Duloxetine: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on Oct 6, 2023.

1. How it works

• Duloxetine may be used for the treatment of depression, chronic pain, or anxiety.
• Experts are unsure exactly how duloxetine works, although historically it was believed that duloxetine’s antidepressant, pain-relieving, and anti-anxiety actions were due to its ability to rebalance chemicals in the brain, such as serotonin and noradrenaline, that were thought to be imbalanced. Studies confirm that duloxetine is still effective, even though the way that it works is unknown.
• Duloxetine belongs to a group of medicines called Selective Serotonin and Norepinephrine Reuptake Inhibitors (SSNRIs).

2. Upsides

• Used in the treatment of moderate-to-severe depression (Major Depressive Disorder).
• May be used to relieve symptoms of anxiety in adults and children aged over 7 years with generalized anxiety disorder.
• May relieve nerve pain associated with diabetes (diabetic peripheral neuropathy).
• May be used to relieve pain associated with fibromyalgia and in the treatment of chronic musculoskeletal pain.
• Duloxetine is available under the brand name Cymbalta.
• Generic duloxetine is available.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Drowsiness, insomnia, nausea, headaches, dry mouth, constipation, and dizziness. Most people experience side effects with duloxetine and one in six people stops taking the drug because of them. Severe skin reactions and urinary retention have also been reported with duloxetine.
• An increased risk of suicidal thoughts, especially in young adults under the age of 24 (similar to other antidepressants).
• Associated with a discontinuation syndrome if stopped abruptly or even when tapered. Symptoms may include anxiety, headache, dizziness, diarrhea, abnormal sensations such as pins and needles, irritability, insomnia, increased sweating, and tiredness. Discontinue slowly on a doctor's advice.
• Interaction or overdosage may cause serotonin syndrome (symptoms include mental status changes [such as agitation, hallucinations, coma, delirium), fast heart rate, dizziness, flushing, muscle tremor or rigidity, and stomach symptoms (including nausea, vomiting, and diarrhea).
• May precipitate a manic episode in people with undiagnosed bipolar disorder.
• May cause a lowering of blood pressure - this may be particularly noticeable when going from a sitting to a standing position. May also increase blood pressure in some people.
• May increase the risk of bleeding; caution when using other drugs that increase bleeding risk (such as aspirin and NSAIDs).
• May cause a lowering of total body sodium (called hyponatremia); elderly people or people taking diuretics or already dehydrated may be more at risk.
• The dosage of duloxetine needs to be reduced in people with mild to moderate kidney or liver disease. Avoid in severe kidney and liver disease. There have been reports of fatal liver failure associated with duloxetine use.
• May worsen blood sugar control in people with diabetes. May trigger an angle-closure attack in people with glaucoma. May not be suitable for people with a history of seizures. May interact with several other drugs including those metabolized by cytochrome p450 2D6 or 1A2 enzymes (such as nortriptyline or flecainide).

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Duloxetine has antidepressant, anti-anxiety, and pain-relieving properties; however, it may cause a discontinuation syndrome on withdrawal even when tapered. Symptoms may include anxiety, headache, dizziness, diarrhea, abnormal sensations such as pins and needles, irritability, insomnia, increased sweating, and tiredness.

5. Tips

• May be taken with or without food.
• Swallow duloxetine capsules whole, do not crush or chew. Do not open the capsule and sprinkle on foods or liquids, as this may affect the way the contents of the capsule are absorbed.
• Dosages of 30 mg/day for at least one week may be desirable initially to allow improved tolerance to the effects of duloxetine. No evidence that dosages greater than 60mg/day offer any additional benefit.
• Get up slowly when going from a lying down or sitting position to standing, because duloxetine may make you feel dizzy.
• Report to your doctor any signs of worsening of depression or suicidal thoughts particularly during the first few months of therapy. Also report any symptoms such as agitation, hallucinations, a fast heart rate, dizziness, flushing, muscle tremor or rigidity, nausea, vomiting, or diarrhea.
• Do not stop suddenly as withdrawal or discontinuation symptoms may occur. Taper off slowly on a doctor's advice.
• Do not drive or operate machinery if duloxetine makes you drowsy or impairs your judgment. Avoid alcohol.
• If your mood changes, depression, or a worsening of depression occurs, or you experience seizures, talk with your doctor.
• Report any problems with bleeding or bruising to your doctor, also report any unexplained skin changes (such as blisters or rashes), problems with urination, eye pain or swelling, and vision changes to your doctor.

6. Response and effectiveness

• May take up to two hours before absorption occurs. Peak concentrations are reached approximately six hours after a dose. Full clinical effects (including relief from depression, anxiety, or pain) may not occur for several weeks.

7. Interactions

Medicines that interact with duloxetine may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with duloxetine. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with duloxetine include:

• anti-anxiety medications, including other benzodiazepines, such as diazepam and oxazepam
• antibiotics such as ciprofloxacin and enoxacin
• anticoagulants such as warfarin
• anticonvulsants such as phenytoin
• antidepressants, such as amitriptyline, imipramine, nortriptyline, and SSRIs (such as fluoxetine and paroxetine)
• antihistamines that cause sedation, such as diphenhydramine
• antiplatelet agents, such as aspirin, apixaban, clopidogrel, and NSAIDs (such as ibuprofen, diclofenac, naproxen)
• aprepitant
• diuretics, such as furosemide
• heartburn medications such as cimetidine, lansoprazole, and omeprazole
• HIV medications such as indinavir and ritonavir
• linezolid
• methylphenidate
• migraine treatments, such as rizatriptan and sumatriptan
• monoamine oxidase inhibitors, such as selegiline, isocarboxazid, or phenelzine
• omega-3 fatty acids
• opioid analgesics such as fentanyl, oxycodone, and morphine
• muscle relaxants such as cyclobenzaprine
• serotonin modulators, such as nefazodone and trazodone
• sleeping pills, such as zolpidem
• some chemotherapy treatments
• some heart medications, such as amiodarone, flecainide, doxazosin, and prazosin
• some medications used to treat mental illness, such as aripiprazole, clozapine, and thioridazine
• any medication that releases serotonin, such as lithium, tramadol, and St John's Wort
• voriconazole.

Alcohol may worsen the side effects of duloxetine such as drowsiness, dizziness, and liver toxicity.

Note that this list is not all-inclusive and includes only common medications that may interact with duloxetine. You should refer to the prescribing information for duloxetine for a complete list of interactions.

References

• Duloxetine. Revised 09/2023. Macleodspharma.com https://www.drugs.com/pro/duloxetine-capsules.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use duloxetine only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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