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

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

Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, major depressive disorder, and chronic musculoskeletal pain, with dosing ranging from 30-120 mg daily depending on indication.

Indications

FDA-Approved Indications:

• Generalized Anxiety Disorder (GAD)

  • Only SNRI with FDA indication for GAD in children and adolescents 7 years and older 1
  • Effective for anxiety symptoms with significant improvement over placebo 2

• Diabetic Peripheral Neuropathic Pain (DPNP)

  • First-line treatment for neuropathic pain 1
  • Recommended initial pharmacologic treatment along with pregabalin and gabapentin 1
  • Effective for pain reduction with number needed to treat (NNT) of 5 for 50% pain reduction 3

• Fibromyalgia

  • Effective for pain reduction with NNT of 8 for 50% pain reduction 3
  • Efficacy demonstrated in both short-term (12 weeks) and longer-term (28 weeks) treatment 3

• Major Depressive Disorder (MDD)

  • Effective for both emotional symptoms and painful physical symptoms associated with depression 4
  • Improvements typically apparent after 1-2 weeks at 60 mg daily dosage 4

Dosing Guidelines

General Dosing:

• Starting dose: 30-60 mg once daily
• Effective dose range: 60-120 mg daily
• Maximum recommended dose: 120 mg daily

Indication-Specific Dosing:

1. Diabetic Peripheral Neuropathy:

   • Recommended dose: 60 mg once daily 1
   • Effective dose range: 60-120 mg daily 3

2. Generalized Anxiety Disorder:

   • Recommended dose: 60 mg once daily 2
   • Effective dose range: 60-120 mg once daily 2

3. Fibromyalgia:

   • Recommended dose: 60 mg once daily 1
   • Effective dose range: 60-120 mg daily 3

Special Populations:

• Elderly: Start at lower doses and titrate slowly 5
• Renal impairment: Dose adjustment required based on creatinine clearance 5
• Hepatic impairment: Avoid in severe liver disease; use caution in mild to moderate impairment 6

Administration:

• May be taken with or without food 6
• Swallow capsules whole; do not chew, crush, or open 6
• For missed doses: Take as soon as remembered unless close to next dose 6

Side Effects

Common Side Effects:

• Nausea (most common) 7
• Dry mouth
• Constipation
• Dizziness
• Fatigue
• Somnolence
• Decreased appetite
• Increased sweating 6

Serious Adverse Effects:

1. Hepatotoxicity:

   • Hepatic failure presenting as abdominal pain, hepatomegaly, and elevated transaminases
   • Cholestatic jaundice
   • Discontinue if jaundice or evidence of liver dysfunction occurs 1

2. Cardiovascular Effects:

   • Sustained hypertension
   • Increased blood pressure
   • Increased pulse 1

3. Dermatological Reactions:

   • Severe skin reactions including erythema multiforme and Stevens-Johnson syndrome
   • Discontinue at first appearance of blisters, peeling rash, or mucosal erosions 1

4. Neuropsychiatric Effects:

   • Suicidal thinking and behavior (through age 24 years)
   • Behavioral activation/agitation
   • Hypomania/mania
   • Seizures 1, 6

5. Other Serious Effects:

   • Serotonin syndrome (risk increases with concomitant serotonergic drugs)
   • Abnormal bleeding (especially with anticoagulants, NSAIDs, or aspirin)
   • Sexual dysfunction 1, 6

Drug Interactions

Significant Interactions:

• MAOIs: Contraindicated due to risk of serotonin syndrome 6
• CYP1A2 inhibitors: Avoid concomitant use 6
• CYP2D6 substrates: Use caution, especially with narrow therapeutic index drugs 6
• Anticoagulants/Antiplatelets: Increased bleeding risk 6
• Other serotonergic drugs: Increased risk of serotonin syndrome 6

Monitoring and Follow-up

• Monitor blood pressure and pulse regularly
• Monitor for signs of liver dysfunction
• Monitor for emergence of suicidal thoughts, especially in younger patients
• Assess for clinical improvement in target symptoms
• Monitor for discontinuation symptoms if stopping treatment

Important Considerations

• Discontinuation: Taper gradually to minimize discontinuation symptoms (anxiety, irritability, dizziness, electric shock-like sensations, headache, nausea) 6
• Pregnancy: Use caution; may cause complications when used late in pregnancy 6
• Pediatric use: Monitor height and weight in children and adolescents 6
• Overdose: No specific antidote; supportive care is primary management 6

Clinical Pearls

• Initiating at 30 mg daily for one week before increasing to 60 mg daily may reduce initial nausea 7
• Pain relief may occur within one week at therapeutic doses 7
• Duloxetine has a generally favorable side effect profile compared to other antidepressants 4
• Consider as first-line therapy for patients with both depression and painful symptoms 4