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

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

Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor (SSNRI) that is FDA-approved for treating painful diabetic peripheral neuropathy, fibromyalgia, major depressive disorder, and generalized anxiety disorder, with 60 mg once daily being the most effective standard dose for most conditions. 1, 2

Indications

FDA-Approved Indications:

• Painful Diabetic Peripheral Neuropathy (DPN) 1
• Fibromyalgia 1
• Major Depressive Disorder (MDD) 2
• Generalized Anxiety Disorder (GAD) 2

Off-Label Uses:

• Chronic pain conditions 1
• Neuropathic pain of various origins 1
• Chronic gastrointestinal pain in disorders of gut-brain interaction 1

Dosing Guidelines

Standard Dosing:

• Initial dose: 30 mg once daily for 1 week 1
• Target dose: 60 mg once daily 1, 2
• Maximum dose: 60 mg twice daily (120 mg/day) 1, 2
• Duration of adequate trial: 4 weeks 1

Special Populations:

• Elderly patients: Consider lower starting doses and slower titration 1
• Hepatic impairment: Use with caution; contraindicated in severe hepatic impairment 2
• Renal impairment: Dosage reduction may be required 2

Side Effects

Common Side Effects (>10%):

• Nausea (most common, especially at initiation) 1, 2, 3
• Dry mouth 2
• Somnolence/sedation 2
• Fatigue 2
• Constipation 1, 2
• Decreased appetite 2
• Dizziness 2
• Hyperhidrosis (increased sweating) 2

Serious Side Effects (rare but important):

• Serotonin syndrome 2
• Abnormal bleeding risk (especially with NSAIDs, aspirin, or warfarin) 2
• Severe skin reactions 2
• Hypertension or hypotension 2
• Hepatotoxicity (rare) 2
• Seizures 2
• Hyponatremia 2

Discontinuation Symptoms:

• Abrupt discontinuation may lead to withdrawal symptoms including: 2
  • Dizziness
  • Headache
  • Nausea
  • Anxiety
  • Irritability
  • "Electric shock-like" sensations
  • Insomnia

Efficacy

Neuropathic Pain:

• Diabetic Peripheral Neuropathy: Moderate to strong evidence of efficacy with NNT of 5-6 for ≥50% pain reduction 1, 4
• More effective for platinum-based chemotherapy-induced neuropathy than taxane-induced neuropathy 1

Depression:

• Effective for major depressive disorder, with improvement typically seen within 1-2 weeks at 60 mg/day 5, 6
• Also effective for painful physical symptoms associated with depression 2, 5

Important Precautions

Drug Interactions:

• Avoid with:
  • MAOIs (risk of serotonin syndrome) 2
  • CYP1A2 inhibitors 2, 3
• Use with caution with:
  • NSAIDs (increased bleeding risk) 2
  • Warfarin (increased bleeding risk) 2
  • Other serotonergic drugs 2

Pregnancy and Breastfeeding:

• Passes into breast milk; discuss risks and benefits 2
• Potential risks to fetus; inform healthcare provider if pregnant or planning pregnancy 2

Alcohol:

• Avoid heavy alcohol use while taking duloxetine (risk of liver injury) 2

Practical Tips for Prescribing

• To minimize nausea: Start with 30 mg once daily for 1 week before increasing to 60 mg 1, 3
• Take with or without food 2
• Swallow capsules whole - do not chew, crush, or open 2
• Taper gradually when discontinuing to avoid withdrawal symptoms 2
• Monitor blood pressure before and during treatment 2
• For elderly patients, use lower starting doses and slower titration 1

Comparison to Other Medications

• More consistent evidence for neuropathic pain than gabapentin 1
• Similar efficacy to venlafaxine for neuropathic pain, but duloxetine has simpler dosing 1
• Fewer anticholinergic side effects than tricyclic antidepressants 1
• Unlike opioids, duloxetine has low addiction potential 1

Duloxetine represents an important first-line option for neuropathic pain conditions and offers the additional benefit of treating comorbid depression and anxiety when present.