Duloxetine for Multiple Sclerosis

Last updated July 20, 2022, by Marisa Wexler, MS

Fact-checked by Inês Martins, PhD

What is duloxetine for MS?

Duloxetine is an oral therapy approved by the U.S. Food and Drug Administration (FDA) for the treatment of depression, anxiety, and a number of pain disorders.

In people with multiple sclerosis (MS), it is sometimes prescribed to help manage depression, and it also is used off-label for pain resulting from nerve damage, called neuropathic pain.

In the U.S., duloxetine is sold under the brand names Cymbalta and Drizalma Sprinkle. Generic versions of the medication also are available.

How does duloxetine work?

The neurotransmitter serotonin is a chemical messenger that nerve cells use to communicate with each other and the rest of the body. It is believed to have a positive impact on mood, emotion, and sleep. It also has a potent analgesic effect that helps to ease pain.

Typically, nerve cells release serotonin into the space near other cells, allowing a signal to be sent between them. Specialized proteins on the original nerve then re-absorb the neurotransmitter for later use.

Duloxetine belongs to a class of antidepressants called selective serotonin reuptake inhibitors, or SSRIs, which work by blocking the reuptake of serotonin. This ultimately increases the amount of the neurotransmitter that is outside the nerve cell, boosting the power of the signal.

Increasing the potency of these neurological signals is thought to be the main mechanism by which duloxetine exerts its therapeutic effects — for example, helping to normalize irregular brain activity that gives rise to depressive symptoms or neuropathic pain.

Who should not use duloxetine?

Duloxetine should not be used in combination with monoamine oxidase inhibitors (MAOIs), another class of antidepressants that works by preventing the breakdown of serotonin and other neurotransmitters. People who have taken an MAOI should wait at least two weeks after their last MAOI dose before taking duloxetine.

The therapy also should not be given to people treated with the antibiotic linezolid or intravenous methylene blue, which also can inhibit the monoamine oxidase enzyme and contribute to serotonin toxicity.

Individuals with severe kidney impairment, chronic liver disease, or liver scarring (cirrhosis) should avoid taking duloxetine.

How is duloxetine administered in MS?

Duloxetine is available as delayed-release oral capsules that come in three strengths: [here]

  • 20 mg green capsules
  • 30 mg white and blue capsules
  • 60 mg green and blue capsules

The capsules can be taken with or without food. They should be swallowed whole, and not chewed, crushed, or sprinkled on food or into liquids.

The recommended daily dosage of duloxetine varies depending on the condition being treated, and doses are usually adjusted based on how the person responds to treatment. For depression, the recommended starting dose is 40 to 60 mg/day, followed by maintenance treatment at 60 mg/day, with a maximum recommended dose of 120 mg/day. Similar dose ranges have been used in clinical studies of duloxetine for neuropathic pain in MS.

Duloxetine in MS clinical trials

Eli Lilly, which markets Cymbalta, sponsored a Phase 3 clinical trial (NCT00755807) that enrolled 239 adults with MS-related neuropathic pain. The participants were primarily female (74.9%), white (92.5%), and had relapsing-remitting disease (64%). Most could walk.

Pain was self-reported on a scale from 0 to 10, with higher numbers reflecting worse pain — all participants had a pain score of 4 or higher at the study’s start.

For the first six weeks, participants were randomly assigned to take duloxetine (30 mg/day for one week, then 60 mg/day thereafter) or a placebo.

Results showed that average pain scores decreased significantly more in patients given duloxetine compared with those on a placebo (1.83 vs. 1.07). The difference between groups was evident as soon as one week after starting treatment.

Notably, however, more participants given duloxetine than placebo (13.6% vs. 4.1%) withdrew from the study in the first six weeks due to side effects, mainly dizziness or drowsiness.

A total of 209 participants then entered the open-label part of the trial, in which all were given treatment with duloxetine for 12 weeks. Patients started with a 30 mg daily dose in the first week, increased to 60 mg in the following week, and could then go up to 120 mg/day with 30 mg/day increments at the physician’s discretion.

Results broadly showed that pain scores kept decreasing for patients continuing on duloxetine, but those who had originally been given a placebo reported even more marked reductions in pain scores after starting on duloxetine in the open-label portion.

Common side effects of duloxetine

In adults, the most common side effects of duloxetine include:

  • nausea
  • dry mouth
  • sleepiness, known as somnolence
  • constipation
  • decreased appetite
  • excessive sweating

In children treated with duloxetine, common side effects include:

  • decreased weight
  • decreased appetite
  • nausea and vomiting
  • diarrhea
  • fatigue

Suicidal thoughts and behaviors

Duloxetine carries a boxed warning stating that, like other antidepressants, it may increase the risk of suicidal thoughts and actions in some individuals, particularly young people. People taking duloxetine should be monitored for any worrisome changes in mood, thought patterns, or behavior.

Pregnancy and breastfeeding

Data show that the use of duloxetine during the month before childbirth may increase the risk of postpartum hemorrhage, or heavy bleeding after delivery.

Substantial health problems requiring prolonged hospitalization, respiratory support, and tube feeding have been reported in babies born after exposure to duloxetine during the third trimester of pregnancy.

Duloxetine is secreted in human breast milk, and there have been reports of babies exposed to the medication in breast milk who develop sedation, trouble feeding, and poor weight gain.

The decision of whether or not to use duloxetine during pregnancy or while breastfeeding should be discussed between patients and their healthcare teams, weighing these risks against the potential benefits of treatment.


Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

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