Serotonin-norepinephrine reuptake inhibitors (SNRIs) are a class of medication used to treat depression, anxiety, and other conditions. SNRIs work by affecting chemical messengers in the brain, which for some, may help regulate mood and relieve depression symptoms. SNRIs are sometimes prescribed for people who do not respond to selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed antidepressants.
What Are SNRIs?
Serotonin-norepinephrine reuptake inhibitors (SNRIs) are a family of medications commonly prescribed as FDA-approved treatments for depression and anxiety. However, SNRIs can also be used for chronic pain and other conditions as non-FDA-approved treatments (off-label uses). Although selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed first-line treatment, SNRIs are the second-most used medications for anxiety and depression.
Based on your health history, condition, and needs, your doctor might consider prescribing an SNRI.1 Regardless of the antidepressant used, the combination of medication and therapy is often recommended for the best symptom improvement.
Certain SNRIs are FDA-approved to treat the following conditions:2
- Depression
- Social anxiety disorder
- Panic disorders
- Dysthymia (persistent depressive disorder)
- Generalized anxiety disorder
- Chronic pain syndromes
- Fibromyalgia
- Chronic musculoskeletal pain
- Nerve damage from diabetes
- Osteoarthritis
SNRIs may be prescribed off-label (non-FDA approved) for the treatment of:
- Post-traumatic stress disorder (PTSD)
- Obsessive compulsive disorder (OCD)
- Premenstrual dysphoric disorder (PMDD)
- Migraine headaches
How Do SNRIs Work?
SNRIs affect the levels of two chemical messengers in the body, serotonin and norepinephrine.2 Increased amounts of these two chemicals may help the communication between brain cells, potentially improving mood and other symptoms of depression and anxiety.
SSRIs Vs SNRIs
SNRIs affect both serotonin and norepinephrine, whereas SSRIs only impact serotonin. For some, SSRIs may be more effective than SNRIs in the treatment of severe depression.3 It is possible that the increased norepinephrine action caused by SNRIs is what makes them effective in treating neuropathic pain.4 However, SNRIs might also directly block pain receptors. 5
A physician will choose an antidepressant, whether it be an SSRI or SNRI, or another class of medication, based on several factors. A person’s health history, other medications, age, and family health history all impact this decision. Both types of antidepressants are considered easy to use and generally safe because of their overall low occurrence of side effects.
Types of SNRI Drugs
Several different SNRI medications are available in the United States. While they each work to affect serotonin and norepinephrine levels, each drug has a unique chemical makeup. This means some medications stay in the body longer, whereas others may be more effective at treating specific conditions.
The most commonly prescribed SNRI medications include:
- Desvenlafaxine (Pristiq)*
- Duloxetine (Cymbalta)*
- Levomilnacipran (Fetzima)*
- Venlafaxine (Effexor XR)*
*SSRI box warning*
SNRI Side Effects
Some people experience side effects when taking SNRIs, with mild symptoms being the most common. Many of these effects may continue for as long as a person takes the medication. Side effects of SNRIs may impact digestion, blood pressure, heart rate, sexual function, and other functions. 6
Some people may get used to the side effects or find ways to cope with them, while others may find them intolerable. Side effects may cause people not to take their medications as intended and prescribed. Some side effects, even mild ones, may require medical care if they persist. Seek immediate care for more serious symptoms, such as seizures, ongoing vomiting, or excessive sedation.
Common side effects of SNRIs may include:
- Nervousness or anxiety
- Dry mouth
- Excessive energy levels
- Loss of appetite
- High blood pressure
- Increased suicidal ideation
- Nausea
- Vomiting
- Constipation
- Fatigue
- Sedation/Feeling drowsy
- Dizziness
- Sexual dysfunction
- Abnormal bleeding or bruising
- Seizures
Risks of Taking SNRIs
Antidepressants help many people with their symptoms, but they also come with some risks. The FDA has issued a warning about increased suicidal thoughts or behaviors with all antidepressants. Taking multiple medications with SNRIs increases the risk of harmful medication interactions. And while rare, taking medications that increase serotonin levels may lead to serotonin syndrome, a serious condition requiring immediate medical care.
