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

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

Duloxetine is indicated for diabetic peripheral neuropathy, osteoarthritis pain, fibromyalgia, major depressive disorder, generalized anxiety disorder, and should be initiated at 30 mg daily and increased to 60 mg daily for most conditions. 1, 2

Indications

FDA-Approved Indications:

• Diabetic peripheral neuropathy (DPN): First-line treatment for neuropathic pain 1
• Osteoarthritis pain: Second-line or combination treatment for knee and hip OA 1
• Fibromyalgia: Effective for pain reduction 3, 4
• Major depressive disorder (MDD): Effective for both emotional and physical symptoms 5
• Generalized anxiety disorder (GAD): First-line treatment option 6

Dosing Guidelines

Initial Dosing and Titration:

• Starting dose: 30 mg once daily for 1 week 1, 7, 2
• Target dose: 60 mg once daily (most effective dose for most conditions) 1, 7
• Maximum dose: 60 mg twice daily (120 mg/day) 7

Administration:

• Can be taken with or without food 2
• Swallow capsules whole; do not chew, crush, or open 2
• For missed doses: Take as soon as remembered unless close to next scheduled dose 2

Special Populations:

• Renal insufficiency: Dosage adjustments may be required 7
• Hepatic impairment: Contraindicated in severe hepatic impairment 7, 2
• Elderly: Effective in patients ≥65 years with GAD; monitor closely 6

Discontinuation:

• Never abruptly discontinue: Taper over 2-4 weeks to prevent discontinuation syndrome 1, 7, 2
• For patients on treatment >3 weeks, taper by reducing dose by 25-30% every 2 weeks 7

Side Effects and Safety

Common Side Effects (10-20% of patients):

• Nausea (most common, especially during initiation) 2, 8
• Dry mouth, dizziness, headache, constipation 7, 2
• Somnolence, fatigue, insomnia 7, 2
• Decreased appetite, weight loss 2
• Diaphoresis (excessive sweating) 7, 8

Serious Side Effects (rare but important):

• Serotonin syndrome: Agitation, hallucinations, rapid heartbeat, fever, muscle rigidity 2
• Abnormal bleeding: Especially with concomitant NSAIDs, aspirin, or warfarin 2
• Blood pressure changes: Can increase or decrease blood pressure; monitor regularly 2
• Severe skin reactions: May require discontinuation 2
• Hepatotoxicity: Monitor for right upper abdominal pain, dark urine, jaundice 2
• Suicidal thinking: Particularly in young adults and adolescents 7, 2

Absolute Contraindications:

• Concomitant use of MAOIs 7, 2
• Uncontrolled narrow-angle glaucoma 7
• Severe hepatic impairment 7, 2

Drug Interactions

Major Interactions:

• MAOIs: Contraindicated; risk of serotonin syndrome 7, 2
• CYP1A2 inhibitors: Avoid concomitant use (e.g., fluvoxamine, ciprofloxacin) 2, 8
• CYP2D6 substrates: Use with caution, especially those with narrow therapeutic index 2
• Anticoagulants/antiplatelets: Increased bleeding risk 2
• Other serotonergic drugs: Increased risk of serotonin syndrome 2
• Alcohol: Avoid heavy alcohol use; risk of severe liver injury 2

Practical Considerations

Monitoring:

• Blood pressure: Before starting and throughout treatment 2
• Hepatic function: Monitor for signs of liver damage 2
• Weight and height: Particularly in pediatric patients 2
• Mental status: Watch for worsening depression, suicidal ideation 7, 2

Efficacy Timeline:

• Pain relief may begin within 1 week at 60 mg daily dose 8
• Full therapeutic effect may take 2-4 weeks 6, 5

Comparative Efficacy:

• For neuropathic pain: Similar efficacy to pregabalin and gabapentin 1, 3
• For depression: Similar global benefit-risk profile to venlafaxine XR; comparable to paroxetine and escitalopram 5

Clinical Pearls

• Initiating at 30 mg daily for one week before increasing to 60 mg daily significantly reduces nausea and improves tolerability 8
• Duloxetine is effective for both the emotional symptoms of depression and the physical pain symptoms 5
• For osteoarthritis, duloxetine is recommended as a second-line or combination treatment after topical agents, acetaminophen, and NSAIDs 1
• The NNT for 50% pain reduction in diabetic neuropathy is 5-6 patients, indicating good efficacy 3, 4
• Discontinuation symptoms are common and include dizziness, nausea, headache, and irritability; always taper gradually 2