What is Cymbalta (duloxetine) used for and what are its potential side effects?

Cymbalta (Duloxetine): Clinical Uses and Side Effects

FDA-Approved Indications

Cymbalta (duloxetine) is FDA-approved for treating major depressive disorder, generalized anxiety disorder (in adults and children ≥7 years), diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain in adults. 1

Primary Clinical Applications

• Neuropathic Pain: Duloxetine 60 mg daily is the only drug studied in a large randomized trial showing moderate clinical benefit for chemotherapy-induced peripheral neuropathy (CIPN), with 59% pain reduction versus 38% with placebo, and is particularly effective for platinum-based therapy-induced neuropathy 2

• Diabetic Neuropathy: The American Diabetes Association recommends duloxetine as first-line treatment for diabetic peripheral neuropathic pain, with sustained efficacy up to one year 3

• Depression and Anxiety: Duloxetine effectively treats major depressive disorder and generalized anxiety disorder, with improvements in both emotional and painful physical symptoms 1, 4

• Fibromyalgia and Chronic Pain: Approved for fibromyalgia and chronic musculoskeletal pain including chronic low back pain and osteoarthritis 5, 1

Dosing and Administration

Start duloxetine at 30 mg once daily for one week, then increase to 60 mg once daily to minimize nausea, which is the most common adverse effect. 3

• Maximum dose: 60 mg twice daily (120 mg/day) 5
• Take with or without food 1
• Swallow capsules whole—do not crush, chew, or open 1
• For maximum pain relief, 60 mg daily is typically required, with 60 mg once daily as effective as 60 mg twice daily 3
• Must be taken daily (not as needed) 3

Common Side Effects

The most frequently reported adverse effects include 1:

• Nausea (most common, can be reduced by starting at 30 mg daily) 3
• Dry mouth
• Sleepiness and fatigue
• Constipation
• Dizziness
• Loss of appetite
• Increased sweating
• Headache

In children and adolescents, monitor height and weight during treatment, as decreased weight is a common side effect. 1

Serious Adverse Effects (Rare but Important)

Life-Threatening Complications

Serotonin syndrome is a life-threatening condition that can occur, especially when combined with other serotonergic medications (SSRIs, SNRIs, MAOIs, triptans, tramadol, fentanyl, amphetamines, or St. John's Wort). 1 Symptoms include:

• Agitation, hallucinations, or mental status changes
• Racing heartbeat, high or low blood pressure
• Muscle rigidity, tremor, or seizures
• Fever, sweating, nausea, vomiting, diarrhea 1

Other Serious Risks

• Liver damage: Monitor for itching, right upper abdominal pain, dark urine, yellow skin/eyes, or increased liver enzymes 1

• Blood pressure changes: May increase blood pressure or cause orthostatic hypotension with dizziness and falls, particularly in elderly patients 1

• Abnormal bleeding: Increased risk when combined with warfarin, NSAIDs, or aspirin 1

• Severe skin reactions: Blisters, peeling rash, mouth sores, or hives requiring immediate medical attention 1

• Hyponatremia: Low sodium levels, especially in elderly patients, causing headache, confusion, weakness, or memory problems 1

• Visual problems: Eye pain, vision changes, or swelling around the eye 1

• Urinary retention: Decreased urine flow or inability to pass urine 1

• Seizures or convulsions 1

• Manic episodes: Increased energy, racing thoughts, reckless behavior, decreased need for sleep 1

Critical Safety Considerations

Discontinuation Syndrome

Never stop duloxetine abruptly—taper over at least 2-4 weeks if treated longer than 3 weeks to avoid withdrawal symptoms. 3, 5 Discontinuation symptoms include:

• Anxiety, irritability
• Insomnia, fatigue
• Headache, dizziness
• Electric shock-like sensations
• Nausea, vomiting, diarrhea
• Sweating 1

Drug Interactions

Avoid combining duloxetine with potent CYP1A2 inhibitors (like ciprofloxacin, enoxacin) and use caution with drugs metabolized by CYP2D6 (propafenone, flecainide, quinidine, thioridazine). 1

Special Populations

• Elderly patients: Higher risk for falls, hyponatremia, and adverse effects; may require lower doses and slower titration 3, 5

• Pregnancy/Breastfeeding: Duloxetine passes into breast milk; discuss risks and benefits with healthcare provider 1

• Alcohol: Avoid heavy alcohol use due to risk of severe liver injury 1

• Diabetes: Small increase in A1C reported in longer-term studies 3

Regulatory Status

Duloxetine is not a controlled substance and does not appear in DEA schedules I-V, as it lacks significant abuse liability. 5