What Is The Difference Between An SSRI And An SNRI?

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Note: The information found in this article is not a substitute for professional medical advice. Seek the advice of your physician or other qualified health providers with any questions you may have. In addition, consult a medical doctor before starting, changing, or stopping any medication or medical treatment. 

Understanding your medications and their intended use may help you and your healthcare provider determine their effectiveness. Various mental health conditions and physical illnesses can be treated with medications. However, side effects and efficacy can differ for everyone. If you have been diagnosed with a mental health condition and your healthcare provider advises that you take antidepressant medication to manage symptoms, it can be valuable to be well-informed about the medicine. 

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Overview: Neurotransmitters and depressive disorders

While the exact cause of depressive disorders is unknown, studies have suggested that disturbances in serotonin, dopamine, and norepinephrine messaging in the central nervous system may lead to the development of a depressive disorder. Both serotonin and dopamine are neurotransmitters, chemical messengers that control core functions in the human body, including mood and emotions. Below are a few ways these chemicals and neurotransmitters interact with the brain and body. 

Dopamine 

Dopamine is integral to the brain's reward system and influences learning, movement, mood, and sleep. It is also a precursor to the release of norepinephrine and epinephrine. 

Serotonin

Serotonin is a neurotransmitter, a chemical that transmits messages between nerve cells in the brain. It can also be found in the other parts of the central nervous system, smooth muscles of the cardiovascular and bronchial systems, and small amounts in the digestive system. 

Serotonin plays a significant role in controlling emotions, mood, and it is implicated in aggression, depressive conditions, and anxiety disorders. If your serotonin levels are low or high, you may experience physical and psychological symptoms. For example, serotonin is derived from tryptophan, an amino acid present in foods. If your diet is low in tryptophan, it may lead to serotonin deficiency, which can cause a depressed mood or anxiety. 

Norepinephrine 

Like serotonin and dopamine, norepinephrine is a neurotransmitter that transmits nerve messages to elicit a response in the body. The interplay between these three neurotransmitters improves mood, builds resilience against stress, and increases energy. As dopamine and serotonin work to control emotions and improve cognitive functions, epinephrine – a hormone released during the fight-or-flight response – causes a boost of energy along with clarity of thought and attentiveness. 

What are SSRIs and SNRIs? 

When considering neurotransmitters' roles in managing energy, concentration, mood, and overall cognition, one may begin to understand why they are a target when looking for a way to manage symptoms of depressive disorders. There are two main types of antidepressants that target serotonin and norepinephrine receptors, known as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Although both classes are labeled as antidepressants, they can each be used to treat numerous mental health conditions, like depression, anxiety, post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD). 

SSRIs: Selective serotonin reuptake inhibitors 

Serotonin levels can be boosted in several ways, including increasing the amount of serotonin available or decreasing the amount of serotonin lost through reuptake. The most common choice to improve serotonin levels is using an antidepressant called an SSRI. An SSRI works by increasing the level of serotonin available in the bloodstream by blocking the receptors that reabsorb it. 

SSRIs can cause serotonin levels to rise to dangerous levels in the body, leading to a condition known as serotonin syndrome. While it may seem that excessive serotonin may put you in a better mood, serotonin syndrome can potentially be life-threatening. Serotonin syndrome can be caused by the therapeutic use of serotonergic substances, like SSRIs and other serotonergic medications, related to an overdose, or result from an interaction between multiple similar medications. 

If your serotonin levels get too high, you may notice symptoms like the following: 

  • Shivering
  • Diarrhea
  • Confusion
  • Headaches
  • Twitches
  • Heart palpitations
  • Seizures
  • High blood pressure
  • Muscle spasms

A blood test may not detect serotonin syndrome. If you experience any of the above symptoms and have recently started taking an SSRI or had your SSRI dosage increased, speak with your doctor immediately. If left untreated, serotonin syndrome can be fatal.

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SNRIs: Serotonin and norepinephrine reuptake inhibitors

Serotonin and norepinephrine reuptake inhibitors (SNRIs) work slightly differently than SSRIs. Though both medications increase the amount of serotonin available in the bloodstream, SNRIs block the reabsorption of serotonin and norepinephrine. While SSRIs are mainly used only for mental health conditions, SNRIs can also be used for other conditions (like to relieve pain), and they are more effective for certain people. SNRIs may be less likely to cause rapid mood cycling in people with bipolar disorder. They are more often prescribed only for short-term use for depression in those with bipolar disorder due to the risk of hypomania or mania after use. 

