What are the side effects of Cymbalta (duloxetine)?

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Cymbalta (Duloxetine) Side Effects

Cymbalta (duloxetine) has numerous common side effects including nausea, dry mouth, headache, and dizziness, as well as potentially serious adverse effects such as hepatic failure, severe skin reactions, and serotonin syndrome that require immediate medical attention. 1

Common Side Effects

  • Gastrointestinal effects: Nausea, dry mouth, abdominal discomfort, vomiting, diarrhea, constipation 1, 2
  • Neurological effects: Dizziness, headache, tremor, insomnia, somnolence 1, 2
  • Other common effects: Diaphoresis (excessive sweating), decreased appetite, weight loss, fatigue 1, 2
  • Cardiovascular effects: Increased blood pressure, increased pulse 1, 2

Serious Adverse Effects

Psychiatric and Neurological

  • Suicidal thinking and behavior: Particularly in patients through age 24 years 1, 2
  • Behavioral activation/agitation: May occur especially early in treatment 1, 2
  • Hypomania or mania: Can trigger manic episodes in susceptible individuals 1, 2
  • Seizures: Rare but serious potential complication 1, 2
  • Serotonin syndrome: Life-threatening condition with symptoms including agitation, hallucinations, coordination problems, racing heartbeat, high or low blood pressure, fever, muscle rigidity, and dizziness 2
  • Discontinuation syndrome: Symptoms include anxiety, irritability, headache, dizziness, electric shock-like sensations, and gastrointestinal disturbances when stopping duloxetine abruptly 1, 2

Hepatic

  • Hepatic failure: Presenting as abdominal pain, hepatomegaly, and elevation of transaminase levels 1, 2
  • Cholestatic jaundice: Duloxetine should be discontinued if jaundice or other evidence of clinically significant liver dysfunction develops 1, 2

Dermatological

  • Severe skin reactions: Including erythema multiforme and Stevens-Johnson syndrome 1, 2
  • Hypersensitivity reactions: Discontinue at first appearance of blisters, peeling rash, mucosal erosions, or other signs of hypersensitivity 1, 2

Other Serious Effects

  • Sexual dysfunction: May affect sexual desire and performance 1, 2
  • Abnormal bleeding: Especially when combined with NSAIDs, aspirin, or warfarin 1, 2
  • Hyponatremia: Low sodium levels, especially in elderly patients 2
  • Visual problems: Eye pain, changes in vision, swelling or redness around the eye 2

Drug Interactions

  • MAOIs: Concomitant use is contraindicated due to increased risk of serotonin syndrome 1, 2
  • CYP1A2 and CYP2D6 substrates: Duloxetine may interact with drugs metabolized by these enzymes 1, 2
  • Serotonergic drugs: Increased risk of serotonin syndrome when combined with other serotonergic agents like triptans, SSRIs, other SNRIs 2, 3
  • Metoclopramide: Contraindicated with duloxetine use 3
  • NSAIDs: May increase bleeding risk 2, 3

Special Populations

Pediatric Patients

  • Growth effects: Decreased appetite and weight loss have been observed in pediatric patients 2
  • Height changes: Regular monitoring of weight and height is recommended in pediatric patients 2

Elderly Patients

  • Higher sensitivity: May be more sensitive to adverse effects, particularly hyponatremia 2
  • Dosing considerations: May require lower doses and slower titration 1

Monitoring Recommendations

  • Cardiovascular monitoring: Regular monitoring of blood pressure and pulse 1, 2
  • Hepatic function: Monitor for signs of liver dysfunction 1, 2
  • Mental status: Monitor for worsening depression, suicidal thoughts, or unusual changes in behavior 2
  • Discontinuation: Taper slowly when discontinuing to avoid withdrawal symptoms 1, 2

Important Precautions

  • Alcohol use: Avoid heavy alcohol use while taking duloxetine as it may be associated with severe liver injury 2
  • Driving and operating machinery: May cause sleepiness or affect ability to make decisions, think clearly, or react quickly 2
  • Pregnancy: Use during pregnancy should be carefully considered as it may affect the newborn 1, 2

Despite these potential side effects, duloxetine is generally well-tolerated when appropriately prescribed and monitored, with most adverse events being mild to moderate in severity 4, 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Adverse reactions to duloxetine in depression.

Expert opinion on drug safety, 2011

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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