Populations who may not be prescribed SNRIs include:
Children
The risks of treating children and adolescents with SNRIs need to be weighed against the benefits of symptom improvement. The FDA has issued a black box warning for all antidepressants, including SNRIs, about the increased risk of suicidal thoughts in adolescents and children. However, untreated depression and anxiety can also be harmful. Children taking SNRIs will need to see the prescribing doctor more often to monitor symptoms and side effects.
Pregnant & Breastfeeding Women
Pregnant and breastfeeding women understandably have concerns about taking medications, and SNRIs are no exception. However, the risks of leaving observed depression symptoms untreated may lead to more harm for the baby and the mother than other potential risks linked to the medication. Doctors can discuss how antidepressants can affect pregnancy and breastfeeding for women needing treatment. Together, they can consider these benefits and risks while monitoring for symptoms.
Those With Pre-Existing Health Conditions
People with pre-existing health conditions need to carefully consider the potential risks of taking an SNRI when discussing treatments with their doctor. SNRIs are known to affect liver function, blood pressure, heart rate, and other vital functions in the body. These medications may also trigger manic symptoms in people with bipolar disorder. Older adults are also more likely to have certain medical conditions and take multiple medications, creating additional risk.
Alcohol & SNRIs
Although it is generally not recommended to combine alcohol with antidepressants, including SNRIs, there is no adequate evidence that mild use of alcohol negatively interacts with SNRIs.6 However, this does not mean that it is a good idea to mix antidepressants and alcohol.
A person’s tolerance to alcohol tolerance may change when taking SNRIs or other antidepressants, which may increase the effects of intoxication, including the possibility of an episode of psychosis while intoxicated.4, 7 Further research is needed to understand this risk.
Antidepressant Discontinuation Syndrome
Antidepressant discontinuation syndrome can occur if a person abruptly stops taking an antidepressant, including SNRIs, a condition also known as antidepressant withdrawal. This condition may be prevented by tapering off the dosage under medical supervision. Symptoms of antidepressant discontinuation syndrome may include dizziness, headache, fatigue, agitation, and nausea.4 Seek immediate medical care if these symptoms arise.
Are SNRIs Right for Me?
If you are feeling depressed or anxious, there are many treatments available to help you manage your symptoms. The first step is seeking help from a professional, which may be a therapist, psychiatrist, or your primary care physician. Cognitive behavioral therapy (CBT) is a first-line treatment for depression and anxiety, but medications may be helpful for some.
CBT combined with medication has been proven to be the most effective treatment for depression and anxiety. If you are having trouble reaching your primary care physician or a psychiatrist in your local area, online psychiatry services may be a good option for you.
Questions to Ask Your Health Team About SNRIs
Starting treatment with an antidepressant, such as an SNRI, can be a life-changing decision. Speak with your doctor about your medical conditions, the medications you take, your family history, and any history of mental health issues. Make a plan with your therapist on how often you can schedule your sessions to augment the benefits of your medication. And if you don’t have a therapist, online therapy options may be a good fit for you.
Questions to ask your care team before taking SNRIs include:
- Will using an SNRI make my depression go away?
- How can I use SNRIs as part of my already-established anxiety treatment?
- How soon should I expect results?
- Are there SNRIs that might be helpful with treatment-resistant depression?
- Since this particular medication [insert name of medication] worked for my family member, can it be a better fit for me?
- Will using an SNRI make my depression go away?
- How often should I see you for checkups while taking SNRIs as part of my treatment?
- What are some online therapy options with my insurance that I can pair with my SNRI medication treatment?
- What are some concerning side effects that should make me call 911?
- What are some less concerning side effects that should make me call you?
- Why would SNRIs be a better fit for me compared to other antidepressants?
In My Experience
In my experience, SNRIs can be helpful in reducing symptoms of depression and anxiety. Talk with your doctor about whether SNRIs are right for you. Your therapist can address other ways to manage your symptoms while providing support along the way. Mental health issues can be challenging, but you do not have to cope with depression and anxiety alone.
For Further Reading
- Psychotherapy vs. Medication for Depression & Anxiety
- How to Get Antidepressants: Everything You Need to Know
- Pristiq & Alcohol: Everything You Need to Know
- Depression: Stopping Your Medications
- Pristiq Side Effects: Common, Severe, Long-Term, & What to Do About Them
- Non-SSRI Antidepressants: 10 Alternatives to Consider
