What are the indications and dosing guidelines for Duloxetine (Cymbalta)?

Indications and Dosing Guidelines for Duloxetine (Cymbalta)

Duloxetine is FDA-approved for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain in adults, with specific dosing recommendations for each condition. 1

FDA-Approved Indications

• Major depressive disorder in adults 1
• Generalized anxiety disorder in adults and pediatric patients 7 years of age and older 1
• Diabetic peripheral neuropathic pain in adults 1
• Fibromyalgia in adults 1
• Chronic musculoskeletal pain in adults (including chronic low back pain and osteoarthritis pain) 1

Dosing Guidelines by Indication

Diabetic Peripheral Neuropathic Pain

• Recommended dose: 60 mg once daily 1
• No evidence that doses higher than 60 mg provide additional benefit 1
• For patients with tolerability concerns, a lower starting dose may be considered 1
• For patients with renal impairment, consider lower starting dose with gradual increase 1
• Duloxetine at 60 mg daily has demonstrated effectiveness with a number needed to treat (NNT) of 5 for achieving ≥50% pain reduction 2

Fibromyalgia

• Recommended dose: 60 mg once daily 1
• Begin treatment at 30 mg once daily for 1 week, then increase to 60 mg once daily 1
• No evidence that doses greater than 60 mg/day provide additional benefit 1
• Effective for fibromyalgia over 12 weeks with NNT of 8 for ≥50% pain reduction 2

Chronic Musculoskeletal Pain (Osteoarthritis and Low Back Pain)

• Recommended dose: 60 mg once daily 3
• For osteoarthritis pain, duloxetine is recommended when pain affects multiple joints or is incompletely controlled with topical NSAIDs 4
• For chronic low back pain, duloxetine can be considered when patients have had insufficient response to nonpharmacologic approaches such as exercise 4

Major Depressive Disorder

• Starting dose: 40 mg/day (given as 20 mg twice daily) to 60 mg/day (given either once daily or as 30 mg twice daily) 1
• For some patients, start at 30 mg once daily for 1 week before increasing to 60 mg once daily 1
• Maximum dose: 120 mg/day (although no evidence that doses >60 mg/day provide additional benefits) 1

Generalized Anxiety Disorder

• Adults <65 years: 60 mg once daily 1
• Consider starting at 30 mg once daily for 1 week before increasing 1
• Geriatric patients: Start at 30 mg once daily for 2 weeks before considering increase to 60 mg/day 1
• Pediatric patients (7-17 years): Start at 30 mg once daily for 2 weeks before considering increase to 60 mg once daily 1
• Recommended range for pediatric patients: 30-60 mg once daily 1

Administration Guidelines

• Administer orally with or without meals 1
• Swallow capsules whole; do not chew, crush, or open the delayed-release capsule 1
• If a dose is missed, take it as soon as remembered; if close to next dose, skip missed dose 1
• Do not take two doses at the same time 1

Discontinuation Guidelines

• Taper duloxetine when discontinuing, especially after treatment longer than 3 weeks, to prevent withdrawal symptoms 5
• Consider the reason for discontinuation when planning the tapering schedule 5

Safety Considerations

• Common adverse effects include nausea, dry mouth, headache, constipation, dizziness, and fatigue 5
• Serious but rare adverse effects may include hepatic failure, severe skin reactions, suicidal thinking, and serotonin syndrome 5
• Approximately 16% of patients discontinue due to adverse effects, though serious adverse events are rare 2
• Duloxetine may interact with drugs metabolized by CYP1A2 and CYP2D6 5, 6
• Significant drug interactions occur with CYP1A2 inhibitors like fluvoxamine (460% increase in duloxetine exposure) 6
• Smoking is associated with a 30% decrease in duloxetine concentration 6

Clinical Pearls

• Starting at a lower dose (30 mg daily) for one week before increasing to the therapeutic dose can improve tolerability and reduce nausea 7
• For painful diabetic neuropathy, duloxetine is considered a first-line treatment at doses of 60-120 mg daily 4, 5
• Duloxetine should not be used in combination with CYP1A2 inhibitors or nonselective, irreversible monoamine oxidase inhibitors 7
• In patients with hepatic impairment or severe renal impairment, dose adjustments or avoidance may be warranted 6
• Pain relief with duloxetine can occur within one week at the 60 mg daily dose 7