These medications are not only used to treat depression, anxiety, and other mental health disorders, but they also are effective in treating fibromyalgia and nerve pain due to their effect on norepinephrine levels, which has a natural analgesic (pain killing) effect. SNRIs were created in the 1990s and are newer than SSRIs, which are from the 1980s. Providers usually recommend that SNRIs are not taken with SSRIs because of the risk of serotonin syndrome. 

Like SSRIs, SNRIs can cause serotonin syndrome by raising serotonin levels to dangerously high levels. Other symptoms, like anxiety, sweating, and restlessness, are more likely with SNRIs for select people. In addition, SNRIs may cause liver problems if used long-term. With both SSRIs and SNRIs, there are risks of suicidal thoughts and behaviors, especially in children and adolescents. 

If you are experiencing suicidal thoughts or urges, call the 988 Suicide & Crisis Lifeline at 988 or text 988 to talk to a crisis provider over SMS. They are available 24/7 to offer support. 988 also offers an online chat for those with an internet connection.

Both types of medications have serious withdrawal symptoms. Consult your doctor before making any changes. Withdrawal signs can include anxiety, upset stomach and diarrhea, tiredness, and muscle aches. Alcohol can worsen withdrawal symptoms and increase the risk of serotonin syndrome. Neither can be prescribed to pregnant and nursing women.

SSRIs and SNRIs: Is one better than the other? 

Serotonin is responsible for various bodily functions, including emotional control, sleep cycling, and cognitive functions. When treating depression, physicians may consider using an SSRI or SNRI. While these medications are most often prescribed for depression, they have other uses too. 

SSRIs target serotonin levels alone, so are usually used only to treat depression and anxiety. An upset stomach is a common symptom of anxiety and depression and may be related to low serotonin levels. This relationship is known as the "brain-gut connection," as the neurological system that lines the gastrointestinal tract is also known to utilize serotonin. For this reason, SSRIs may also be used to treat gastrointestinal stress. 


SNRIs inhibit the absorption of norepinephrine, a neurotransmitter known to inhibit pain when levels are increased. Norepinephrine is released during a fight-or-flight response and stimulates the adrenal system. The stimulus of this hormone can raise the heart rate and blood pressure, increase energy, cause the blood to thin, and increase attentiveness.

These medication effects make SNRIs an option for treating not only depressive disorders but also pain disorders like fibromyalgia and low blood pressure. Evidence also shows SNRIs may reduce symptoms of migraines and other pain-related symptoms. Still, SNRIs are more rarely used for these conditions due to better or more effective medications available. 

Are SNRIs or SSRIs more effective? 

According to research, certain SNRIs showed better results compared to all other SSRI medications given to clients with severe depression. SNRIs may be more expensive than SSRIs. However, the cost can vary, based on insurance, location, and year.   

Some doctors combine antidepressants for treatment-resistant depression. One potential challenge with SSRIs and SNRI medications is that, while they are often considered to be highly effective, their effectiveness can decrease over time. For this reason, doctors may have clients switch medications after prolonged use of a single antidepressant. Talk to your doctor if you notice worsening symptoms. 

SNRIs’ additional effect on norepinephrine levels means that SNRIs improve energy levels in addition to one's overall mood. While SNRIs may appear to be a more effective choice overall, each person is unique, and what works for one may not work for another. Some people may find significant improvement with SSRIs. Your doctor can work with you to find a medication that meets your unique needs. 

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Other support options

Because medications are often offered temporarily, therapy can be used alongside treatment for more long-term care. A therapist can help you develop coping mechanisms unique to your condition and talk about how your symptoms impact your life. They may also offer worksheets, external resources, and activities to practice. 

If you are facing any challenges that keep you from seeking therapeutic support in your area, you might also consider online counseling through a platform like BetterHelp, which may be more convenient. Online platforms allow you to be matched with a practitioner based on your preferences. Although they do not offer medication management or prescription, you can learn various therapeutic modalities and techniques with your therapist from home. In addition, you can pick between phone, video, or chat sessions. 

One study found that online therapy's Working Alliance Index score was higher than in-person therapy in several areas. The composite score for online therapy was 215.07, compared to 205.5 for face-to-face therapy. Study participants primarily sought therapy for depression, anxiety, and relationship challenges. They cited written communication, cost, and flexibility as factors contributing to their overall positive experience with online therapy compared to in-person options. 

Takeaway

Acronyms like SSRI and SNRI may be difficult to distinguish at first. Understanding their definitions may aid you in being informed as you receive treatment. With this information, you can discuss which option is right for you with your doctor. Both can be effective tools. Alongside medication or as an alternative, consider working with a therapist for compassionate support and guidance.
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