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Cymbalta is an antidepressant approved to treat mood and pain disorders. It was one of Eli Lilly’s most profitable drugs. It works by preventing the body from reabsorbing two neurotransmitters: serotonin and norepinephrine. The drug has a long list of interactions, and possible side effects include nausea, increased sweating and withdrawal symptoms.

Last Modified: September 5, 2023
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Cymbalta comes in delayed-release capsules and is a part of a drug class called serotonin and norepinephrine reuptake inhibitors, or SNRIs. Eli Lilly and Company manufactures the medication. Duloxetine is the drug’s active ingredient.

The U.S. Food and Drug Administration first approved the antidepressant in 2004. The drug quickly grew in popularity. In 2009 alone, doctors wrote 14.6 million prescriptions, according to The New York Times.

At its peak in 2012, the drug had annual sales of $4.99 billion, according to Indy Star. The drug’s patent ran out in 2013, opening the door to several generic manufacturers.

A Sept. 30, 2018 quarterly filing with the Securities and Exchange Commission reported Cymbalta had brought in $523.5 million worldwide in nine months for the drug maker in 2018, including $39.3 million in the United States.

Depending on the dose strength, the medication can cost anywhere between $242.73 and $472.66 for a 30-day supply, according to Drugs.com. One 2022 research report noted that, for chemotherapy-induced peripheral neuropathy, costs of duloxetine varied from $12 (generic) to $529 (brand name).

Uses, Dosages and Strengths

The FDA originally approved Cymbalta for major depressive disorder and generalized anxiety disorder. The agency has since approved the medication for diabetic peripheral neuropathic pain, fibromyalgia and chronic musculoskeletal pain in adults. The drug is not approved for use in children and teens.

Eli Lilly had tried to get the drug approved for stress urinary incontinence as well. But the FDA suggested it could not grant approval based on the data the company had provided, so the drug maker withdrew its application in 2005, according to a company press release.

Then, the company began investigating duloxetine to treat children with fibromyalgia. It updated its Phase III clinical trial progress on Aug. 14, 2018 on ClinicalTrials.gov. Eli Lilly researcher Dr. Himanshu P. Upadhyaya and colleagues presented the study results at the 2018 World Congress on Pain in Boston. They concluded duloxetine may not be effective in treating juvenile primary fibromyalgia syndrome compared to a placebo.

Depending on the treatment indication and the patient’s age, doctors may prescribe different strengths. The medication comes in 20 mg, 30 mg and 60 mg delayed-release capsules.

Cymbalta 20mg capsule
Cymbalta 20mg capsule
Cymbalta 30mg capsule
Cymbalta 30mg capsule
Cymbalta 60mg capsule
Cymbalta 60mg capsule
Major Depressive Disorder:
40 mg to 60 mg a day. The maximum dose is 120 mg a day.
Generalized Anxiety Disorder:
60 mg a day. The maximum dose is 120 mg a day.
Diabetic Peripheral Neuropathic Pain:
60 mg a day. The maximum dose is 60 mg a day.
30 mg a day. The maximum dose is 60 mg a day.
Chronic Musculoskeletal Pain:
30 mg a day. The maximum dose is 60mg a day.

Patients should swallow capsules whole with or without food. If patients miss a dose, they should take the missed dose as soon as possible, but they should not take two doses at the same time.


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How Duloxetine Works

Researchers believe duloxetine works by increasing the activity of serotonin and norepinephrine in the central nervous system, according to the drug’s label.

The National Institutes of Health says duloxetine increases the levels of the neurotransmitters in the brain by preventing the body from reabsorbing them, and this contributes to its antidepressant effects.

Neurotransmitters diagram
Researchers believe blocking the reabsorption of neurotransmitters can reduce symptoms of depression.

Depression, chronic pain and anxiety have inter-related symptoms, according to researcher Cheryl L. Wright and fellow researchers at the Oregon Health and Science University School of Nursing. Researchers believe duloxetine treats general pain disorder, diabetic peripheral neuropathic pain and fibromyalgia in the same way it treats depression and anxiety.

Researchers know the drug does not repair the nerve damage that leads to diabetic peripheral neuropathy, but clinical trials have shown the drug can relieve the pain and other sensations associated with the condition, according to an Eli Lilly statement.

“While additional nonindustry-sponsored investigation is warranted, the evidence to date suggests that in those with [fibromyalgia], duloxetine has largely been a safe and, in some, a promising intervention to manage chronic pain.”

Adjusting the levels of neurotransmitters can also relieve fibromyalgia pain without affecting mood, Wright and colleagues wrote in Expert Review of Clinical Immunology.

“While additional nonindustry-sponsored investigation is warranted, the evidence to date suggests that in those with [fibromyalgia], duloxetine has largely been a safe and, in some, a promising intervention to manage chronic pain,” the researchers wrote. “As with the introduction of any new pharmacologic agent, each patient deserves close monitoring to assess the drug’s effectiveness as well as adverse effects.”

