Duloxetine (Cymbalta): dosage, uses, side effects

Duloxetine (brand name Cymbalta) originally came to market in 2004 to treat depression. However, it quickly became the first drug FDA-approved to treat nerve pain, too. Since then, it has also been approved to treat other conditions, like anxiety and fibromyalgia. Read on to learn more about this versatile drug, including its uses, side effects, dosage, and more. 

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Cymbalta and generic duloxetine are serotonin-norepinephrine reuptake inhibitors or SNRIs, frequently used for depression and anxiety. Many healthcare providers also use Cymbalta for pain conditions, including diabetic nerve pain, fibromyalgia, etc.

Duloxetine works by affecting brain chemicals, called neurotransmitters, that help your nervous system communicate. The neurotransmitters are released in the spaces between the cells. Then, they are slowly reabsorbed back into the cells to use again in the future. Duloxetine works by blocking the reabsorption of two neurotransmitters—serotonin and norepinephrine—meaning the chemicals stay in the spaces between the nerves for longer and can continue communicating. Both of these neurotransmitters are important for mental health (Dhaliwal, 2020). 

Duloxetine is FDA approved to treat (FDA, 2019):

• Major depressive disorder (MDD or unipolar depression): MDD is a mental health condition where people experience a lack of desire to do anything, persistently sad moods, a sense of hopelessness or guilt, poor appetite, and other symptoms that disrupt day-to-day life (Bains, 2021).

• Generalized anxiety disorder (GAD): People with GAD feel excessive worry about many things, like home life, work stresses, personal relationships, etc., which can affect their ability to function. Taking Cymbalta for anxiety may help (Munir, 2021).

• Peripheral diabetic neuropathy: People with diabetes may experience numbness, tingling, and/or burning in their hands and feet (Bodman, 2021).

• Fibromyalgia: This is a widespread chronic pain condition related to problems processing pain in the brain (Bhargava, 2020).

• Chronic musculoskeletal pain: If you suffer from knee osteoarthritis or low back pain, your healthcare provider may recommend Cymbalta for the pain (UptoDate, n.d.). 

Sometimes healthcare providers use medications to treat conditions other than the FDA-approved ones. This is called using a drug “off label,” and such uses of duloxetine include (UptoDate, n.d.):

• Chemotherapy-induced peripheral neuropathy

• Stress urinary incontinence

If you've been prescribed Cymbalta for anxiety, pain, or another condition, you may be curious about potential side effects. Duloxetine is generally well-tolerated, but like many medications, it can cause adverse effects.

The U.S. Food and Drug Administration (FDA) has issued a black box warning for duloxetine and other antidepressants, noting worsening depression and an increased risk of suicidal thoughts and behavior in children, adolescents, and young adults (FDA, 2019).

Some of the common side effects of duloxetine include (Dhaliwal, 2020):

• Nausea

• Dry mouth

• Constipation

• Weight loss

• Decreased appetite

• Abdominal pain

• Drowsiness

• Headache

• Trouble sleeping

If you decide to stop taking duloxetine, talk to your healthcare provider first. Sudden discontinuation may lead to duloxetine withdrawal symptoms, including dizziness, nausea, and headache, among other symptoms (Hirsch, 2020).

Like many other antidepressants, sexual side effects can occur with Cymbalta, including abnormal orgasms, erectile dysfunction, decreased sex drive, and priapism (a painful and persistent erection) (UptoDate, n.d.). 

Serious side effects may occur, including suicidality, serotonin syndrome, liver problems, manic episodes (in people with undiagnosed bipolar disorder), bleeding, bone fractures, and SIADH (a condition that causes the body to retain too much water) (UptoDate, n.d.). 

Rarely, people experience severe skin reactions, including erythema multiforme and Stevens-Johnson Syndrome (SJS)—symptoms may include blisters, a peeling skin rash, or hypersensitivity. Another possible side effect is acute angle-closure glaucoma (a sudden spike in eye pressure), which can cause eye pain and lead to permanent vision loss if not treated immediately (UptoDate, n.d.). 

If you experience any serious effects or develop an allergic reaction to duloxetine, seek medical advice immediately. 

This list does not include all possible adverse effects, and others may exist. Check with your pharmacist or healthcare provider for more information.

Duloxetine is available in delayed-release capsules in doses of 20 mg, 30 mg, and 40 mg. Your healthcare provider may prescribe from 20 mg to 60 mg daily, split into one to three doses, depending on the condition being treated and other factors. 

Before starting duloxetine, tell your healthcare provider about any other medications or supplements you're taking to avoid potential drug interactions. Some medicines can increase the risk of adverse effects, while others may make duloxetine less effective.

Serotonin syndrome

The most serious potential drug interaction is serotonin syndrome, where serotonin levels become dangerously high in the body. Symptoms of serotonin syndrome include changes in mental status, increased heart rate, high blood pressure, loss of coordination, muscle rigidity or twitching, sweating, nausea, and vomiting. It can be fatal in severe circumstances (Simon, 2021). 

Duloxetine, as an SNRI, works by increasing the levels of serotonin and norepinephrine. However, too much serotonin can lead to serotonin syndrome, a serious potential side effect of duloxetine and other antidepressant drugs, like SSRIs (selective serotonin reuptake inhibitors). 

Some people have developed serotonin syndrome when taking duloxetine alone. However, the risk is higher if duloxetine is taken in combination with monoamine oxidase inhibitors (MAOIs), which may also be used to treat depression. Examples of MAOIs include SNRIs, SSRIs, or other medications and supplements that boost serotonin, including methylene blue, linezolid, and phenelzine. Do not take duloxetine five days before or 14 days after you have used an MAOI drug (FDA, 2019)

MAOIs are not the only drugs that may interact with Cymbalta to cause serotonin syndrome. Other medications that may increase serotonin levels include triptans, tricyclic antidepressants, lithium, tramadol, thioridazine, buspirone, amphetamines, and over-the-counter St. John's Wort (Simon, 2021).

Other drug interactions 

Another class of medications that can lead to potential drug interactions are CYP1A2 and CYP2D6 inhibitors. CYP1A2 and CYP2D6 are liver enzymes that break down duloxetine. Drugs that inhibit these enzymes may affect your duloxetine dose as these medications can increase the level of duloxetine in the blood. Examples include cimetidine, ciprofloxacin, paroxetine, fluoxetine, and quinidine (FDA, 2019).

Duloxetine may increase your risk of abnormal bleeding, like bruising, nose bleeds, and potentially life-threatening hemorrhages if taken with other medications that also affect bleeding, including aspirin, NSAIDs (nonsteroidal anti-inflammatory drugs) like ibuprofen or naproxen, and prescription blood thinners like warfarin (brand name Coumadin) (FDA, 2019):

Do not take duloxetine if you have had an allergic reaction to it in the past. 

Duloxetine should not be used by people with certain medical conditions like kidney disease or liver disease because of the increased risk of side effects (FDA, 2019).

People who drink heavily may experience severe liver injury if they take Cymbalta (FDA, 2019).

If you're pregnant, plan to become pregnant, or breastfeeding, talk with your healthcare provider before taking duloxetine. Duloxetine is an FDA pregnancy Category C drug, which means that risks to the fetus can't be ruled out (FDA, 2019). Your healthcare provider will work with you to determine if it’s safe to keep you on Cymbalta during pregnancy. 

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Every article on Health Guide goes through rigorous fact-checking by our team of medical reviewers. Our reviewers are trained medical professionals who ensure each article contains the most up-to-date information, and that medical details have been correctly interpreted by the writer.

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Current version

June 25, 2021

Written by

Michael Martin

Fact checked by

Chimene Richa, MD

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About the medical reviewer

Chimene Richa, MD

Dr. Richa is a board-certified Ophthalmologist and medical writer for Ro.