SNRI stands for serotonin-norepinephrine reuptake inhibitor. This class of medications is used in mental health care to help balance mood, energy, and anxiety by increasing the levels of two brain chemicals—serotonin and norepinephrine—in certain areas of the brain. SNRIs can be an effective option for many people, but they work differently for each person and come with potential side effects and monitoring needs. They are typically prescribed as part of a broader treatment plan that may include psychotherapy and lifestyle changes.
How SNRIs work
All SNRI medications block the reuptake of two neurotransmitters, serotonin and norepinephrine, meaning these chemicals remain available longer in the spaces between nerve cells. This modulation is thought to contribute to improvements in mood, motivation, and resilience to stress. The extent to which serotonin versus norepinephrine is affected varies by drug, which can influence both therapeutic effects and side effects. In addition to mood benefits, norepinephrine modulation can influence energy and alertness, and it can produce cardiovascular effects such as small changes in blood pressure or heart rate in some people. For this reason, clinicians monitor patients closely after starting or adjusting SNRI treatment, especially in the first weeks of therapy.
Common uses and conditions treated
SNRIs are approved for several psychiatric conditions and some chronic pain syndromes. They are often used when depression or anxiety disorders require a medication that also has a beneficial effect on physical symptoms like pain or fatigue. Examples of conditions treated with SNRIs include:
- Major depressive disorder (MDD)
- Generalized anxiety disorder (GAD)
- Social anxiety disorder
- Panic disorder
- Fibromyalgia (duloxetine and milnacipran have specific approvals)
- Peripheral neuropathic pain, diabetic neuropathy, and chronic musculoskeletal pain (duloxetine and venlafaxine are commonly used for these)
- Occasionally other anxiety or mood-related disorders on a case-by-case basis
Not every SNRI is approved for every condition, and some uses are off-label or guided by individual response. Your clinician will tailor the choice of SNRI and the dosing plan to your specific symptoms, medical history, and other treatments you may be receiving.
Typical dosages
Dosage recommendations vary by medication, formulation, and individual factors such as kidney or liver function. The following are general reference ranges and should not replace medical advice from your prescriber.
- Venlafaxine (Effexor, including extended-release): Start at about 37.5 mg once daily, then titrate. Typical maintenance ranges are 75–225 mg per day for the extended-release form; some cases use higher doses under close supervision. Immediate-release forms are usually divided into two or more doses per day.
- Duloxetine (Cymbalta): Start at 30 mg once daily for about a week, then 60 mg once daily. Common maintenance doses range from 60–120 mg daily; the 120 mg dose is often used for certain pain conditions or more resistant depression.
- Desvenlafaxine (Pristiq): Typically started at 50 mg once daily, with common maintenance ranging from 50–100 mg daily.
- Milnacipran (Savella): For fibromyalgia, start at low doses (e.g., 12.5 mg daily) and gradually increase to a typical target of 50–100 mg twice daily, depending on response and tolerability.
- Levomilnacipran (Fetzima): Start around 20 mg once daily, increasing in steps to reach 40–80 mg or more, with a common maximum around 120 mg daily in some patients.
Important notes:
- Always follow your clinician’s specific dosing instructions. Do not adjust dose or stop medication abruptly without medical guidance.
- Dose adjustments may be needed for kidney or liver disease, older adults, or when taken with other medicines that affect serotonin or norepinephrine.
Potential side effects and monitoring
Side effects from SNRIs are typically dose-related and often diminish after several weeks as the body adjusts. Common side effects include:
- Nausea, dry mouth, headache, dizziness
- Sweating, constipation, decreased appetite
- Nervousness or insomnia, fatigue, weight changes
- Sexual side effects such as reduced libido or difficulties with arousal
Some SNRIs can cause more serious concerns that require monitoring:
- Increases in blood pressure and heart rate (especially with venlafaxine and levomilnacipran in some people)
- Liver function changes, particularly with duloxetine, and especially in people with risk factors or prolonged use
- Hyponatremia (low blood sodium), more common in older adults or those with dehydration or diuretic use
- Serotonin syndrome risk when combined with other serotonergic medications (e.g., certain antidepressants, migraine medications like triptans, some pain medications)
- Withdrawal/discontinuation symptoms if the medication is stopped abruptly, including flu-like symptoms, dizziness, irritability, and sensory disturbances
Monitoring considerations include:
- Regular follow-up visits to assess mood, anxiety, sleep, and energy levels
- Blood pressure and heart rate checks after dose changes
- Liver and kidney function tests when long-term use or high doses are involved
- Screening for suicidal thoughts or unusual behavior, particularly early in treatment or after dose changes
Interactions with other medications
SNRI safety depends in part on other medicines you may be taking. Important interaction considerations include:
- Avoid concurrent use with monoamine oxidase inhibitors (MAOIs) or use only after an appropriate washout period, due to the risk of serious interactions such as serotonin syndrome.
- Be cautious with other serotonergic drugs (SSRIs, other SNRIs, certain pain medications like tramadol, some migraine therapies) because of the potential for serotonin syndrome.
- Nonsteroidal anti-inflammatory drugs (NSAIDs), anticoagulants, and antiplatelet agents can increase the risk of gastrointestinal bleeding or bruising; discuss bleeding risk with your clinician if you’re taking these regularly.
- Alcohol can worsen side effects such as dizziness or sleepiness and may interact with blood pressure effects.
- Some drugs can affect SNRI levels or vice versa, including certain antibiotics, antifungals, anticonvulsants, and HIV protease inhibitors. Always list all medications, supplements, and over-the-counter products you take with your prescriber.
Important considerations for patients
Several factors can influence the safe and effective use of SNRIs. Consider discussing these with your clinician:
trong> The safety of SNRIs during pregnancy varies by drug and week of gestation. Some SNRIs are associated with risks to the newborn or withdrawal symptoms after birth. A careful risk-benefit discussion with your obstetrician and psychiatrist is essential. trong> SNRIs can trigger mood swings, including mania, in people with bipolar spectrum illnesses. Mood stabilization strategies may be needed before starting SNRI therapy. trong> Some SNRIs require dose adjustments or are avoided in severe liver or kidney disease. Regular monitoring may be recommended for long-term use. trong> Hyponatremia and falls are considerations in older adults. Start with lower doses and monitor closely for dizziness, confusion, or mood changes. trong> Dizziness, drowsiness, or blurred vision can temporarily affect your ability to drive or operate machinery. Assess your reaction to the medication before engaging in risky activities. trong> If you need to discontinue, do so gradually under medical supervision to minimize withdrawal symptoms. Do not stop abruptly if you have been taking an SNRI for weeks or longer.
When to seek medical help
Contact a healthcare professional promptly if you notice any of the following:
- Severe or worsening mood symptoms, thoughts of self-harm or harming others
- Signs of a serious allergic reaction (rash, swelling of face or throat, trouble breathing)
- Severe headaches, chest pain, very high blood pressure readings, or fainting
- Seizures, confusion, fever, agitation, or abnormal muscle stiffness that could signal serotonin syndrome
- Persistent nausea, vomiting, or yellowing of the skin or eyes (possible liver concerns with duloxetine)
If you are considering SNRI therapy or have questions about ongoing treatment, discuss the risks, benefits, and monitoring plan with your clinician. They can help determine whether an SNRI is appropriate for you and tailor dosing, safety checks, and follow-up to your unique health needs.