Side Effects

Five percent or more of the people who had taken Cymbalta during clinical trials reported common side effects at least twice as often as those who had taken a placebo. According to the drug’s label, the most common side effects of Cymbalta were nausea, dry mouth, sleepiness, constipation, loss of appetite and increased sweating.

Though rare, serious side effects can include life-threatening conditions, and the FDA has released several warnings for side effects such as liver disease and low blood pressure. The medication carries a black box warning for suicidal thoughts and behaviors in children, adolescents and young adults.

Patients should talk to their doctor as soon as they notice any changes in their condition. Many side effects will simply work themselves out in time, but a doctor may need to adjust the medication dosage.

Never stop taking duloxetine suddenly or without first consulting a doctor, even if you experience side effects. Stopping the medication abruptly can trigger withdrawal symptoms, including dizziness, headache, nausea, diarrhea, tingling sensation, irritability, vomiting, insomnia, anxiety, increased sweating and fatigue.

The medication insert recommends doctors gradually reduce the dose rather than suddenly stopping treatment. Some people who say they suffered withdrawal side effects filed lawsuits against Eli Lilly.

Food, Alcohol and Drug Interactions

Medications that may interact with Cymbalta range from over-the-counter pain relievers to prescription blood pressure medicines, according to Everyday Health. The drug’s label has a long list of possible interactions.

Taking duloxetine with certain other drugs can affect serotonin levels, blood pressure and body temperature. It can lead to a life-threatening condition called serotonin syndrome.

Symptoms of serotonin syndrome can include agitation, confusion, diarrhea and dilated pupils. Other signs to look for are elevated blood pressure, heavy sweating and rapid heart rate. The condition can also cause muscles to be rigid or twitch.

Did You Know?
Smoking decreases Cymbalta’s concentration in the blood by 30 percent.

Mixing Cymbalta with grapefruit or grapefruit juice may increase the risk of side effects or overdose. The acidic fruit interferes with the metabolism of the drug and may allow it to build up in the patient.

Light drinking of alcohol does not appear to enhance duloxetine’s effects. But heavy alcohol drinking can contribute to liver stress or damage.

Drugs and substances that may interact with Cymbalta include:

  • MAO Inhibitors (Nardil, Parnate, others)
  • SSRIs (Celexa, Fluvoxamine, Lexapro, Prozac, Paxil, Symbyax, Zoloft)
  • Triptans (Amerge, Axert, Frova, Imitrex, Masalt, Replax, Zomig)
  • Other SNRIs (Pristiq, Fetzima, Ixel, Savella, Elamol, Tofacine, Effexor)
  • Tricyclic antidepressants (Anafranil, Ascendin, Norpramin, Sinequan)
  • Aminoketones (Wellbutrin)
  • Fluoroquinolone antibiotics (Cipro, Levaquin, Avelox)
  • St. John’s Wort
  • NSAIDs such as ibuprofen
  • Aspirin
  • Warfarin
  • Drugs that affect gastric acidity
  • Caffeine

This is not a complete list of all food and drug interactions. Patients should talk with their doctors about any drugs or supplements they are taking as well as alcohol use and diet to make sure they are not exposed to a potential interaction.

Before You Take Cymbalta

Some complications can be prevented if patients have an honest discussion with their doctors before starting treatment. This will also ensure patients receive the most effective treatment the drug can deliver.

The National Alliance on Mental Illness recommends people discuss the following issues with their doctors:
  • The most bothersome symptoms
  • Thoughts of harming themselves
  • Previous medicines taken for their condition
  • How effective other medicines were or if they caused any side effects
  • Other mental or physical health conditions including bipolar disorder, kidney or liver disease
  • Other medications the patient is taking including over-the-counter drugs and supplements
  • Allergies to any medications
  • Other mental health treatment such as talk or substance therapy
  • Current or planned pregnancy or breastfeeding
  • Alcohol or drug use

Misleading Ads

The FDA has repeatedly reprimanded Eli Lilly for running misleading ads that overstate the benefits of Cymbalta while downplaying the risks.

In 2005, the FDA said Eli Lilly had run ads in a medical journal that were misleading because they failed to disclose important risks and side effects, Pharma Times reported.

Then, in 2007, the FDA called out the company for using a professional mailer that “overstates the efficacy of Cymbalta and omits some of the most serious and important risk information associated with its use.”

Eli Lilly suggested patients with diabetic peripheral neuropathy “experienced significantly less pain interference with overall functioning” but there was no evidence the claim was true, the FDA said in letter to the company.

In an ad in the WebMD Little Blue Book of Rheumatology, the drug maker claimed patients with fibromyalgia could achieve a 30 percent improvement in pain after taking Cymbalta, MedCity News reported. The FDA said in 2010 that no data existed to support the claim.

In all these cases, the FDA ordered Eli Lilly to stop the ad campaigns.


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