Duloxetine (Cymbalta): Indications and Dosing Guidelines
Duloxetine is FDA-approved for the treatment of major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain in adults. 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, 2
Dosing Guidelines by Indication
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, starting at 30 mg once daily for 1 week may help with adjustment 1
- Maximum effective dose: 60 mg/day (doses up to 120 mg/day have been studied but show no additional benefit) 1
Generalized Anxiety Disorder
- Adults <65 years: 60 mg once daily 1
- Consider starting at 30 mg once daily for 1 week before increasing to 60 mg 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
Diabetic Peripheral Neuropathic Pain
- Standard dose: 60 mg once daily 1
- No evidence that doses higher than 60 mg provide additional benefit 1, 3
- Lower starting dose may be considered for patients with tolerability concerns 1
- For patients with renal impairment, consider lower starting dose with gradual increase 1
Fibromyalgia
- Recommended dose: 60 mg once daily 1
- Start at 30 mg once daily for 1 week before increasing to 60 mg once daily 1
- No evidence that doses greater than 60 mg/day provide additional benefit 1, 3
Chronic Musculoskeletal Pain
- For chronic low back pain and osteoarthritis pain: 60 mg once daily 2, 4
- Start at 30 mg once daily for 1 week before increasing to 60 mg once daily 4
Administration Guidelines
- Administer orally with or without meals 1
- Swallow capsules whole; do not chew, crush, open, or sprinkle contents 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
Special Populations and Considerations
Renal Impairment
- Consider lower starting dose and gradual increase, especially in diabetic patients who often have concurrent renal disease 1
Hepatic Impairment
- Use with caution in patients with hepatic impairment 5
Elderly Patients
- For GAD: Start at 30 mg once daily for 2 weeks before considering increase 1
- Use caution when increasing doses in elderly patients 2
Common Adverse Effects
- Most common: nausea, dry mouth, headache, constipation, dizziness, and fatigue 2, 6
- Nausea is most common but occurs less frequently if treatment is initiated at 30 mg daily and titrated after one week to 60 mg daily 6
- Approximately 16% of patients discontinue due to adverse effects 3, 7
Drug Interactions
- Avoid use with CYP1A2 inhibitors (e.g., fluvoxamine) which can increase duloxetine exposure by 460% 5
- Avoid use with nonselective, irreversible monoamine oxidase inhibitors 6
- Duloxetine may increase exposure of drugs metabolized by CYP2D6 5
- Smoking may decrease duloxetine concentration by approximately 30% 5
Clinical Pearls
- Pain relief in diabetic neuropathy may begin within one week at the 60 mg/day dose 6
- For most pain conditions, the number needed to treat (NNT) for 50% pain reduction ranges from 5-8 3, 7
- When discontinuing duloxetine, taper gradually to prevent withdrawal symptoms, especially after treatment longer than 3 weeks 2
- Duloxetine offers the advantage of treating both pain and comorbid depression/anxiety when present 4