If you have a mental health condition like depression and are taking medication for it, it’s likely that you are taking either an SSRI or an SNRI. SSRIs are the most commonly prescribed antidepressants, with the SSRI sertraline (Zoloft) being the most commonly prescribed antidepressant overall. SNRIs are another extremely common type of drug. More than 48 million Americans took an antidepressant in 2019 alone, and the majority were prescribed an SNRI or SSRI. 

Although SSRIs and SNRIs are both commonly used to treat depression, there are some key differences between these medications. Learning more about each type of antidepressant and their differences can help guide you when discussing depression treatment with your doctor.

Antidepressants and Your Brain

When your brain produces neurotransmitters like serotonin or norepinephrine, they are often quickly taken back up by the neurons after being released so they do not linger too long in the brain. However, experts have long suspected that mental health conditions like depression and anxiety may occur because these neurotransmitters have lower than expected levels in the brain. By preventing reuptake into the neurons, SSRIs and SNRIs allow neurotransmitters to linger for a longer time in the brain, which helps to improve mental health symptoms.

SSRIs vs. SNRIs: What’s the Difference?

SSRIs and SNRIs are two common types of antidepressants. SSRI stands for “selective serotonin reuptake inhibitor,” while SNRI stands for “serotonin-norepinephrine reuptake inhibitor.”

SSRIs prevent the reuptake of serotonin into brain cells, causing it to stay in your brain longer. SNRIs work similarly on both serotonin and norepinephrine. By preventing the reuptake of certain neurotransmitters, SSRIs and SNRIs can help improve mental health symptoms.

Common SSRIs include:

• Sertraline (Zoloft)
• Fluvoxamine (Luvox)
• Fluoxetine (Prozac)
• Paroxetine (Paxil)
• Citalopram (Celexa)
• Escitalopram (Lexapro)

Common SNRIs include:

• Venlafaxine (Effexor)
• Desvenlafaxine (Pristiq)
• Duloxetine (Cymbalta)
• Milnacipran (Savella)
• Levomilnacipran (Fetzima)

How They Work

SSRIs only affect serotonin, working by preventing serotonin reuptake into brain cells. SNRIs are similar but work on both serotonin and norepinephrine. However, some SNRIs work more on one neurotransmitter than another. Specifically, milnacipran and levomilnacipran work more on norepinephrine as opposed to serotonin.

The concept behind how SSRIs and SNRIs work is similar for both drug classes. By leaving neurotransmitters in the brain for a longer period before reuptake occurs and they are broken down, brain chemistry is changed. The brain increases signaling of a chemical called cyclic AMP, activates and increases other brain chemicals and increases neural signaling. These effects help to treat symptoms of mental health conditions like depression or anxiety.

Uses

SSRIs and SNRIs are prescribed to treat many similar conditions, although this can vary on an individual drug level.

Side Effects

Overall, SSRIs and SNRIs share many side effects. These can include:

• Sleepiness
• Weight gain
• Sleep problems
• Anxiety
• Dizziness
• Headache
• Dry mouth
• Blurred vision
• Nausea
• Rash
• Tremor

Some side effects are more common with SSRIs than SNRIs and vice versa. For SSRIs, these include sexual dysfunction and heart rhythm problems. For SNRIs, these include high blood pressure, sweating and bone density problems.

Rare Side Effects

Rare side effects are similar for SSRIs and SNRIs. These can include:

• Weakness
• Malaise
• Lab abnormalities, such as low blood sodium levels or increased prolactin levels

One of the rarest side effects of antidepressant therapy is a condition called serotonin syndrome.

Risk for Serotonin Syndrome

Serotonin syndrome is rare, regardless of whether a person uses an SSRI or an SNRI. Typically, this condition occurs when a person takes multiple medications that increase serotonin levels. These can include:

• SSRIs or SNRIs
• Monoamine oxidase inhibitors
• Tricyclic antidepressants
• Migraine medications called triptans
• Meperidine
• Dextromethorphan

Serotonin syndrome is a medical emergency caused by an excess of serotonin in the brain. Its symptoms can include:

• Agitation 
• Restlessness 
• Abnormal eye movements 
• Diarrhea 
• Rapid heartbeat 
• High blood pressure or rapid changes in blood pressure
• Hallucinations 
• Fever
• Coordination problems
• Nausea or vomiting 
• Overactive reflexes 

If you suspect someone has serotonin syndrome, call 911 immediately for emergency medical assistance.

Interactions

SSRIs and SNRIs have similar drug interactions. Both classes of drugs are broken down by the liver enzyme CYP2D6, meaning that other drugs broken down by CYP2D6 may be impacted by SSRIs and SNRIs. These medications include:

• Some blood pressure medications, such as carvedilol and metoprolol
• Some antihistamines, such as chlorpheniramine
• The breast cancer medication tamoxifen
• Other psychiatric medications that use CYP2D6, such as other antidepressants

The exception to this is the SNRI milnacipran, which has few drug interactions because it is not broken down by CYP2D6, unlike other SSRIs and SNRIs.

Withdrawal

Both SSRIs and SNRIs can cause withdrawal if you suddenly stop taking them. Withdrawal doesn’t mean that you are addicted to the drug. Rather, it means that your body has become dependent on the medication over time and will struggle to adapt if you suddenly stop using it.

Withdrawal symptoms typically start within a few days after the last dose and last for a few weeks. Certain SSRIs and SNRIs may be more likely to cause withdrawal than others. For example, venlafaxine may be more likely to cause withdrawal than other SNRIs. Paroxetine and fluvoxamine may be more likely to cause withdrawal than other SSRIs.

SSRIs vs. SNRIs: Which One Is More Effective?

SSRIs and SNRIs are equally effective, and experts recommend both medications for the treatment of depression, anxiety disorders and obsessive-compulsive disorders.

Sometimes, the choice between the medications comes down to if the person has any other medical conditions. For example, SNRIs like duloxetine (Cymbalta) can be effective against nerve pain and fibromyalgia. Therefore, if a person has a mental health condition like depression as well as nerve pain, an SNRI may be a good option because it can treat both conditions.

Finding the Right Antidepressant for You

The most important thing to do when searching for the right antidepressant is to contact your doctor. Based on your medical history, mental health diagnosis and previous mood medications, your doctor will be able to recommend the best antidepressant for your needs. Sometimes, it can take switching medications a few times to find one that works well for your needs and has minimal side effects. In addition, some medications can take weeks to show their full effect, so patience is key.

In some cases, a person’s mood can worsen despite the use of antidepressants. If you start thinking about harming yourself or others, it is important to seek help immediately. The national suicide and crisis hotline number is 988, and a web-based chat exists as well. Other national and local depression hotlines are also available.

Keeping your mental health strong is vital to your quality of life. The free-to-use Nobu app can help supplement your treatment with a variety of mental health support services, including guided lessons, mindfulness exercises, journaling tools and more. For an additional fee, you can even connect with a licensed professional to receive professional mental health care and treatment. Find the support you’re looking for by downloading Nobu, available for free on both Apple and Android devices.