licensed psychiatrist, who will create a plan that best meets your individual needs. If TMS is a suitable fit for you, you will receive daily treatment for 6-8 weeks on a schedule that works for you. You may participate in therapy alongside TMS treatment, and after you complete TMS, we will recommend ongoing activities, such as meditation and healthy sleep habits to help you maintain the benefits of TMS.

Updated 5/30/21