SNRIs vs. SSRIs: What Is the Difference?

Clinical depression is one of the most common forms of mental illness, with an estimated 19.4 million people, or 7.8 percent of all US adults, affected by one or more depressive episodes in 2019.

If you’ve been diagnosed with depression, your healthcare provider may prescribe medication called an antidepressant to reduce the severity of your symptoms and help you gain additional control over your mental health.

Two of the most common types of antidepressants prescribed to treat depression are selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).

SSRIs and SNRIs are both effective at treating depression (and for some drugs, certain types of anxiety too). 

However, there are a few differences between SSRIs and SNRIs that you should be aware of if you’re considering either type of medication.

Below, we’ve explained how SSRIs and SNRIs work to treat depression and anxiety, as well as the major differences between these two similar types of antidepressants. 

Selective serotonin reuptake inhibitors, or SSRIs, are antidepressants that work by inhibiting the reuptake of the neurotransmitter serotonin, thereby increasing serotonin levels. 

SSRIs are commonly used as first-line treatments for major depressive disorder (MDD), as well as anxiety disorders such as generalized anxiety disorder (GAD), social anxiety disorder, panic disorder and post-traumatic stress disorder. 

As treatments for depression, SSRIs work by increasing the levels of serotonin in your brain and body. 

Serotonin is a neurotransmitter that’s responsible for managing certain aspects of your feelings, moods and thoughts. It’s involved in regulating happiness and anxiety. Serotonin also plays an important role in stimulating the parts of your brain that control sleep and waking.

Low levels of serotonin are associated with depression, anxiety, obsessive-compulsive disorder and suicidal behavior.

Evidence suggests that by increasing serotonin, SSRIs can make depression, anxiety and other mental health disorders less severe.

SSRIs first came onto the market in the late 1980s, with fluoxetine (Prozac®) receiving approval from the FDA in 1987. Compared to older antidepressants, SSRIs have a lower risk of causing side effects and drug interactions.

Today, SSRIs are used by tens of millions of people and are typically the first type of medication mental health professionals turn to when dealing with depression.

Popular SSRIs used to treat depression and anxiety include citalopram (Celexa®), escitalopram (Lexapro®), fluoxetine (Prozac), fluvoxamine (Luvox®), paroxetine (Paxil®), sertraline (Zoloft®) and vilazodone (Viibryd®). 

Serotonin-norepinephrine reuptake inhibitors, or SNRIs, are a class of antidepressants that also work by inhibiting the reuptake of serotonin. However, they also target another neurotransmitter, called norepinephrine.

Norepinephrine, or noradrenaline, is a neurotransmitter that’s involved in several aspects of your mental and physical health.

In the brain, norepinephrine is involved in regulating your sleep-wake cycle, helping you to wake up in the morning, allowing you to focus on specific tasks and assisting in the creation and retrieval of memories. It also plays an important role in certain feelings, including anxiety.

Additionally, norepinephrine is involved in stimulating your cardiovascular system, helping you to maintain a healthy heart rate and blood pressure. It creates usable energy for your body by breaking down fat and increasing blood sugar.

Norepinephrine is also involved in your body’s fight or flight response, which helps you to quickly take action in stressful, potentially dangerous situations.

Low levels of norepinephrine are associated with problems such as poor concentration, lethargy and attention deficit hyperactivity disorder (ADHD). They may also contribute to depression.

By targeting both serotonin and norepinephrine, SNRIs may help to treat mental disorders such as depression and anxiety.

The first SNRIs came onto the market in 1993, when the FDA approved venlafaxine (originally sold as Effexor®) as a treatment for major depressive disorder. 

Today, millions of people regularly use SNRI medications to treat depression and other mental health conditions, including generalized anxiety disorder, panic disorder, social anxiety disorder and more.

In addition to depression and anxiety, some SNRIs are also approved by the FDA as treatments for fibromyalgia and diabetic peripheral neuropathy.

SNRIs used to treat depression, anxiety or  other conditions include venlafaxine (Effexor XR®), duloxetine (Cymbalta®), desvenlafaxine (Pristiq®), milnacipran (Savella®) and levomilnacipran (Fetzima®). 

When it comes to clinical depression, there’s no “perfect” drug for everyone. In fact, it’s common to try several antidepressants — including different types of antidepressants — before finding one that works well for you.

SSRIs and SNRIs are both commonly used as first-line treatments for depression, meaning they are the medications that healthcare providers generally prescribe first when treating people with clinical depression.

Compared to older antidepressants, both SSRIs and SNRIs are generally safer, with fewer side effects and potential interactions than drugs such as monoamine oxidase inhibitors (MAOIs) or tricyclic antidepressants (TCAs).

When it comes to effectiveness, most studies show that SSRIs and SNRIs are both effective at reducing the severity of major depression and preventing relapse. 

