What is the recommended dosing for Cymbalta (duloxetine)?

Cymbalta (Duloxetine) Dosing

Start duloxetine at 30 mg once daily for 1 week, then increase to the therapeutic dose of 60 mg once daily for most indications, which significantly reduces treatment-emergent nausea while producing only a transient delay in therapeutic effect. 1, 2, 3

Standard Dosing by Indication

Generalized Anxiety Disorder (Adults <65 years)

• Initial: 30 mg once daily for 1 week 3
• Target: 60 mg once daily 3
• Maximum: 120 mg once daily (though no evidence that doses >60 mg confer additional benefit) 3
• If increasing beyond 60 mg, use increments of 30 mg once daily 3

Diabetic Peripheral Neuropathic Pain

• Standard dose: 60 mg once daily 3
• For tolerability concerns: May start at 30 mg daily 3
• No evidence that doses >60 mg provide additional benefit and higher doses are less well tolerated 3

Fibromyalgia

• Initial: 30 mg once daily for 1 week 3
• Target: 60 mg once daily 3
• Some patients may respond to the 30 mg starting dose 3
• No evidence that doses >60 mg confer additional benefit, and higher doses have higher adverse reaction rates 3

Chronic Musculoskeletal Pain (Osteoarthritis, Low Back Pain)

• Initial: 30 mg once daily for 1 week 3
• Target: 60 mg once daily 3
• No evidence that higher doses provide additional benefit 3

Chemotherapy-Induced Peripheral Neuropathy

• Week 1: 30 mg daily 1
• Ongoing: 60 mg daily 1
• Better response seen in cisplatin-treated patients than taxane-treated patients 1

Special Populations

Geriatric Patients (≥65 years)

• Initial: 30 mg once daily for 2 weeks before considering increase 2, 3
• Target: 60 mg once daily 3
• Maximum studied: 120 mg daily 3
• Lower starting doses and slower titration required 1, 2

Pediatric Patients (7-17 years, GAD only)

• Initial: 30 mg once daily for 2 weeks 3
• Target range: 30-60 mg once daily 3
• Maximum studied: 120 mg daily 3
• Increase in 30 mg increments if going beyond 60 mg 3

Hepatic Impairment

• Avoid use in patients with chronic liver disease or cirrhosis 3
• Dose reduction required if used 1

Renal Impairment

• Avoid use in severe renal impairment (CrCl <30 mL/min) 2, 3
• Consider lower starting dose and gradual titration in diabetic patients (frequently complicated by renal disease) 3

Monitoring Requirements

Blood Pressure

• Monitor at each visit, as duloxetine can cause modest hypertension 2, 4

Adverse Effects Assessment

• Assess at each follow-up visit, particularly with higher doses 2, 4
• Watch closely for mood changes in young adults during first few months of treatment 1

Therapeutic Response

• Evaluate using standardized pain or depression scales 1, 4

Common Adverse Effects to Anticipate

• Most common: Nausea (dose-dependent and most common reason for discontinuation) 2, 3
• Other frequent effects: Dry mouth, headache, constipation, dizziness, sedation, hyperhidrosis, decreased libido, somnolence, insomnia, fatigue 2
• Starting at 30 mg for 1 week significantly reduces treatment-emergent nausea 1, 2

Discontinuation Protocol

Taper gradually over at least 2-4 weeks when discontinuing after more than 3 weeks of treatment to minimize withdrawal symptoms (dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, fatigue). 2, 3

For Patients with History of Withdrawal Symptoms

• Use slower taper over 3-4 weeks with smaller decrements 1, 2
• Example: 120 mg → 100 mg → 80 mg → 60 mg 1
• Allow at least one week at each dose level 1

Treatment-Resistant Cases

Inadequate Response at 60 mg Daily for Neuropathic Pain

• Consider adding pregabalin (50-600 mg/day) or gabapentin (900-3600 mg/day) 2, 4

Inadequate Response for Depression

• Consider augmentation with another antidepressant of a different class 2, 4

Critical Drug Interactions

MAOIs

• At least 14 days must elapse between discontinuing an MAOI and starting duloxetine 3
• At least 5 days must elapse after stopping duloxetine before starting an MAOI 3
• Do not start duloxetine in patients receiving linezolid or IV methylene blue due to serotonin syndrome risk 3

CYP450 Interactions

• Avoid concomitant use with potent CYP1A2 inhibitors 3
• Use caution with drugs extensively metabolized by CYP2D6, particularly those with narrow therapeutic index 3