Duloxetine (Cymbalta): Indications, Dosing, and Side Effects
Duloxetine is indicated for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, and chronic pain conditions, with a standard therapeutic dose of 60mg once daily for most conditions. 1, 2
Indications
Duloxetine is FDA-approved for:
- Major Depressive Disorder (MDD)
- Generalized Anxiety Disorder (GAD)
- Diabetic Peripheral Neuropathic Pain
- Fibromyalgia
- Chronic musculoskeletal pain
Dosing Guidelines
Standard Dosing
- Initial dose: 30mg once daily for 1 week, then increase to 60mg once daily
- Starting at 30mg reduces initial side effects, particularly nausea 3
- Maintenance dose: 60mg once daily (most effective dose for most indications)
- Maximum dose: 60mg twice daily (120mg/day) 1
Special Populations
- Renal insufficiency: Dosage adjustment required 1
- Severe hepatic impairment: Contraindicated 1, 2
- Elderly: Standard dosing applies, but monitor closely
Administration
- May be taken with or without food
- Swallow capsules whole; do not chew, crush, open, or sprinkle on food 2
- If a dose is missed, take as soon as remembered unless it's almost time for the next dose 2
Efficacy
- Diabetic neuropathy: Effective at 60mg daily with NNT of 5 for 50% pain reduction 4, 5
- Fibromyalgia: Effective at 60-120mg daily with NNT of 8 for 50% pain reduction 4, 5
- Depression with painful symptoms: Effective with NNT of 8 4
- GAD: Significantly improves anxiety symptoms and functional impairment 6
Side Effects
Common Side Effects (>5%)
- Gastrointestinal: Nausea, dry mouth, constipation, diarrhea, vomiting, decreased appetite 1, 2
- Neurological: Dizziness, headache, somnolence, insomnia, fatigue, tremor 1, 2
- Other: Diaphoresis (excessive sweating), weight loss 1, 2
Serious Side Effects
- Liver damage: Monitor for right upper abdominal pain, dark urine, jaundice 2
- Blood pressure changes: Can increase or decrease blood pressure; monitor regularly 2
- Serotonin syndrome: Agitation, hallucinations, rapid heartbeat, fever, muscle rigidity 2
- Abnormal bleeding: Especially with concomitant NSAIDs, aspirin, or warfarin 2
- Severe skin reactions: Rash, blisters, peeling skin 2
- Suicidal thinking: Particularly in children, adolescents, and young adults 1, 2
- Seizures: Rare but possible 2
- Hyponatremia: Low sodium levels, more common in elderly 2
Contraindications
Absolute contraindications:
Relative contraindications:
Drug Interactions
Significant Interactions
- MAOIs: Contraindicated due to risk of serotonin syndrome 1, 2
- CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin): Avoid concomitant use 2, 3
- CYP2D6 substrates (e.g., tricyclics, thioridazine): Use with caution 2
- Serotonergic drugs (e.g., triptans, SSRIs, tramadol): Increased risk of serotonin syndrome 2
- NSAIDs/anticoagulants: Increased bleeding risk 2
- CNS depressants: Additive effects 2
Discontinuation
- Never stop abruptly: Taper gradually to avoid discontinuation syndrome 1, 2
- Tapering protocol: Reduce dose by 25-30% every 2 weeks 1
- Discontinuation symptoms: Dizziness, headache, nausea, irritability, sensory disturbances 1, 2
Monitoring Recommendations
- Blood pressure: Before starting and periodically throughout treatment 2
- Hepatic function: Monitor for signs of liver damage 2
- Mental status: Watch for behavioral activation, suicidal ideation 1, 2
- Weight and appetite: Regular monitoring, especially in pediatric patients 2
- Sodium levels: Consider monitoring in elderly patients 2
Clinical Pearls
- Nausea is the most common side effect leading to discontinuation; starting at 30mg and titrating up reduces this risk 3
- Pain relief in neuropathic conditions can begin within one week at therapeutic doses 3
- Duloxetine is effective for both emotional symptoms of depression and associated physical pain 7
- Consider for patients with comorbid depression/anxiety and chronic pain conditions 4, 5
- Monitor closely during the first 1-2 weeks of treatment when side effects are most common 1