Written by Hafsa Saleemi,
Medically reviewed by:
Mimi Winsberg, MD
Chief Medical Officer
Perhaps you have heard of SNRIs and SSRIs, but which is best for depression?
When it comes to treating depression, psychiatric providers have several medication options to choose from. The most popular medications, and generally considered the first option for most people with moderate to severe symptoms, are selective serotonin reuptake inhibitors (SSRI). But if these aren’t effective for the individual, or if SSRIs aren’t the best choice for other reasons such as side effects, doctors will examine alternatives to SSRIs to treat depression. One of the SSRI alternatives they may explore for depression is a class of medicines called serotonin and norepinephrine reuptake inhibitors, also known as SNRIs.
It can be difficult to determine whether SNRIs or SSRIs will be best for depression within an individual, so let’s take a look at how each class of medication works, and what may cause a provider to encourage one over the other.
How does an SSRI work?
As we said above, selective serotonin reuptake inhibitors (SSRIs) are often the first choice in treating depression. The Mayo Clinic says that SSRIs “are the most commonly prescribed antidepressants. They can ease symptoms of moderate to severe depression, are relatively safe, and typically cause fewer side effects than other types of antidepressants do.”
Our psychiatric providers use SSRIs to help balance the serotonin levels in your brain—increasing those levels can improve your mood. Serotonin is one of the major chemical messengers (neurotransmitters) used to carry a signal from one brain cell to another.
SSRIs make more serotonin available in the brain. This may help your brain grow new cells and form stronger connections between neurons. SSRIs do this by blocking the reuptake of serotonin, which means more serotonin is available to help transmit messages between neurons.
SSRIs may also help generate cells in an important part of your brain that regulates mood and anxiety. This region is called the dorsolateral prefrontal cortex (DLPFC). When cells in this region are activated, they can help regulate mood, memories, anxiety, anger, and fear.
There are several SSRI options on the market, including name brands like Prozac (fluoxetine), Zoloft (sertraline), Celexa (citalopram), and Lexapro (escitalopram). Your psychiatric provider will determine which of these SSRIs are best for depression and at what dose, as efficacy depends on several factors and interactions.
How does an SNRI work?
Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a newer class of medicines that work just a bit differently than SSRIs. It’s this difference that may help a provider determine whether an SSRI or an SNRI will better treat your unique depression symptoms.
The key distinction lies in the inhibition of the reabsorption of norepinephrine. As implied in their name, SNRIs prevent the brain from reabsorbing both serotonin (like SSRIs) and the neurotransmitter norepinephrine. As a result, SNRIs can boost levels of serotonin and norepinephrine—neurotransmitters, or chemical messengers, in your brain that affect your mood.
Serotonin creates feelings of well-being, and norepinephrine promotes alertness and energy. SNRIs work by increasing available amounts of these neurotransmitters in the brain, making you feel better and improving symptoms of depression and anxiety.
Some of the most common brand names for SNRIs include Cymbalta (duloxetine) and Effexor (venlafaxine).
SNRI vs SSRI for depression: How do you choose the right one for you?
If SNRIs work on norepinephrine as well as serotonin, then doesn’t that make them a better alternative than SSRIs for depression? Not necessarily.
Both SSRIs and SNRIs have side effects that impact each individual differently. SNRIs are typically second-line agents when an SSRI has failed because in general SSRIs have fewer side effects, but sometimes SNRIs are used to treat specific conditions such as chronic pain. The Mayo Clinic says:
All SNRIs work in a similar way and generally can cause similar side effects, though some people may not experience any side effects. Side effects are usually mild and go away after the first few weeks of treatment.
Some of the common side effects for SNRIs, The Mayo Clinic continues, include headaches, nausea, dizziness, and changes in sexual function, such as reduced sexual desire, difficulty reaching orgasm or the inability to maintain an erection (erectile dysfunction). It’s worth noting that the side effects list is very similar to the one they list for SSRIs.
In deciding whether to prescribe SSRIs or SNRIs for depression, a provider will take all of these side effects into account, and will also evaluate any interactions the medicines may have with anything you are currently taking. All of these factors will also help your provider determine which particular SNRI or SSRI is best for your depression. As we explain on our blog, “If you try one SSRI and find that your body does not tolerate it well, you may still be able to tolerate a different SSRI. If you are experiencing unwanted side effects, your provider will work with you to adjust your medication or recommend another SSRI that may be a better fit for your needs.” And if they can’t meet that need with an SSRI, then they may try an SNRI.
Generally speaking, a provider will work to find a medication for which the benefits far outweigh any side effects. Typically, that may take a bit of trial and error—however, at Brightside, our providers have access to our clinical decision-making tool, PrecisionRx, which supports them in personalizing treatment to you and finding the right SSRI, SNRI, or other medication to get on top of depression.
Are SNRIs or SSRIs better for depression?
The truth is, it’s impossible to know for sure or even to tell which SNRI or SSRI is best for depression, without knowing a lot of specifics about an individual, their specific depression symptoms or presentation, their comorbidities, and more. On our blog we explain, “Experiences with depression may vary as individuals respond to medications in different ways. This is why matching you with the right medication for your individual needs is essential.”
What we can tell you is that, if you are experiencing depression, you and your Brightside provider can find the best SSRI or SNRI for you, if medication is the right choice. Your provider will want to know about your needs and family medical history, and they may try more than one medication before they find the right fit. Using our precision psychiatry technology, Brightside analyzes a variety of data about a member, including preferences and present symptoms, to recommend the medication that is likely to be most tolerable and effective for you. In a representative study of over 6K Brightside members, conventional prescribing practices only covered 13% of the unique treatment plans we prescribed.
Your provider may also recommend alternatives to SSRIs to treat your depression —an MAOI for example, or treatment that includes therapy. Treating depression often takes a combination of medication and therapy.