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

Standard Dosing by Indication

Generalized Anxiety Disorder (Adults <65 years)

• Initial: 30 mg once daily for 1 week to allow adjustment 2
• Target: 60 mg once daily 2
• Maximum: 120 mg once daily (though no evidence that doses >60 mg provide additional benefit) 2
• Titration: If increasing beyond 60 mg, use 30 mg increments 2

Generalized Anxiety Disorder (Geriatric Patients ≥65 years)

• Initial: 30 mg once daily for 2 weeks 2
• Target: 60 mg once daily 2
• Maximum: 120 mg once daily 2
• Lower starting doses and slower titration are required in this population 1

Diabetic Peripheral Neuropathic Pain

• Dose: 60 mg once daily 2, 3
• Key point: No evidence that doses >60 mg confer additional benefit, and higher doses are clearly less well tolerated 2
• For tolerability concerns, consider starting at 30 mg daily 2

Fibromyalgia

• Initial: 30 mg once daily for 1 week 2
• Target: 60 mg once daily 2
• Evidence: Some patients respond to 30 mg, but no benefit from doses >60 mg 2, 4

Chronic Musculoskeletal Pain (Osteoarthritis, Low Back Pain)

• Initial: 30 mg once daily for 1 week 2
• Target: 60 mg once daily 2, 3
• Must be taken daily for effectiveness 1

Chemotherapy-Induced Peripheral Neuropathy

• Week 1: 30 mg once daily 1
• Week 2 onward: 60 mg once daily 1
• Better response in cisplatin-treated patients than taxane-treated patients 1

Special Populations

Hepatic Impairment

• Avoid use in patients with chronic liver disease or cirrhosis 2
• Dose reduction required if used 1

Renal Impairment

• Avoid use in patients with severe renal impairment (CrCl <30 mL/min) 1, 2
• Consider lower starting dose and gradual titration in diabetic patients with renal disease 2

Monitoring Requirements

Essential Monitoring

• Blood pressure at each visit (duloxetine can cause modest hypertension) 1, 5, 6
• Adverse effects assessment at each follow-up, particularly with higher doses 1, 5, 6
• Therapeutic response using standardized pain or depression scales 1, 5, 6
• Mood changes in young adults during first few months of treatment 1

Common Adverse Effects to Monitor

• Nausea (most common, dose-dependent) 1, 6
• Sedation, dizziness 6
• Hyperhidrosis 6
• Dry mouth, headache, constipation 7
• Decreased libido, somnolence or insomnia 7

Discontinuation Protocol

Taper gradually over at least 2-4 weeks when discontinuing after more than 3 weeks of treatment. 1, 2

Standard Taper

• Reduce dose gradually rather than stopping abruptly 2
• Use at least 1 week intervals at each dose level 1

For Patients with History of Withdrawal Symptoms

• Slower taper over 3-4 weeks with smaller decrements 1
• Example: 120 mg → 100 mg → 80 mg → 60 mg → discontinue 1

Expected Discontinuation Symptoms

• Dizziness, headache, nausea, diarrhea 2
• Paresthesia, irritability, vomiting 2
• Insomnia, anxiety, hyperhidrosis, fatigue 2

Drug Interactions

Contraindications

• MAOIs: Allow 14 days between stopping MAOI and starting duloxetine 2
• Duloxetine to MAOI: Allow 5 days after stopping duloxetine before starting MAOI 2
• Linezolid or IV methylene blue: Do not start duloxetine in patients receiving these agents 2

Use with Caution

• Avoid concomitant use with potent CYP1A2 inhibitors 8
• Use caution with drugs extensively metabolized by CYP2D6, particularly those with narrow therapeutic index 8

Treatment-Resistant Cases

If Inadequate Response at 60 mg Daily

• For neuropathic pain: Consider adding pregabalin (50-600 mg/day) or gabapentin (900-3600 mg/day) 6
• For depression: Consider augmentation with another antidepressant of different class 6
• Refer to pain specialist or psychiatrist for alternative options 6