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SSRI vs SNRI: Differences, Similarities, and How They Work

7 min.

SSRIs and SNRIs are both commonly prescribed antidepressants, but read on to learn more about key similarities and differences between the medications.

By: Dr. Eli Muhrer, M.D.

March 7, 2024


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While therapy is essential for treating mental health conditions, it’s not always enough to help someone feel their best—which is where medication comes in. Two of the most commonly used kinds of medication are selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs). Simply put, these antidepressants alter brain chemistry to help relieve symptoms of common mental health conditions, such as depression and anxiety.

If your mental healthcare provider has suggested an antidepressant medication as a part of your treatment plan, you might be wondering what SSRIs or SNRIs are and how they work.  Read on for a comprehensive guide to the similarities and differences between the medications, their uses, side effects, and more. 

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As mentioned, SSRIs and SNRIs are medications that target brain chemicals to help people feel better. “We all have naturally occurring chemicals in our bodies, including neurotransmitters, which are chemicals in our brain related to depression and anxiety, among other things,” says Claire Streeter, PMHNP, ARNP, a Charlie Health Psychiatric Mental Health Nurse Practitioner. Common neurotransmitters include serotonin, norepinephrine, and dopamine.

Since these brain chemicals are thought to play a role in mental health conditions, medications like SSRIs or SNRIs that target one or more neurotransmitters can help alleviate symptoms of depression, anxiety disorders, or other conditions. Before diving into the key differences between SSRIs and SNRIs, it’s important to understand what each one is and how each works. 

What is an SSRI?

As the name suggests, a selective serotonin reuptake inhibitor is an antidepressant that will inhibit the reuptake of serotonin, which essentially means increasing the amount of serotonin available in the brain between neurons. An imbalance or deficiency of serotonin is believed to contribute to conditions like depression and anxiety (a widely accepted theory known as the serotonergic hypothesis or serotonin hypothesis). In line with this theory, SSRIs work to counteract this. 

“An SSRI helps capture those larger waves of symptoms,” says Charlie Health Psychiatric Mental Health Nurse Practitioner Rebecca Holland, PMHNP-BC, adding that the medications can help improve symptoms related to depression, anxiety, panic, and more. Although the name only mentions serotonin, Holland says SSRIs also have a “downstream impact” on other neurotransmitters in the brain since they work together. Examples of SSRIs and their most common brand names are escitalopram (Lexapro), fluoxetine (Prozac), and sertraline (Zoloft).

What is an SNRI?

A serotonin and norepinephrine reuptake inhibitor is an antidepressant that will target not only serotonin in the brain but also another neurotransmitter, norepinephrine, Streeter explains. In short, SNRIs inhibit the reuptake of both serotonin and norepinephrine. This means SNRIs increase the levels of serotonin and norepinephrine in the brain, going a step further than SSRIs to address anxiety and depression symptoms. 

Similar to SSRIs, SNRIs may have a downstream effect on other neurotransmitters. Streeter notes that there’s evidence to suggest that SNRIs indirectly impact dopamine, which can also help improve symptoms. Examples of SNRIs and their most common brand names are duloxetine (Cymbalta), venlafaxine (Effexor), and desvenlafaxine (Pristiq).

Selective serotonin reuptake inhibitor (SSRI)

Serotonin and norepinephrine reuptake inhibitor (SNRI)

    • Increases serotonin levels in the brain

    • Used to treat conditions like depression, anxiety, OCD, and PTSD

    • Examples include escitalopram (Lexapro), fluoxetine (Prozac), and sertraline (Zoloft)

  • Increases serotonin and norepinephrine levels in the brain
  • Used to treat depression, anxiety, chronic pain, and fibromyalgia
  • Examples include duloxetine (Cymbalta), venlafaxine (Effexor), and desvenlafaxine (Pristiq)

Similarities between SSRIs and SNRIs

Now that you understand how SSRIs and SNRIs work, we can compare them. To start, here are a few of the major similarities between the two kinds of medication.

Both target neurotransmitters

As mentioned, both classes of medications work by targeting chemicals in the brain known as neurotransmitters. SSRIs affect serotonin, and SNRIs affect serotonin and norepinephrine. Both SSRIs and SNRIs may have indirect effects on other neurotransmitters.

Both help treat anxiety and depression

The Food and Drug Administration approves SSRIs and (most) SNRIs to treat anxiety disorders and major depressive disorder. Both also have plenty of other approved uses. Someone with an eating disorder, post-traumatic stress disorder (PTSD), or obsessive-compulsive disorder (OCD) may be prescribed one of the antidepressants.

Both take at least a few weeks to improve symptoms

These medications don’t show noticeable results as soon as you take them. In fact, Streeter says it can take six to eight weeks to see the full impact of a specific dosage of antidepressant. Additionally, it’s common to start on a low dose and gradually increase it. You may not experience the best results until you reach your optimal therapeutic dose. The ideal dose is different for everyone. 