In one meta-analysis involving 15 studies and more than 3,000 participants, researchers found that SSRIs resulted in remission (the reduction or disappearance of symptoms) in 41.9 percent of people with depression, compared to 48.5 percent of people treated with SNRIs.

However, the same meta-analysis noted that people were slightly more likely to drop out of the study if they were given an SNRI. Overall, the researchers found that the small differences in remission rate weren’t clinically significant.

In general, research suggests that SSRIs and SNRIs are similar in terms of effectiveness, albeit with some differences that may make one type of antidepressant more suitable for some people than the other.

Remember that depression can vary significantly from person to person, both in terms of someone’s specific symptoms of depression and the severity of their symptoms.

Because SSRIs and SNRIs work differently, your healthcare provider may recommend one type of medication over the other if they think it’s a better match for your symptoms and needs.

SSRIs and SNRIs can both cause side effects. Most of these are mild and transient, although a small percentage of people prescribed these medications might experience side effects that are persistent or severe. 

Common side effects of SSRIs include:

• Headaches

• Dizziness

• Sleep disturbances (difficulty sleeping or oversleeping)

• Changes in appetite and/or body weight

• Xerostomia (dry mouth)

• Anxiety

Some SSRIs may be more likely to cause side effects than others. If you’re prescribed an SSRI, you can check the drug labeling provided with your medication for a detailed list of potential side effects.

Common side effects of SNRIs include:

• Nausea

• Somnolence (sleepiness)

• Sweating

• Xerostomia (dry mouth)

• Loss of appetite

• Constipation

• Anorexia

Because of their effects on norepinephrine, SNRIs can produce a moderate increase in systolic and diastolic blood pressure levels.

Although precise rates of side effects can vary from drug to drug, some research suggests that side effects are more common — or more bothersome — with SNRIs than with SSRIs.

For example, a meta-analysis comparing SSRIs and SNRIs found that people who used SNRIs were more likely to drop out from research studies due to adverse effects than people who took SSRIs. However, the difference in drop-outs was small and not statistically significant.

Both SSRIs and SNRIs can cause sexual adverse effects, including erectile dsyfunction (ED), a reduced level of sexual desire and difficulty reaching orgasm.

If you’re prescribed an SSRI or SNRI and start to experience side effects, don’t stop taking your medication. Instead, let your healthcare provider know about how you’re feeling.

To reduce the severity of side effects, your healthcare provider may recommend adjusting your dosage, switching to a different type of antidepressant or using a second medication (known as adjunct therapy) in addition to your antidepressant. 

Make sure to closely follow your healthcare provider’s instructions and let them know if you get any side effects that are severe, persistent or concerning.

Our full guide to antidepressant side effects discusses these issues and steps you can take to deal with them in more detail. 

Because of their effects on serotonin levels, both SSRIs and SNRIs can cause drug interactions when used with other medications that increase serotonin. 

One serious, potentially life-threatening drug interaction involving SSRIs and SNRIs is serotonin syndrome, which develops when serotonin levels become dangerously high.

Symptoms of serotonin syndrome include a rapid heart rate, high body temperature, increase in blood pressure levels, shivering, tremor, sweating, dilation of the pupils, involuntary movements and overactive reflexes.

To avoid drug interactions, make sure to inform your healthcare provider about all medications, supplements and other substances you currently take or have recently taken before using any SSRI or SNRI medications. 

Although SSRIs and SNRIs are some of the most common antidepressants on the market, they aren’t the only antidepressant medications available.

If you have a depressive disorder or other mental health disorder, your healthcare provider may also consider one of the following types of antidepressants:

• Tricyclic antidepressants (TCAs). These older antidepressants are equally as effective as SSRIs, but have a higher risk of causing side effects. TCAs generally aren’t used as first-line depression treatments, but are used off-label for issues such as chronic pain.
  

• Monoamine oxidase inhibitors (MAOIs). Another older class of antidepressants, MAOI medications are rarely used today due to their significant risk of causing side effects and interactions. However, they may be used if other medications aren’t effective.
  

• Atypical antidepressants. Some antidepressants don’t fit into obvious classes of drugs and are referred to as “atypical” medications. These may be used when other drugs are ineffective at treating depression or cause unwanted effects. 

If you’ve been diagnosed with depression or an anxiety disorder, your healthcare provider may recommend using an SSRI or SNRI to reduce the severity of your symptoms.

When it comes to treating depression symptoms, SSRIs and SNRIs are both effective for most people. Your healthcare provider will choose the most appropriate medication for you based on your needs, symptoms and medical history.

Make sure to use your medication as prescribed and inform your healthcare provider if you get any side effects or don’t feel any improvement in your depression symptoms. 

We offer several FDA-approved SSRIs and SNRIs online via our online psychiatry service, with medication available following a consultation with a licensed psychiatry provider.

Worried you might have depression? Our guide to the signs of clinical depression explains what to look for if you’re feeling depressed, as well as the steps you can take to access expert help.