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Resources › Psychotropics A-Z › Duloxetine | Cymbalta | Cymbalta
Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)

Duloxetine | Cymbalta

Clinical Overview

Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI) indicated for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain. Its dual mechanism makes it particularly effective for depression with pain symptoms.

Primary Clinical Applications

Duloxetine is effective for major depressive disorder, generalized anxiety disorder, and various chronic pain conditions. Its unique dual reuptake inhibition provides benefits for both mood and pain symptoms, making it valuable for patients with comorbid depression and chronic pain conditions.

Mechanism and Clinical Benefits

Duloxetine inhibits both serotonin and norepinephrine reuptake with relatively balanced potency. This dual mechanism contributes to its efficacy in treating both emotional and physical symptoms of depression, as well as providing analgesic effects for neuropathic and musculoskeletal pain.

Clinical Considerations

The medication is available as delayed-release capsules that should be swallowed whole. Duloxetine requires gradual dose titration and tapering to minimize side effects and discontinuation symptoms. It may take 4-6 weeks to achieve full therapeutic benefits for depression and anxiety.

Prescribing Information

Dosing & Administration

Major Depressive Disorder – Adults:

  • Initial: 40 mg daily (20 mg twice daily) or 60 mg once daily
  • Target: 60 mg once daily
  • Range: 40-120 mg daily
  • Maximum: 120 mg daily

Generalized Anxiety Disorder:

  • Initial: 60 mg once daily
  • Range: 60-120 mg daily
  • Maximum: 120 mg daily

Diabetic Peripheral Neuropathy:

  • Recommended dose: 60 mg once daily
  • Maximum: 60 mg daily (higher doses not more effective)

Fibromyalgia:

  • Initial: 30 mg once daily for 1 week
  • Target: 60 mg once daily
  • Maximum: 60 mg daily

Administration:

  • Swallow capsules whole, do not open or chew
  • Take with or without food
  • Same time each day

Indications

  • Major depressive disorder (adults)
  • Generalized anxiety disorder (adults)
  • Diabetic peripheral neuropathic pain (adults)
  • Fibromyalgia (adults)
  • Chronic musculoskeletal pain (adults)

Contraindications

  • Hypersensitivity to duloxetine
  • Use with MAOIs (within 14 days)
  • Use with linezolid or IV methylene blue
  • Uncontrolled narrow-angle glaucoma

Warnings & Precautions

  • Boxed Warning: Increased risk of suicidal thoughts and behavior in patients under 25 years
  • Hepatotoxicity: Monitor liver function, avoid in hepatic impairment
  • Serotonin syndrome: Risk with concurrent serotonergic drugs
  • Elevated blood pressure: Monitor blood pressure regularly
  • Activation of mania: Monitor in bipolar patients
  • Discontinuation syndrome: Taper gradually over ≥2 weeks

Drug Interactions

  • MAOIs: Contraindicated – minimum 5-day washout from duloxetine
  • CYP1A2 inhibitors: Increase duloxetine levels significantly
  • Thioridazine: Wait 5 days after duloxetine before starting
  • Anticoagulants: Increased bleeding risk
  • CYP2D6 substrates: Duloxetine inhibits CYP2D6

Adverse Reactions

Common (≥5%):

  • Nausea, dry mouth, somnolence, constipation
  • Decreased appetite, hyperhidrosis, dizziness

Serious:

  • Hepatotoxicity, serotonin syndrome, hypertensive crisis

Special Populations

  • Hepatic Impairment: Avoid use in any hepatic insufficiency
  • Renal Impairment: Avoid if CrCl <30 mL/min
  • Elderly: No dose adjustment needed, monitor closely
  • Pregnancy: Category C – use only if benefits outweigh risks
Medical Disclaimer: This information is for educational purposes only and is not intended as medical advice. Always consult with qualified healthcare professionals before making any treatment decisions. Individual patient circumstances may vary significantly.