Both may cause side effects

It’s important to note that both SSRIs and SNRIs can result in bothersome side effects such as nausea, headaches, change in appetite, and more, says Streeter. Typically, the side effects are temporary. 

Differences between SSRIs and SNRIs

When comparing an SSRI and SNRI, it’s also helpful to consider the differences. Some major differences between the medications are as follows. 

SSRIs are usually prescribed first

SSRIs are a “first line” treatment, meaning an SSRI is often the first type of medication a psychiatrist will prescribe to someone with depression or an anxiety disorder, says Streeter. This is due to the evidence we have about their efficacy and safety. If someone doesn’t respond well to an SSRI or two, then they might be prescribed an SNRI.

SNRIs are also indicated for pain

SNRIs have a unique characteristic: they can help with chronic pain. For this reason, Holland says that someone with a chronic pain disorder such as fibromyalgia co-occurring with a mental health condition could benefit from a serotonin and norepinephrine reuptake inhibitor –– and in this case, it could be the first-line treatment for them. 

When to use an SSRI or SNRI 

When it comes down to it, everyone’s different. Your provider, typically a psychiatrist or psychiatric nurse practitioner, will assess your symptoms and make a decision on whether you should take an SSRI or an SNRI and, from there, which specific antidepressant medication you should take and what dosage. 

A provider’s decision of whether to prescribe an SSRI or an SNRI medication is never one-size-fits-all. They will complete a thorough evaluation of your history and symptoms. They’ll have to consider co-occurring conditions (both mental health and physical health), potential side effects, and drug interactions if you take any other prescriptions. You can rest assured that your provider has undergone extensive training and is looking out for your best interest when determining your treatment plan.

Additionally, you should never change your medication dose or stop taking it on your own without direction or supervision from a healthcare provider. This can result in withdrawal symptoms and potential danger. 

SSRI and SNRI side effects

As briefly mentioned before, SSRIs and SNRIs both have the possibility of adverse effects. “These medicines can help with mental health symptoms because they work in the brain, but they don’t just work in the brain,” says Streeter. “These chemicals are throughout your body and can unintentionally end up putting you at increased risk for issues elsewhere.” 

There are many potential adverse effects, and everyone’s body responds differently to medications. However, Holland says the most common side effects of SSRIs are typically gastrointestinal, such as upset stomach or nausea, and the most common side effects of SNRIs are neurological, such as headaches. The side effects are broad, and there’s a lot of overlap between the medications, including changes in appetite and weight, sleep issues, sexual dysfunction, and more. 

The side effects are most likely to occur at the beginning of taking the antidepressant and usually lessen as time goes on and your body adjusts, Streeter says. Also, they are not permanent, meaning if you stop the medication, the side effects will go away as the medication leaves your body. Additionally, your healthcare provider will start you on a lower dose to result in fewer side effects. If you’re taking an SSRI or SNRI medication and you’re experiencing side effects, don’t hesitate to tell your provider. They can help you figure out a plan to make you feel more comfortable.

Additionally, one major (but rare) increased risk when taking an SSRI or SNRI is serotonin syndrome. This occurs when your serotonin level is dangerously high, and it is a medical emergency. Signs of serotonin syndrome include agitation, dilated (large) pupils, high blood pressure, confusion, and more. In severe instances of serotonin syndrome, people may experience fever and seizures. Seek immediate medical attention if you’re experiencing any of these symptoms after taking an SSRI or SNRI.

Another major (but rare) side effect that these medications carry is increased suicidal thinking, which is marked as a warning on the medication itself (known as a black box warning issued by the FDA). This side effect is more common in young people, and even among them, it is very rare. Typically, it occurs when a person already has these types of thoughts when starting the medication or when there is a dose change—it rarely occurs after a person has been taking a consistent dose for weeks to months. Though uncommon, this is why it is important to be in close contact with your provider whenever starting or changing an SSRI or SNRI.

A woman in a black sweater sits in a session with a psychiatrist deciding whether or not to start an SSRI or SNRI.

Medication management at Charlie Health

If you or a loved one are struggling with an anxiety disorder or severe depression and could benefit from therapy and medication management, Charlie Health is here to help. Charlie Health’s virtual Intensive Outpatient Program (IOP) provides more than once-weekly mental health treatment for young people and families dealing with complex mental health conditions, including major depressive disorder, anxiety disorder, and more. 

Our expert clinicians incorporate evidence-based therapies into individual counseling, family therapy, and group sessions. We also offer medication management to clients as needed.  With this kind of holistic treatment, managing your mental health is possible. Fill out the form below or give us a call to start healing today. 

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