What are the guidelines for prescribing duloxetine (Cymbalta)?

Guidelines for Prescribing Duloxetine (Cymbalta)

Duloxetine should be initiated at 30 mg once daily for 1-2 weeks before increasing to the target therapeutic dose of 60 mg once daily for most indications, with administration as a whole capsule that should not be crushed, chewed, or opened. 1

Indications and Dosing

Major Depressive Disorder (MDD)

• Starting dose: 40-60 mg/day (given as 20 mg twice daily or 30-60 mg once daily)
• Consider starting at 30 mg once daily for 1 week to allow adjustment
• Target dose: 60 mg/day (no evidence that doses >60 mg provide additional benefits)
• Maximum studied dose: 120 mg/day

Generalized Anxiety Disorder (GAD)

• Adults <65 years:

  • Start at 30 mg once daily for 1 week, then increase to 60 mg once daily
  • Target dose: 60 mg/day
  • Maximum dose: 120 mg/day (if needed)

• Geriatric patients (≥65 years):

  • Start at 30 mg once daily for 2 weeks before considering increase
  • Target dose: 60 mg/day
  • Dose increases should be in 30 mg increments

• Pediatric patients (7-17 years):

  • Start at 30 mg once daily for 2 weeks before considering increase
  • Recommended range: 30-60 mg once daily
  • Some patients may benefit from doses above 60 mg daily 2

Pain Conditions

• Diabetic peripheral neuropathic pain: 60 mg once daily 3
• Fibromyalgia: 60 mg once daily 3
• Chronic musculoskeletal pain (osteoarthritis/low back pain): 60 mg once daily 2, 4

Administration Guidelines

• Take orally with or without food
• Swallow capsules whole; do not chew, crush, or open
• If a dose is missed, take it as soon as remembered unless it's almost time for the next dose
• Do not take two doses at the same time 1

Monitoring and Follow-up

Before Initiation

• Screen for:
  • Hepatic impairment (contraindicated in severe hepatic impairment)
  • Uncontrolled narrow-angle glaucoma
  • Use of MAOIs (contraindicated)
  • Renal function
  • Baseline blood pressure and pulse

During Treatment

• Monitor for:
  • Blood pressure and pulse (especially in patients with cardiac disease)
  • Hepatic function (discontinue if jaundice or signs of liver dysfunction develop)
  • Suicidal thoughts/behavior (particularly in patients ≤24 years)
  • Serotonin syndrome (agitation, hallucinations, rapid heartbeat, fever, muscle stiffness)
  • Skin reactions (discontinue at first sign of rash, blisters, or mucosal erosions) 2

Tapering and Discontinuation

• For patients treated >3 weeks: taper over at least 2-4 weeks
• Never abruptly discontinue due to risk of withdrawal symptoms
• Common discontinuation symptoms: dizziness, nausea, headache, paresthesia, irritability 5

Adverse Effects

Common Adverse Effects

• Gastrointestinal: nausea, dry mouth, constipation, diarrhea, vomiting
• Neurological: dizziness, somnolence, headache, insomnia
• Other: diaphoresis, decreased appetite, weight loss 2, 6

Serious Adverse Effects

• Hepatic failure (rare): abdominal pain, hepatomegaly, elevated transaminases
• Severe skin reactions: erythema multiforme, Stevens-Johnson syndrome
• Serotonin syndrome (with concomitant serotonergic agents)
• Increased blood pressure and pulse
• Suicidal ideation (particularly in young adults) 2

Drug Interactions

• Absolute contraindication: MAOIs (wait at least 14 days between stopping MAOIs and starting duloxetine)
• CYP1A2 inhibitors (e.g., fluvoxamine): significantly increase duloxetine exposure by up to 460%
• CYP2D6 substrates: duloxetine may increase levels of drugs metabolized by CYP2D6
• Smoking: decreases duloxetine concentration by approximately 30%
• Anticoagulants: increased risk of bleeding 7

Special Populations

Hepatic Impairment

• Avoid in severe hepatic impairment
• Use caution in mild to moderate impairment

Renal Impairment

• No dose adjustment needed for mild to moderate impairment
• Use caution in severe impairment

Elderly

• Start at lower doses (30 mg once daily)
• Increase dose more gradually
• Monitor more closely for adverse effects 2

Pregnancy and Lactation

• Weigh risks and benefits; consider potential neonatal complications
• Monitor neonates exposed to duloxetine during late pregnancy

Clinical Pearls

• Nausea is the most common side effect but occurs less frequently when starting at 30 mg/day and titrating after one week 8
• Pain relief may occur within one week at the 60 mg/day dose
• Duloxetine is particularly useful when pain co-occurs with depression or anxiety
• Avoid concomitant use with potent CYP1A2 inhibitors 7
• Consider duloxetine as an alternative to opioids for chronic pain conditions, as opioids are not recommended for conditions like osteoarthritis 2