10 Things to Know Before Starting an SNRI Like Cymbalta

There are many types of medications that affect the brain in order to help treat various health conditions. Antidepressants are one such example. Serotonin and norepinephrine reuptake inhibitors (SNRIs) are one class of antidepressants, and they’re among the most effective antidepressants available.

But they can treat more than just depression. Many SNRIs are also prescribed for anxiety, nerve pain due to diabetes, and certain types of chronic pain.

And although they can be effective, there are a few things to know about when taking an SNRI. This includes things like side effects and interactions. Here, we’ll answer 10 common questions you might have before starting an SNRI.

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1. What are SNRIs?

As mentioned above, SNRIs are a type of antidepressant. The first SNRI became available in the U.S. in 1993, and the most recent one was FDA approved in 2013. SNRIs share many similarities, but there are a few differences between them.

A few examples of SNRIs include:

• Cymbalta (duloxetine)

• Effexor XR (venlafaxine)

• Pristiq (desvenlafaxine)

• Savella (milnacipran)

• Fetzima (levomilnacipran)

All SNRIs are oral medications, taken one or more times daily. They’re available by prescription only. Some of them are brand-name only, and others have lower-cost generic versions.

2. How do SNRIs work?

SNRIs work by raising levels of the chemicals serotonin and norepinephrine in the brain and spinal cord. Serotonin and norepinephrine are thought to regulate body functions such as mood, attention, and stress. That’s why these medications are often used for mental health conditions.

Norepinephrine also plays a role in how the brain perceives pain. Higher levels of norepinephrine in the spinal cord seem to decrease the amount of pain experienced through the body. That’s why SNRIs can be helpful in treating certain types of chronic pain.

Certain SNRIs affect serotonin more than norepinephrine and vice versa. For example, Savella and Fetzima are thought to work more on norepinephrine than serotonin.

3. What are the common side effects of SNRIs?

Common side effects of SNRIs vary with each medication. But generally, the most common side effects are stomach-related.

Possible SNRI side effects include:

• Nausea

• Vomiting

• Diarrhea or constipation

• Dry mouth

• Lower appetite than normal

• Headache

• Dizziness

• Drowsiness

• Trouble sleeping

• Weight gain

• Sexual side effects, such as erectile dysfunction

• Excessive sweating

• Emotional blunting (feel numb to positive and negative emotions)

More serious side effects of SNRIs are also possible, but they’re more rare:

• Suicidal thoughts or behaviors, primarily in the first few months of treatment

• Higher blood pressure

• Serotonin syndrome

• Low sodium levels

If you or someone you know is having thoughts of suicide, you’re not alone, and help is available. Call the National Suicide Prevention Lifeline at 988, or text HOME to 741-741 to reach the Crisis Text Line.

4. How do SNRIs make you feel?

SNRIs typically help improve mood and increase cognitive function (like focus and memory). They can also help relieve physical symptoms of depression, such as headaches or pain. When taken for chronic pain, they can help lower the amount of pain you feel over time.

Ideally, as an SNRI starts to work for depression or anxiety, you’ll feel fewer symptoms. You may also notice positive changes in related emotions, such as happiness and a sense of calmness. People who take SNRIs may also feel more engaged and motivated.

Along with behavioral therapy and counseling for mental health conditions, SNRIs can be an effective way to help bring balance back into your life — mentally and physically.

5. How quickly do SNRIs work?

For mental health conditions, SNRIs are expected to work within 1 to 2 months. Some people notice improvements in symptoms within the first 2 weeks of taking an SNRI. And many people report significant improvement within 2 to 4 weeks after starting.

For pain relief, such as with diabetic nerve pain and fibromyalgia, SNRIs might take up to 12 weeks (3 months) for noticeable benefit. But some people may start to have pain relief sooner.

6. What medications do SNRIs interact with?

SNRIs like Cymbalta may not be safe to combine with certain medications or substances. Specific interactions vary between SNRIs. So be sure to share a medication list with your healthcare provider and pharmacist so they can screen for potential interactions.

Some SNRI interactions include:

• Medications that raise serotonin levels, like other antidepressants and St. John’s wort

• Nonsteroidal anti-inflammatory drugs (NSAIDs), like ibuprofen (Advil, Motrin)

• Medications that may cause bleeding, like warfarin (Coumadin, Jantoven)

• Alcohol

7. What is the difference between SNRIs and SSRIs?

Selective serotonin reuptake inhibitors (SSRIs) are another popular group of antidepressants. SNRIs and SSRIs are very similar medications. Both raise serotonin levels in the brain. Both can help treat conditions like anxiety and depression. And, they have similar side effects and risks for interactions.

But there are a few key differences:

• SNRIs also affect norepinephrine in the brain, whereas SSRIs do not.

• SNRIs can help treat certain types of chronic pain, while SSRIs don’t seem to have much benefit.

• SNRIs can cause higher blood pressure, whereas this is not a typical side effect of SSRIs.

Overall, SNRIs and SSRIs are similar but not interchangeable.

8. What happens when you stop taking an SNRI?

When you stop taking an SNRI, you might experience withdrawal symptoms, also called discontinuation syndrome. This is thought to be caused by a sudden drop in chemicals in the brain, such as serotonin and norepinephrine. These symptoms are more likely to happen if you stop taking them, or reduce your dose, too quickly.

Symptoms of discontinuation syndrome include:

• Headache

• Dizziness

• Upset stomach

• Nausea and vomiting

• Feeling tired

• Muscle aches

• Balance problems

• Trouble sleeping

• Sensations of “pins and needles” or “electric shocks”

• Irritability, agitation, or restlessness

• Feeling anxious

Withdrawal symptoms are temporary, usually lasting 1 to 2 weeks. But the symptoms can be unpleasant, and they are often avoidable.

If you feel that you need to stop taking your SNRI, talk to your healthcare provider first. They can recommend a schedule to lower your dosage gradually. This can help limit or prevent withdrawal symptoms.

9. Can SNRIs make you feel worse?

For the most part, your health condition symptoms shouldn’t get worse while taking an SNRI. But there are times these medications may make people feel uncomfortable or question whether an SNRI is “worth it.”

Here’s are some situations in which an SNRIs might make you feel worse:

• When you first start taking one or have a dose increase (side effects tend to be more common then)

• Stopping an SNRI abruptly (may cause discontinuation syndrome, as discussed above)

• If you have bothersome or excessive side effects

• If an SNRI interacts with another medication you’re taking

• If you’re allergic to the medication and experience symptoms like hives or trouble breathing

If you’re feeling worse after starting an SNRI, talk to your healthcare provider. They can help you know how to manage your symptoms. They can also advise whether your symptoms might be temporary and will likely resolve. Or, they may suggest stopping the medication if you’re having more serious problems.

10. When should I talk to my healthcare provider about taking SNRIs?

If you’ve just been prescribed an SNRI, you should talk to your healthcare provider about what to expect. They can review your specific dosage and why you’re taking the medication. This will help you to know what to look for when starting the medication.

If you’re not taking an SNRI yet, but wondering if you should, it’s also worth checking with your healthcare provider. While many people take SNRIs, taking one of these medications may or may not be the best option for you. You and your healthcare provider can decide together the best treatment for your condition.

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Written by:

Austin Ulrich, PharmD, BCACP

Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. In his early career, he provided direct patient care in a variety of settings, including hospital and community pharmacies, and in a primary care clinic as a clinical pharmacist.

Edited by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

Reviewed by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

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