What is the recommended dosage of duloxetine (Cymbalta) for adults with depression, anxiety, or chronic pain, considering factors such as impaired renal or liver function?

Duloxetine Dosing Recommendations

Standard Dosing for Depression

For major depressive disorder in adults, start duloxetine at 30 mg once daily for 1 week to minimize nausea, then increase to the target dose of 60 mg once daily. 1

• The FDA-approved starting dosage is 40 mg/day (20 mg twice daily) to 60 mg/day, but initiating at 30 mg once daily for 1 week allows better tolerability before advancing to 60 mg once daily 1
• The maximum studied dose is 120 mg/day, but there is no evidence that doses above 60 mg/day provide additional benefit for depression 1
• Nausea is the most common side effect and occurs less frequently when treatment begins at 30 mg/day with gradual titration 2

Dosing for Generalized Anxiety Disorder

For adults under 65 years with anxiety, initiate at 30 mg once daily for 1 week, then increase to 60 mg once daily. 1

• While 60 mg once daily can be started immediately, beginning at 30 mg improves tolerability 1
• Doses up to 120 mg once daily have been studied, but evidence does not support routine use above 60 mg/day 1
• For geriatric patients (≥65 years), start at 30 mg once daily for 2 weeks before considering increase to 60 mg/day 1

Dosing for Chronic Pain Conditions

Diabetic Peripheral Neuropathy

Administer 60 mg once daily for diabetic neuropathy; this is the only dose with proven efficacy. 1

• There is no evidence that doses higher than 60 mg once daily provide additional benefit, and higher doses are clearly less well tolerated 1
• For patients with tolerability concerns, consider a lower starting dose with gradual titration 1
• The number needed to treat (NNT) for 50% pain reduction is 4.9 for 120 mg/day and 5.2 for 60 mg/day, indicating minimal advantage of higher doses 3
• Since diabetes frequently involves renal complications, use a lower starting dose and gradual increase in patients with renal impairment 1

Fibromyalgia

Begin at 30 mg once daily for 1 week, then increase to 60 mg once daily for fibromyalgia. 1

• Some patients respond to the 30 mg starting dose 1
• Doses greater than 60 mg/day show no additional benefit and are associated with higher adverse event rates 1
• The NNT for fibromyalgia is 8, indicating moderate efficacy 4

Chronic Musculoskeletal Pain (Osteoarthritis and Low Back Pain)

Start at 30 mg once daily for 1 week, then increase to 60 mg once daily for chronic musculoskeletal pain. 1

• Higher dosages do not confer additional benefit, even in non-responders to 60 mg daily 1
• Duloxetine shows small to moderate benefits for osteoarthritis pain at 60 mg daily, with evidence it is more effective in patients over 65 years and those with knee osteoarthritis 3
• For chronic low back pain, duloxetine 60 mg daily demonstrates small improvements when nonpharmacologic approaches are insufficient 3

Special Population Considerations

Hepatic Impairment

Avoid duloxetine entirely in patients with chronic liver disease or cirrhosis. 1

• Duloxetine is contraindicated in severe hepatic impairment 3
• Monitor for signs of hepatic failure including abdominal pain, hepatomegaly, elevated transaminases, or jaundice 5

Renal Impairment

Avoid duloxetine in patients with severe renal impairment (GFR <30 mL/minute). 1

• Increased plasma concentrations of duloxetine and its metabolites occur in end-stage renal disease 1
• For diabetic patients with mild-to-moderate renal impairment, use a lower starting dose with gradual titration 1

Geriatric Patients

In elderly patients with anxiety, start at 30 mg once daily for 2 weeks before increasing to 60 mg/day. 1

• Geriatric patients may be at greater risk for hyponatremia with duloxetine 1
• Lower starting doses and slower titration are appropriate in older adults 3

Critical Safety Monitoring

Cardiovascular Effects

Monitor blood pressure and pulse regularly, as duloxetine can cause sustained increases in both parameters. 5

• Duloxetine combined with other QT-prolonging medications requires monitoring for additive QT prolongation risk, particularly in patients over 65 years, females, those with bradycardia, cardiovascular disease, or electrolyte abnormalities 5
• Avoid combining duloxetine with other serotonergic medications due to serotonin syndrome risk 5

Common Adverse Effects

Nausea, dry mouth, dizziness, constipation, and somnolence are the most frequent side effects, typically mild to moderate and transient. 3

• Starting at 30 mg for 1 week before increasing to 60 mg significantly reduces nausea incidence 5, 2
• Discontinuation rates due to adverse events are approximately 16% across all indications 4
• Most adverse events occur during initial dosing at 60 mg; subsequent dose escalations produce few additional adverse effects 6

Discontinuation Protocol

Taper duloxetine gradually rather than stopping abruptly to minimize withdrawal symptoms. 1

• Withdrawal symptoms include dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue 1

Administration Guidelines

Swallow duloxetine capsules whole with or without food; do not chew, crush, or open capsules. 1

• The enteric coating protects duloxetine from degradation in acidic conditions 1
• If a dose is missed, take it as soon as remembered unless it is almost time for the next dose; never double dose 1

Drug Interactions

Allow at least 14 days between discontinuing an MAOI and starting duloxetine, and at least 5 days after stopping duloxetine before starting an MAOI. 1

• Do not combine duloxetine with CYP1A2 inhibitors or nonselective MAOIs 2
• Exercise caution with drugs metabolized by CYP1A2 and CYP2D6 5