What are the side effects and adverse effects of duloxetine (Cymbalta)?

Side Effects and Adverse Effects of Duloxetine (Cymbalta)

Duloxetine commonly causes gastrointestinal and nervous system side effects including nausea, dry mouth, somnolence, constipation, dizziness, and decreased appetite, with more serious but rare adverse effects including hepatic failure, severe skin reactions, and serotonin syndrome. 1, 2

Common Side Effects

Duloxetine, a serotonin and norepinephrine reuptake inhibitor (SNRI), is associated with numerous common side effects:

• Gastrointestinal effects:

  • