Cymbalta for Musculoskeletal Pain

Cymbalta (duloxetine hydrochloride) is a selective serotonin and norepinephrine reuptake inhibitor (SNRI). It is a prescription-only drug approved for the treatment of chronic musculoskeletal pain and chronic low back pain, which can be caused by conditions such as osteoarthritis.

Cymbalta was first approved by the Food and Drug Administration (FDA) in 2004 for major depressive disorder. Subsequently, it was also approved for the treatment of anxiety, pain caused by diabetic neuropathy, and pain caused by fibromyalgia before gaining FDA approval for chronic musculoskeletal pain in 2010.

Woman with wrist pain
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How It Works

Cymbalta increases the action of serotonin and norepinephrine, which are natural neurotransmitters produced by the body. This effect of Cymbalta alleviates depression and anxiety and decreases pain signals in the brain, spinal cord, and nerves.

Prior to the approval of Cymbalta for musculoskeletal pain, several double-blind, placebo-controlled, randomized clinical trials confirmed that study participants taking Cymbalta experienced significantly greater pain reduction than participants taking a placebo.

Cymbalta does not treat the underlying damage in osteoarthritis or any of the other causes of chronic musculoskeletal pain. It only reduces the pain sensation, so you may need to take another medication to treat the illness itself.

Since its approval, more recent studies have shown that Cymbalta reduces chronic musculoskeletal pain, including that from osteoarthritis. However, it does have three to four times more reported gastrointestinal side effects than placebo.

Side Effects

Like any medication, Cymbalta has potential side effects and other considerations that you must weigh before deciding to take it.

Common side effects include:

  • Nausea
  • Dry mouth
  • Constipation
  • Sleepiness
  • Sweating
  • Decreased appetite

Though less common, Cymbalta may also cause:

  • Vomiting
  • Diarrhea
  • Stomach pain
  • Urinary retention
  • Dizziness
  • Headaches
  • Tiredness
  • Muscle pain
  • Muscle cramps
  • Diminished sexual functioning
  • Shaking

Serious side effects are not common, but they can have major consequences. The most serious side effects associated with Cymbalta include:

  • Bleeding: This is more likely if you have a bleeding disorder or if you are taking a blood thinner.
  • Liver toxicity: Cymbalta might cause liver failure and should not be prescribed to people with chronic liver disease or substantial alcohol use.
  • Severe skin reactions: Cymbalta might result in the appearance of blisters, rash, and other signs of hypersensitive skin.
  • Seizures: Cymbalta may lower the seizure threshold, causing increased seizures in people with epilepsy.
  • Mania: Because of its antidepressant effect, Cymbalta may cause a hyperactive and unfocused state of mind.
  • Low blood pressure: A warning was added to Cymbalta in 2014 for orthostatic hypotension, falls, and syncope (fainting).
  • Serotonin syndrome: Especially when combined with other medications that increase serotonin, Cymbalta may cause a life-threatening condition that includes anxiety, high blood pressure, rapid heartbeat, rapid breathing, sweating, and tremors
  • Suicidal thoughts and behaviors: Cymbalta had a black box warning related to this concern added in 2014.

Black Box Warning

According to prescribing information for Cymbalta provided by the manufacturer, Cymbalta causes an increased risk of suicidal thinking and behavior in children, adolescents, and young adults. It is recommended that you, your family, and your caregivers monitor for agitation, irritability, unusual changes in behavior, and suicidality. Report any of these immediately to your healthcare provider.


Taking Cymbalta either along with or within 14 days of stopping monoamine oxidase inhibitors (a type of antidepressant) is contraindicated.

Possible Interactions

Certain medications may increase or decrease the effect of Cymbalta, or cause different side effects. Several categories of medications have been proven to interact with Cymbalta, including the following:

  • Alcohol, which, in combination with Cymbalta, can cause severe liver injury
  • Quinolones, such as ciprofloxacin and fluoroquinolone
  • Antidepressants, including nortriptyline, amitriptyline, and imipramine
  • Antipsychotic medications, especially thioridazine
  • Antiarrhythmics, including propafenone and flecainide
  • Narcotic pain medications, such as codeine and oxycodone
  • Blood thinners, such as warfarin, heparin, rivaroxaban, and aspirin
  • All sleep medications and tranquilizers, because they are known to have an additive effect resulting in excessive drowsiness

Taking Cymbalta

Cymbalta comes as a delayed-release capsule in 20-, 30-, and 60-milligram (mg) strengths. It is usually recommended that you start with an initial dose of 30 mg per day and increase to the target dose of 60 mg daily within a week. Take your prescription according to directions on the label.

Be sure to swallow the capsule whole without crushing, splitting, chewing, or opening it. You can take Cymbalta with or without food, but eating something can help prevent stomach upset.

Do not stop taking Cymbalta abruptly or without first discussing discontinuation with your healthcare provider. Doing so may cause you to experience withdrawal effects including dizziness, nausea, vomiting, headaches, tingling, fatigue, irritability, anxiety, insomnia, diarrhea, or hyperhidrosis (too much sweating).

A Word From Verywell

While Cymbalta is an approved treatment for chronic musculoskeletal pain, not everyone tolerates the medication or experiences the same degree of pain relief from it; some do not experience pain relief at all. Remember that your experience may differ from someone else's, both in terms of how well the medication works for you and what side effects you experience. Monitor your pain and alert your healthcare provider to any concerns promptly.

4 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. National Center for Biotechnology Information. PubChem Database. Duloxetine hydrochloride, CID=60834.

  2. U.S. National Library of Medicine DailyMed. Label: Duloxetine—duloxetine hydrochloride capsule, delayed release.

  3. Osani MC, Bannuru RR. Efficacy and safety of duloxetine in osteoarthritis: a systematic review and meta-analysis. Korean J Intern Med. 2019;34(5):966–973. doi:10.3904/kjim.2018.460

  4. U.S. National Library of Medicine MedlinePlus. Duloxetine.

Additional Reading

By Carol Eustice
Carol Eustice is a writer who covers arthritis and chronic illness. She is the author of "The Everything Health Guide to Arthritis."