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

Duloxetine: Indications and Dosing Guidelines

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

FDA-Approved Indications

Duloxetine is indicated for treatment of: 1

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

Standard Dosing Regimens

Major Depressive Disorder

• Starting dose: 40 mg/day (20 mg twice daily) to 60 mg/day (once daily or 30 mg twice daily) 1
• Alternative initiation: 30 mg once daily for 1 week to improve tolerability, then increase to 60 mg once daily 1
• Maximum dose: 120 mg/day, though no evidence supports additional benefit beyond 60 mg/day 1

Generalized Anxiety Disorder

Adults <65 years:

• Starting dose: 60 mg once daily 1
• Alternative initiation: 30 mg once daily for 1 week, then 60 mg once daily 1
• Dose escalation: If needed, increase in 30 mg increments; maximum studied dose 120 mg/day 1

Geriatric patients (≥65 years):

• Starting dose: 30 mg once daily for 2 weeks before increasing to 60 mg/day 1
• Dose escalation: May increase beyond 60 mg in 30 mg increments if needed; maximum 120 mg/day 1

Pediatric patients (7-17 years):

• Starting dose: 30 mg once daily for 2 weeks 1
• Target dose: 60 mg once daily (range 30-60 mg/day) 1
• Dose escalation: If needed, increase in 30 mg increments; maximum studied dose 120 mg/day 1

Diabetic Peripheral Neuropathic Pain

• Standard dose: 60 mg once daily 1
• No evidence supports doses >60 mg/day, and higher doses are less well tolerated 1
• For tolerability concerns: Consider lower starting dose 1
• Renal impairment: Use lower starting dose with gradual titration 1
• Efficacy data: Approximately 50% of patients achieve ≥50% pain reduction at 12 weeks; NNT 4.9 for 120 mg/day and 5.2 for 60 mg/day 2

Fibromyalgia

• Starting dose: 30 mg once daily for 1 week 1
• Target dose: 60 mg once daily 1
• Maximum dose: 60 mg/day; no additional benefit with 120 mg/day, and higher doses increase adverse events 1
• Response: Some patients respond to 30 mg/day starting dose 1

Chronic Musculoskeletal Pain (Osteoarthritis and Low Back Pain)

According to CDC guidelines:

• Osteoarthritis: Use duloxetine when topical NSAIDs are insufficient or when systemic NSAIDs are contraindicated 3
• Chronic low back pain: Consider duloxetine after insufficient response to nonpharmacologic approaches like exercise 3

Dosing per FDA label:

• Starting dose: 30 mg once daily for 1 week 2, 4
• Target dose: 60 mg once daily 2
• Dose escalation: May increase to 120 mg daily if suboptimal response after 7 weeks at 60 mg 2

Administration Guidelines

• Take with or without food 1
• Swallow capsules whole—do not chew, crush, open, or mix contents with food/liquids 1
• Missed dose: Take as soon as remembered unless almost time for next dose; never double dose 1
• Timing: Can be taken at any time of day 2

Dose Escalation Strategy

When increasing doses beyond initial target: 2, 4

• Escalate in 30 mg increments
• Allow at least 1-2 weeks at each dose level to assess response
• Maximum dose studied: 120 mg/day
• Older adults require slower titration with cautious increments 4

Special Population Considerations

Renal Impairment

• Not recommended for creatinine clearance <30 mL/min 4
• Use lower starting dose with gradual titration in diabetic patients (frequently complicated by renal disease) 1

Hepatic Impairment

• Dose reduction required 4

Older Adults

• Start with lower doses and use slower titration 4
• Increased risk of adverse effects including cognitive impairment, falls, and drug-drug interactions 2

Monitoring Requirements

• Blood pressure monitoring: Duloxetine can cause modest hypertension 4
• Assess adverse effects at each follow-up visit, particularly with higher doses 4
• Evaluate therapeutic response using standardized pain or depression scales 4
• Weekly contact during titration phase recommended 2
• Monthly follow-up until symptoms stabilized 2
• Watch for mood changes, particularly in young adults during first few months 4

Discontinuation Protocol

Taper gradually over at least 2-4 weeks when discontinuing after >3 weeks of treatment 2, 4

Slower taper approach for high-risk patients: 4

• Consider 3-4 weeks with smaller decrements (e.g., 120→100→80→60 mg)
• Use for patients with history of withdrawal symptoms
• Allow at least one week at each dose level

Common withdrawal symptoms: Nausea, dizziness 5

Common Adverse Effects

Most frequent (dose-dependent): 2, 5

• Nausea (most common—reduced by starting at 30 mg/day) 6
• Dry mouth
• Headache
• Constipation
• Dizziness
• Decreased appetite
• Somnolence/fatigue

Serious but rare: 2

• Hepatic failure
• Severe skin reactions
• Suicidal thinking and behavior
• Serotonin syndrome

Discontinuation rate: Approximately 16% stop due to adverse effects 7

Drug Interactions

• CYP1A2 inhibitors: Avoid concomitant use 2
• CYP2D6 substrates: Use caution, particularly with narrow therapeutic index drugs 2
• MAO inhibitors: Contraindicated 6
• NSAIDs: When combining, use caution in patients with cardiovascular comorbidities (duloxetine can increase blood pressure and heart rate) 2

Evidence-Based Efficacy by Condition

Diabetic Neuropathy

• Moderate-quality evidence for 60 mg and 120 mg daily (not lower doses) 3
• RR for ≥50% pain reduction at 12 weeks: 1.73 (95% CI 1.44-2.08); NNT: 5 7

Fibromyalgia

• RR for ≥50% pain reduction at 12 weeks: 1.57 (95% CI 1.20-2.06); NNT: 8 7
• Effect may be greater in patients with comorbid depression 2

Chronic Low Back Pain

• Moderate-quality evidence demonstrates small improvements 3

Osteoarthritis

• Moderate to high strength evidence supports use, particularly when NSAIDs contraindicated or ineffective 2
• Only centrally acting agent with adequate evidence for OA 2

Clinical Decision Algorithm

If no response after 4-8 weeks at 120 mg once daily: 2

• Switch to different medication class rather than further dose increases
• Alternative options: pregabalin, gabapentin, or alternative antidepressants

For chemotherapy-induced peripheral neuropathy: 4

• 30 mg daily for 1 week, then 60 mg daily
• Better response in cisplatin-treated than taxane-treated patients