What are the side effects of duloxetine (Cymbalta)?

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From the Guidelines

Duloxetine can cause a range of side effects, including common issues like nausea, dry mouth, and dizziness, as well as more serious problems such as liver damage, serotonin syndrome, and severe skin reactions, as noted in a 2020 clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders 1.

Common Side Effects

The most frequently encountered side effects of duloxetine include:

  • Diaphoresis
  • Dry mouth
  • Abdominal discomfort
  • Nausea
  • Vomiting
  • Diarrhea
  • Dizziness
  • Headache
  • Tremor
  • Insomnia
  • Somnolence
  • Decreased appetite
  • Weight loss

Serious Side Effects

More severe and potentially life-threatening side effects associated with duloxetine are:

  • Sustained clinical hypertension
  • Increased blood pressure
  • Increased pulse
  • Suicidal thinking and behavior (through age 24 years)
  • Behavioral activation/agitation
  • Hypomania
  • Mania
  • Sexual dysfunction
  • Seizures
  • Abnormal bleeding
  • Serotonin syndrome
  • Hepatic failure presenting as abdominal pain, hepatomegaly, and elevation of transaminase levels
  • Cholestatic jaundice
  • Severe skin reactions, including erythema multiforme and Stevens-Johnson syndrome

Special Considerations

Duloxetine should be discontinued and not restarted in patients who develop jaundice or other evidence of clinically significant liver dysfunction, and at the first appearance of blisters, peeling rash, mucosal erosions, or other signs of hypersensitivity 1. Additionally, concomitant administration of duloxetine and MAOIs is contraindicated due to the increased risk of serotonin syndrome. Duloxetine may also interact with drugs metabolized by CYP1A2 and CYP2D6.

From the FDA Drug Label

Duloxetine delayed-release capsules may cause serious side effects, including:

  1. liver damage.
  2. changes in blood pressure and falls.
  3. Serotonin Syndrome:
  4. abnormal bleeding:
  5. severe skin reactions:
  6. discontinuation symptoms:
  7. manic episodes:
  8. visual problems:
  9. seizures or convulsions
  10. low salt (sodium) levels in the blood. The most common side effects of duloxetine delayed-release capsules include: nausea dry mouth sleepiness fatigue constipation loss of appetite increased sweating dizziness

Duloxetine side effects include serious and common possible side effects.

  • Serious side effects include:
    • Liver damage
    • Changes in blood pressure and falls
    • Serotonin Syndrome
    • Abnormal bleeding
    • Severe skin reactions
    • Discontinuation symptoms
    • Manic episodes
    • Visual problems
    • Seizures or convulsions
    • Low salt (sodium) levels in the blood
  • Common side effects include:
    • Nausea
    • Dry mouth
    • Sleepiness
    • Fatigue
    • Constipation
    • Loss of appetite
    • Increased sweating
    • Dizziness 2

From the Research

Common Side Effects of Duloxetine

  • Nausea, which is often cited as the primary reason for discontinuation of duloxetine in trials 3
  • Dry mouth 4
  • Dizziness 4
  • Headache 4
  • Dysosmia (distorted sense of smell) and dysgeusia (distorted sense of taste) have been reported in a case study 4

Serious Side Effects

  • Increases in blood pressure, although these have been mild 3
  • Patients with a creatinine clearance of <30 mL/min and patients with hepatic impairment should avoid duloxetine due to potential serious side effects 3

Pharmacology and Interactions

  • Duloxetine is eliminated primarily in the urine after extensive hepatic metabolism by multiple oxidative pathways, methylation and conjugation 5
  • Duloxetine would not be expected to cause clinically significant inhibition of the metabolic clearance of drugs metabolised by P450 (CYP)3A, (CYP)1A2, (CYP)2C9, or (CYP)2C19, but would be expected to cause some inhibition of CYP 2D6 5
  • Duloxetine should not be used in combination with CYP 1A2 inhibitors or nonselective, irreversible monoamine oxidase inhibitors 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Duloxetine: a balanced and selective norepinephrine- and serotonin-reuptake inhibitor.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2005

Research

Safety and adverse event profile of duloxetine.

Expert opinion on drug safety, 2005

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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