What is the proper dosing and usage of Cymbalta (duloxetine) for various conditions?

Proper Dosing and Usage of Cymbalta (Duloxetine) for Various Conditions

Duloxetine should be administered at 60 mg once daily for most conditions, with lower starting doses of 30 mg daily for 1-2 weeks recommended to improve tolerability. 1

General Administration Guidelines

• Administer duloxetine orally with or without food, and swallow capsules whole - do not chew, crush, or open the delayed-release capsules as this affects the enteric coating 1
• If a dose is missed, take it as soon as remembered; if close to next dose, skip the missed dose and take the next scheduled dose (never take two doses at once) 1
• When discontinuing duloxetine, taper gradually rather than stopping abruptly to minimize withdrawal symptoms such as dizziness, headache, nausea, paresthesia, irritability, and anxiety 1

Condition-Specific Dosing

Major Depressive Disorder (MDD)

• Starting dose: 40-60 mg/day (given as 20 mg twice daily or 60 mg once daily) 1
• For some patients, start at 30 mg once daily for 1 week before increasing to 60 mg daily 1
• While 120 mg/day has shown effectiveness, no evidence supports additional benefits beyond 60 mg/day 1

Generalized Anxiety Disorder (GAD)

• Adults under 65: Start with 60 mg once daily; may start at 30 mg once daily for 1 week if tolerability is a concern 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
• Maximum studied dose was 120 mg per day, but no evidence supports additional benefits beyond 60 mg/day 1, 2

Diabetic Peripheral Neuropathic Pain

• Standard dose: 60 mg once daily 1
• No evidence supports that doses higher than 60 mg once daily provide additional significant benefit, and higher doses are less well tolerated 1, 3
• For patients with tolerability concerns, consider a lower starting dose 1
• For patients with renal impairment, use a lower starting dose and gradually increase 1

Fibromyalgia

• Recommended dose: 60 mg once daily 1
• Begin with 30 mg once daily for 1 week before increasing to 60 mg once daily 1
• Higher doses do not confer additional benefits but increase adverse reactions 1, 3
• Duloxetine has shown effectiveness for fibromyalgia with an NNT of 8 for ≥50% pain reduction 3

Chronic Musculoskeletal Pain

• Recommended dose: 60 mg once daily 1
• Begin with 30 mg once daily for 1 week before increasing to 60 mg once daily 1
• No evidence supports higher doses providing additional benefit 1

Cancer-Related Neuropathic Pain

• Starting dose: 30-60 mg daily; increase to 60-120 mg daily as needed 4
• Used as a coanalgesic in combination with opioids for neuropathic pain components 4

Special Populations and Considerations

Hepatic and Renal Impairment

• Avoid use in patients with chronic liver disease or cirrhosis 1
• Avoid use in patients with severe renal impairment (GFR <30 mL/minute) 1
• For patients with diabetes and renal disease, consider lower starting dosage with gradual increases 1

Drug Interactions

• Allow at least 14 days between discontinuing an MAOI and starting duloxetine 1
• Allow at least 5 days after stopping duloxetine before starting an MAOI 1
• Duloxetine is a moderate inhibitor of CYP2D6 - use with caution in patients taking medications metabolized by this enzyme 2

Monitoring and Adverse Effects

• Common adverse effects include nausea, dry mouth, headache, constipation, dizziness, and fatigue 2
• Monitor for adverse effects at each follow-up visit, particularly those related to higher doses 5
• Monitor blood pressure as duloxetine can cause modest hypertension 5
• Approximately 16% of patients may discontinue treatment due to adverse effects, though serious adverse events are rare 3, 6

Treatment Duration and Assessment

• Periodically reassess to determine the continued need for maintenance treatment 1
• Evaluate therapeutic response using standardized pain or depression scales 5
• For treatment-resistant cases, consider augmentation with another medication class (e.g., pregabalin or gabapentin for neuropathic pain) 5

Common Pitfalls and Caveats

• Duloxetine's analgesic effect is not dependent on its antidepressant activity and may occur at lower doses than needed for depression 4
• When discontinuing, taper gradually to minimize withdrawal symptoms 1
• Patients with concurrent depression and chronic pain may especially benefit from duloxetine 4
• Doses above 60 mg daily rarely provide additional benefits for most conditions but increase the risk of adverse effects 1, 3