Cymbalta (Duloxetine) Titration
Start duloxetine at 30 mg once daily for 1 week, then increase to the therapeutic dose of 60 mg once daily for most indications. This approach significantly reduces treatment-emergent nausea (the most common adverse effect) while producing only a transient delay in therapeutic effect compared to starting at 60 mg daily 1, 2, 3.
Standard Titration Schedule
The recommended titration is straightforward:
The FDA label confirms this approach across multiple indications including major depressive disorder, generalized anxiety disorder, fibromyalgia, and chronic musculoskeletal pain 3. This initial lower dose allows patients to adjust to the medication before reaching therapeutic levels 1.
Administration Details
- Take with or without meals—swallowing capsules whole without chewing, crushing, or opening 3
- Taking duloxetine with food can further improve tolerability, particularly if starting at 60 mg, though the 30 mg starting dose minimizes this concern 4
- Administer once daily at any consistent time 3
Indication-Specific Considerations
For diabetic peripheral neuropathic pain: The standard 60 mg once daily dose is recommended, with no evidence that higher doses provide additional benefit 3. Consider starting at a lower dose in patients with renal impairment, as diabetes frequently complicates renal function 3.
For chemotherapy-induced peripheral neuropathy: Use 30 mg daily for 1 week, then 60 mg daily, with better response demonstrated in cisplatin-treated patients than taxane-treated patients 1, 2.
For geriatric patients (≥65 years): Start at 30 mg once daily for 2 weeks before increasing to 60 mg daily 3. Lower starting doses and slower titration are required in this population 1, 2.
For pediatric patients (7-17 years) with GAD: Initiate at 30 mg once daily for 2 weeks before considering increase to 60 mg once daily, with a recommended range of 30-60 mg daily 3.
Dose Escalation Beyond 60 mg
While 120 mg/day has been studied and shown effective, there is no evidence that doses greater than 60 mg/day confer additional benefits 3. Higher doses are associated with higher rates of adverse reactions without improved efficacy 1, 3.
If escalation is attempted:
- Increase in increments of 30 mg once daily 3
- Maximum studied dose is 120 mg daily 3
- Monitor closely for adverse effects, particularly at higher doses 1, 5
Monitoring Requirements
Essential monitoring includes:
- Blood pressure at each visit, as duloxetine can cause modest hypertension 5, 2
- Assessment for adverse effects at each follow-up, particularly nausea, sedation, dizziness, hyperhidrosis, dry mouth, and constipation 5, 2
- Therapeutic response using standardized pain or depression scales 1, 5, 2
- Close monitoring for mood changes in young adults during the first few months, particularly suicidal ideation 1
Special Population Adjustments
Hepatic impairment: Dose reduction is required if duloxetine is used 1, 2
Renal impairment: Avoid use in patients with creatinine clearance <30 mL/min 1, 2
Discontinuation Protocol
When stopping duloxetine after more than 3 weeks of treatment, taper gradually over at least 2-4 weeks 1, 2. For patients with a history of withdrawal symptoms, use a slower taper over 3-4 weeks with smaller dose decrements (e.g., 120 mg → 100 mg → 80 mg → 60 mg → 30 mg) 1. Use small increments at intervals that allow adequate observation, usually at least a week at each dose level 1.
Common Pitfalls to Avoid
- Starting at 60 mg without titration: This increases nausea and early discontinuation rates 1, 4
- Exceeding 60 mg daily without clear rationale: Higher doses increase adverse effects without proven additional benefit 3
- Abrupt discontinuation: This causes withdrawal symptoms including nausea and dizziness 6
- Use in severe renal impairment: Contraindicated when CrCl <30 mL/min 2