What is the recommended dosage and use of duloxetine (Cymbalta) for various medical conditions?

Duloxetine (Cymbalta): Dosing and Clinical Applications

Duloxetine 60 mg once daily is the standard therapeutic dose for chronic pain conditions including diabetic neuropathy, fibromyalgia, chronic low back pain, and osteoarthritis, with initiation at 30 mg daily for one week to minimize nausea. 1, 2, 3

Standard Dosing Protocol

Start at 30 mg once daily for 1 week, then increase to 60 mg once daily to reduce nausea and improve tolerability 1, 2, 3. This titration strategy significantly decreases the most common adverse effect (nausea) while maintaining efficacy 1.

• The 60 mg daily dose can be given as a single daily dose or split into 30 mg twice daily with equivalent efficacy 1
• Doses above 60 mg daily provide no additional benefit for pain conditions and are less well tolerated 3, 4
• Take with or without food, swallow capsules whole—do not crush, chew, or open 3
• Must be taken daily (not as needed) for continuous effect 2

FDA-Approved Pain Indications

Diabetic Peripheral Neuropathic Pain

• Dose: 60 mg once daily 3
• Provides ≥50% pain reduction with risk ratio of 1.73 (NNT = 5) at 12 weeks 1, 4
• Effectiveness sustained up to one year in open-label trials 1
• First-line medication per American Diabetes Association 1

Fibromyalgia

• Dose: 60 mg once daily 5
• Provides ≥50% pain reduction with risk ratio of 1.57 (NNT = 8) at 12 weeks and sustained at 28 weeks 4
• Improves pain, function, and quality of life with small to moderate benefits 5

Chronic Musculoskeletal Pain

Osteoarthritis (particularly knee):

• Dose: 60 mg once daily 1, 2
• Use when topical NSAIDs are insufficient or multiple joints are affected 5, 1
• More effective in patients >65 years old and specifically for knee osteoarthritis 5, 1
• Small to moderate benefits at 3-6 months and sustained at 6-12 months 5, 1

Chronic Low Back Pain:

• Dose: 60 mg once daily 2
• Consider after insufficient response to nonpharmacologic approaches like exercise 5
• Moderate-quality evidence shows small improvements 5

Special Populations

Elderly Patients (≥65 years)

• Start at 30 mg once daily for 2 weeks before increasing to 60 mg daily 3
• Adverse events may be more severe but can be attenuated with slower titration 1
• Duloxetine is preferred over tricyclic antidepressants due to lack of anticholinergic effects 5

Renal Insufficiency

• Consider lower starting dose with gradual titration 1, 3
• Important consideration since diabetes frequently complicates renal disease 3

Safety Profile

Common Adverse Effects

• Nausea (most common—reduced by starting at 30 mg) 5, 1
• Sedation, dizziness, dry mouth, constipation 5
• 16% discontinuation rate due to adverse effects 4, 6

Cardiovascular Safety

• Does not produce clinically important ECG changes or blood pressure alterations 1, 2
• Safer cardiovascular profile than tricyclic antidepressants 1

Metabolic Considerations

• Small increase in A1C reported in longer-term studies in diabetic patients 1
• Monitor glucose control in diabetic patients 1

Serious Adverse Events

• Rare overall 4, 6
• FDA boxed warning applies (standard for all antidepressants) 5

Discontinuation Protocol

Taper over at least 2-4 weeks for patients treated longer than 3 weeks to avoid withdrawal symptoms 1, 2. Discontinue only after consultation with prescribing provider 2.

Clinical Pearls

• Routine aminotransferase monitoring is generally unnecessary 2
• Pain relief can occur within one week at 60 mg daily 7
• Particularly beneficial for patients with comorbid depression and chronic pain 5
• Do not use with CYP1A2 inhibitors or MAO inhibitors 3
• Use caution with drugs metabolized by CYP2D6 3