Duloxetine (Cymbalta): Indications, Dosing, and Side Effects
Duloxetine is FDA-approved for treating diabetic peripheral neuropathy, fibromyalgia, major depressive disorder, generalized anxiety disorder, chronic musculoskeletal pain, and stress urinary incontinence, with a standard dosing range of 30-120 mg daily depending on indication. 1
Indications
Duloxetine is indicated for:
- Diabetic peripheral neuropathy: First-line treatment, especially in patients with history of GI bleeding (safer than NSAIDs) 2
- Fibromyalgia: Effective for pain management 3
- Major depressive disorder
- Generalized anxiety disorder
- Chronic musculoskeletal pain (including sciatica)
- Stress urinary incontinence
Dosing Guidelines
Standard Dosing by Indication:
| Indication | Starting Dose | Target Dose |
|---|---|---|
| Neuropathic Pain | 30 mg daily | 60-120 mg/day |
| Depression/Anxiety | 30-40 mg daily | 60 mg/day |
| Fibromyalgia | 30 mg daily | 60 mg/day |
| Chronic Pain | 30 mg daily | 60 mg/day |
Administration Guidelines:
- Swallow capsules whole; do not chew, crush, or open 1
- May be taken with or without food 1
- For missed doses: Take as soon as remembered unless close to next dose 1
- When discontinuing: Taper gradually to avoid withdrawal symptoms 1
- Start at 30 mg daily for one week before increasing to 60 mg daily to minimize initial side effects, particularly nausea 4
Side Effects
Common Side Effects:
- Gastrointestinal: Nausea (most common, dose-dependent - 37.8% at 60 mg/day vs 16.4% at 40 mg/day), dry mouth, constipation, decreased appetite 1, 5
- Neurological: Dizziness, somnolence, fatigue, headache, insomnia 1
- Other: Increased sweating, sexual dysfunction 1
Serious Side Effects:
- Liver damage: Monitor for right upper abdominal pain, dark urine, jaundice 1
- Serotonin syndrome: Agitation, hallucinations, rapid heartbeat, fever, muscle rigidity 1
- Abnormal bleeding: Especially with concomitant use of NSAIDs, aspirin, or anticoagulants 1
- Blood pressure changes and falls: Monitor blood pressure regularly, especially in elderly patients 1
- Severe skin reactions: Including blisters, peeling rash, hives 1
- Discontinuation syndrome: Anxiety, irritability, headache, dizziness, electric shock-like sensations 1
Special Populations and Precautions
Contraindications:
- Concomitant use with MAOIs
- Uncontrolled narrow-angle glaucoma
- Severe liver disease 1
Pregnancy and Breastfeeding:
- May cause harm to developing fetus; use with caution during pregnancy
- Passes into breast milk; discuss risks with healthcare provider 1
Pediatric Patients:
- Monitor for weight loss and growth changes
- Decreased appetite and weight loss more common than in adults 1
Elderly Patients:
- More susceptible to side effects; may require lower doses
- Higher risk of falls and blood pressure changes 1
Drug Interactions:
- MAOIs: Contraindicated due to risk of serotonin syndrome
- Triptans, other serotonergic drugs: Increased risk of serotonin syndrome
- NSAIDs, anticoagulants: Increased bleeding risk
- CYP1A2 inhibitors: May increase duloxetine levels
- CNS depressants: Additive effects with alcohol and other sedatives 1
Monitoring Recommendations
- Initial phase: Monitor for side effects, especially nausea, dizziness, and blood pressure changes
- Long-term: Regular assessment of pain control, function, and adverse effects
- Discontinuation: Gradual tapering required to minimize withdrawal symptoms 2, 1
Clinical Pearls
- Duloxetine offers advantages for patients with GI bleeding history compared to NSAIDs 2
- Initial side effects (particularly nausea) often improve after the first week of treatment 4, 6
- Therapeutic effects for pain may be seen within one week at 60 mg daily dosing 4
- Higher doses (90-120 mg) provide minimal additional benefit for most patients but increase side effects 5, 6
- Avoid heavy alcohol use due to risk of severe liver injury 1