Duloxetine Dosing for Generalized Anxiety Disorder
For adults under 65 years with GAD, start duloxetine at 60 mg once daily, or begin at 30 mg once daily for 1 week to improve tolerability before increasing to the target dose of 60 mg once daily. 1
Standard Adult Dosing (Age <65 years)
- Initial dose: 60 mg once daily is the recommended starting dose for most adults with GAD 1
- Alternative initiation: 30 mg once daily for 1 week, then increase to 60 mg once daily for patients who need to adjust to the medication before reaching therapeutic dose 1, 2
- Maximum dose: 120 mg once daily, though doses above 60 mg/day have not demonstrated additional benefit in clinical trials 1, 3
- Dose escalation: If increasing beyond 60 mg once daily, titrate in 30 mg increments 1
Geriatric Dosing (Age ≥65 years)
- Initial dose: 30 mg once daily for 2 weeks before considering increase to target dose 1
- Target dose: 60 mg once daily after the initial 2-week period 1
- Maximum dose: 120 mg once daily if needed, increased in 30 mg increments 1
Pediatric Dosing (Ages 7-17 years)
- Initial dose: 30 mg once daily for 2 weeks 1
- Target dose range: 30-60 mg once daily 1
- Dose escalation: Increase in 30 mg increments if doses above 60 mg are needed 1
- Maximum studied dose: 120 mg once daily 1
Administration Guidelines
- Timing: Take once daily with or without food 1
- Formulation: Swallow capsules whole; do not chew, crush, or open capsules as this affects the enteric coating 1
- Missed dose: Take as soon as remembered unless close to next scheduled dose; never double dose 1
Clinical Efficacy Evidence
- Onset of action: Symptom improvement begins within the first few weeks of treatment and continues throughout therapy 3, 4
- Response rates: Duloxetine 60-120 mg once daily demonstrates significant improvement on Hamilton Anxiety Rating Scale (HAM-A) scores compared to placebo in multiple randomized controlled trials 2, 4
- Relapse prevention: Duloxetine effectively prevents or delays relapse in responders during continuation treatment 2
- Pain comorbidity: In GAD patients with clinically significant pain symptoms (VAS pain score ≥30), duloxetine reduces both anxiety and pain severity 5
Special Populations and Dose Adjustments
- Hepatic impairment: Avoid use in patients with chronic liver disease or cirrhosis 1
- Severe renal impairment: Avoid use in patients with GFR <30 mL/minute 1
- Diabetic patients: Consider lower starting dose and gradual titration since diabetes frequently complicates renal function 1
Common Adverse Effects
- Most frequent: Nausea (most common), dry mouth, headache, constipation, dizziness, fatigue, somnolence 1, 2, 4
- Severity: Most adverse events are mild to moderate and transient 2, 3
- Discontinuation rates: Nausea is the primary reason for treatment discontinuation 2
Discontinuation Protocol
- Taper required: Gradually reduce dose when discontinuing to prevent withdrawal symptoms, especially after treatment longer than 3 weeks 6
- Withdrawal symptoms: Dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, fatigue 1
Monitoring Requirements
- Blood pressure and pulse: Monitor regularly during treatment as duloxetine can increase both parameters 7
- Hepatic function: Monitor for signs of hepatic dysfunction given rare risk of hepatic failure 6
- Suicidality: Monitor for suicidal thinking and behavior, particularly in younger patients 6
Key Clinical Pearls
- No additional benefit above 60 mg: While 120 mg daily has been studied and shown effective, there is no evidence that doses greater than 60 mg/day confer additional benefit, and higher doses are associated with increased adverse events 1, 2, 3
- Comparative efficacy: Pooled data show duloxetine produces HAM-A score improvements of similar magnitude to venlafaxine extended-release 2
- Chinese population data: Duloxetine 60-120 mg once daily is effective and well-tolerated in Chinese patients with GAD 4