Duloxetine (Cymbalta) Patient Guide: Benefits, Dosing, and Side Effects Explained

This guide is adapted from the clinician guide authored by Sebastián Malleza, M.D., M.Sc. at the Psychopharmacology Institute. For the complete clinical resource, visit: Duloxetine Guide: Pharmacology, Indications, Dosing Guidelines and Adverse Effects

What is Duloxetine?

Duloxetine (brand name Cymbalta) is a medication that treats several conditions including depression, anxiety, and certain types of chronic pain. It belongs to a group of medications called SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors). Duloxetine is particularly helpful for people who have both depression and pain conditions[1].

How Does This Medication Work?

Duloxetine works by increasing the levels of two important brain chemicals called serotonin and norepinephrine[1]. These chemicals help regulate mood, energy levels, and how your body perceives pain.

This dual action makes it useful for treating not only depression and anxiety but also conditions like diabetic nerve pain, fibromyalgia, and chronic muscle pain.

What Conditions Can Duloxetine Treat?

Duloxetine is FDA-approved to treat:

• Major depressive disorder (MDD)[6,7]
• Generalized anxiety disorder (GAD)[10,11]
• Diabetic peripheral neuropathy (nerve pain related to diabetes)[12]
• Fibromyalgia (widespread pain and tenderness)[13,14]
• Chronic musculoskeletal pain (such as chronic low back pain and osteoarthritis pain)[17,18,19]

Some doctors may also prescribe duloxetine for other conditions, including:

• Chemotherapy-induced peripheral neuropathy (nerve pain from cancer treatment)[3,25]
• Stress urinary incontinence (leaking urine during physical activity or when coughing, sneezing, etc.)[26,27]

How to Take This Medication

Duloxetine comes as a delayed-release capsule that you take by mouth. It’s available in several strengths: 20 mg, 30 mg, 40 mg, and 60 mg.

General dosing guidelines:

For depression and anxiety:

• Starting dose: Usually 30 mg once daily for one week, then increasing to 60 mg once daily
• Some people may start directly at 60 mg once daily
• Maximum dose: 120 mg daily

For pain conditions (diabetic nerve pain, fibromyalgia, chronic musculoskeletal pain):

• Starting dose: Usually 30 mg once daily for one week
• Target dose: 60 mg once daily
• Maximum dose: Usually 60 mg daily (higher doses generally don’t provide additional benefit for pain)

Important instructions:

• Swallow the capsule whole with water. Do not crush, chew, or open the capsule[8]
• You can take duloxetine with or without food, but taking it with food may help reduce stomach upset
• Take it at approximately the same time each day
• If you miss a dose, take it as soon as you remember. If it’s almost time for your next dose, skip the missed dose and continue with your regular schedule. Do not take two doses to make up for a missed one
• For those who have difficulty swallowing capsules, a sprinkle form (Drizalma Sprinkle) is available that can be opened and sprinkled on applesauce

Common Side Effects

Many side effects improve over time as your body adjusts to the medication. Common side effects include:

Digestive system effects:

• Nausea (occurs in about 20% of people)[8]
  • Taking with food and ginger supplements may help reduce nausea[28]
• Dry mouth (15%)[8]
• Constipation (11%)[8]

Other common side effects:

• Dizziness (9%)[8]
• Excessive sweating (7%)[8,33]
• Fatigue or drowsiness (8%)[8]
• Insomnia or sleep problems (10%)[8]
• Sexual effects (more common in males, particularly difficulty with orgasm/ejaculation)[8,32]

Duloxetine typically causes minimal weight changes, with studies showing an average weight gain of about 1 kg (2.2 pounds) over a year of treatment[29].

Important Safety Information

Do Not Take Duloxetine If:

• You are taking or have recently taken (within 14 days) medications called MAOIs (monoamine oxidase inhibitors)[8]
• You have liver disease or chronic liver problems[8,34]
• You regularly drink large amounts of alcohol[8,34]
• You have uncontrolled narrow-angle glaucoma[39,40]

Talk to Your Doctor Before Taking Duloxetine If You Have:

• Kidney problems[4]
• High blood pressure or heart problems
• History of seizures
• Bipolar disorder
• Bleeding problems or if you take blood thinners[35,36]
• Low sodium levels[37]
• Glaucoma (increased pressure in the eye)[39,40]
• If you are pregnant, planning to become pregnant, or breastfeeding[45,46,47,48,49]

Avoid While Taking Duloxetine:

• Alcohol (can increase the risk of liver problems)[8,34]
• Other medications that increase serotonin levels without talking to your doctor first
• Driving or operating machinery until you know how this medication affects you

When to Contact Your Doctor Immediately

Contact your healthcare provider right away if you experience:

• Unusual changes in behavior, thoughts of suicide, or worsening depression
• Signs of serotonin syndrome: agitation, hallucinations, rapid heart rate, fever, excessive sweating, shivering, muscle stiffness or twitching, trouble with coordination, nausea, vomiting, or diarrhea[8,41]
• Signs of liver problems: yellowing of the skin or whites of the eyes, dark urine, right-sided abdominal pain, unexplained flu-like symptoms[34]
• Unusual bleeding or bruising[35,36]
• Visual changes or eye pain[39,40]
• Severe allergic reaction: rash, itching, swelling, severe dizziness, trouble breathing
• Symptoms of low sodium: headache, difficulty concentrating, memory problems, confusion, weakness, unsteadiness[37]

Starting and Stopping the Medication

Starting: It may take several weeks (usually 2-4 weeks) before you notice the full benefits of this medication for depression or anxiety. Pain relief may begin sooner.

Stopping: Do not stop taking duloxetine suddenly without talking to your doctor. A gradual reduction in dose over 2-4 weeks is typically recommended to reduce the risk of discontinuation symptoms[30,31].

Possible discontinuation symptoms include:

• Dizziness
• Nausea
• Headache
• Irritability
• Tingling sensations
• Insomnia

Special Considerations

Pregnancy and Breastfeeding

• Limited information is available about the safety of duloxetine during pregnancy
• Some studies show a potential increased risk for urinary tract defects in babies exposed to duloxetine during pregnancy[46]
• There may be an increased risk of postpartum bleeding with SNRIs including duloxetine[47]
• Duloxetine passes into breast milk in small amounts. Most studies show minimal risk to breastfed infants[48,49,52,53]
• Always discuss the risks and benefits with your doctor if you are pregnant or breastfeeding

Older Adults

• No special dosage adjustments are needed for older adults based solely on age[8]
• Starting at lower doses (20-30 mg) may be recommended
• Older adults should be monitored more closely for side effects, particularly low sodium levels[37]

Kidney Problems

• For mild to moderate kidney problems, no dosage adjustment is usually needed
• For severe kidney problems, a lower dose may be recommended[4]

Interactions with Other Medications

Duloxetine can interact with several medications:

• Fluvoxamine, ciprofloxacin, and other CYP1A2 inhibitors can significantly increase duloxetine levels[5]
• Duloxetine can increase levels of other medications like:
  • Some antidepressants (tricyclic antidepressants, paroxetine, fluoxetine)
  • Some antipsychotics (aripiprazole, risperidone)
• Blood thinners (increased bleeding risk)[35,36]
• NSAIDs like ibuprofen or naproxen (increased bleeding risk)[35]

Always tell your doctor and pharmacist about all medications you’re taking, including prescription drugs, over-the-counter medications, and supplements.

References

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Disclaimer: This guide is for general informational purposes and is not a substitute for professional medical advice. Always discuss any questions about your medication with your healthcare provider.