What are the indications, dosing, and potential side effects of duloxetine (Cymbalta)?

Duloxetine (Cymbalta): Indications, Dosing, and Side Effects

Duloxetine is FDA-approved for treating diabetic peripheral neuropathy, generalized anxiety disorder, fibromyalgia, and major depressive disorder, with dosing typically starting at 30 mg daily and increasing to 60 mg daily for most conditions. 1

Indications

Duloxetine is indicated for several conditions:

1. Neuropathic Pain

   • First-line treatment for diabetic peripheral neuropathy 2, 3
   • Effective for chemotherapy-induced peripheral neuropathy 2

2. Psychiatric Disorders

   • Major depressive disorder 1, 4
   • Generalized anxiety disorder (FDA-approved for children and adolescents 7 years and older) 2

3. Chronic Pain Conditions

   • Fibromyalgia 5, 3
   • Chronic musculoskeletal pain 5

Dosing Guidelines

Initial Dosing and Titration

• Starting dose: 30 mg daily for 1 week 5, 6
• Target dose: 60 mg daily (standard effective dose for most conditions) 2, 5
• Maximum dose: 120 mg daily (for certain conditions) 1, 7

Condition-Specific Dosing

1. Neuropathic Pain:

   • Start: 30 mg daily
   • Target: 60-120 mg/day 5
   • Note: 60 mg daily is more consistently effective than lower doses 4

2. Anxiety Disorders:

   • Children (≥7 years): Start at lower doses with careful titration 2
   • Adults: 30 mg daily initially, then 60 mg daily 2

3. Depression:

   • 60 mg once daily or 30 mg twice daily 4

Administration

• May be taken with or without food 1
• Capsules should be swallowed whole; do not chew, crush, or open 1
• For missed doses: Take as soon as remembered unless it's almost time for the next dose 1

Side Effects

Common Side Effects (>10%)

• Nausea (most common, especially at initiation) 1, 6, 4
• Dry mouth 1, 4
• Headache 1, 4
• Dizziness 1, 4
• Fatigue/somnolence 1
• Constipation 1
• Decreased appetite 1, 7
• Insomnia 1, 4
• Increased sweating 1

Serious Side Effects (Rare)

• Liver damage: Monitor for right upper abdominal pain, dark urine, yellow skin/eyes 1
• Serotonin syndrome: Agitation, hallucinations, fever, muscle rigidity, rapid heartbeat 1
• Blood pressure changes: Can increase blood pressure or cause orthostatic hypotension 1
• Abnormal bleeding: Especially when combined with NSAIDs, aspirin, or warfarin 1
• Severe skin reactions: Blisters, peeling rash, sores in mouth 1
• Seizures 1
• Hyponatremia: Headache, weakness, confusion (higher risk in elderly) 1

Special Populations

• Elderly: More susceptible to side effects; may require lower doses 5
• Hepatic impairment: Contraindicated in liver disease 5
• Renal impairment: May require dose adjustments 5
• Pediatric patients: Monitor height and weight; may cause weight loss 1
• Pregnancy: Use with caution; may harm the baby 1
• Breastfeeding: Passes into breast milk 1

Drug Interactions

Significant Interactions

• MAOIs: Contraindicated; risk of serotonin syndrome 1
• CYP1A2 inhibitors: Avoid concomitant use 1, 6
• Serotonergic drugs: Triptans, SSRIs, other SNRIs, tramadol (increased risk of serotonin syndrome) 1
• NSAIDs/Anticoagulants: Increased bleeding risk 1
• Alcohol: Avoid heavy alcohol use; risk of severe liver injury 1

Monitoring Recommendations

• Blood pressure and heart rate: Before starting and throughout treatment 1
• Liver function: Monitor for signs of liver damage 1
• Mental status: Watch for worsening depression, suicidal thoughts (especially in young adults) 1
• Weight: Regular monitoring, especially in pediatric patients 1

Important Precautions

• Discontinuation: Never stop abruptly; taper gradually to avoid withdrawal symptoms (anxiety, irritability, dizziness, electric shock-like sensations) 1
• Driving/operating machinery: May impair judgment, thinking, or motor skills 1
• Suicide risk: Increased risk in children, adolescents, and young adults; monitor closely 1
• Bleeding risk: Use caution in patients on anticoagulants or with bleeding disorders 1

Duloxetine is generally well-tolerated when properly dosed and monitored, with most side effects occurring during initial treatment and subsiding over time 7.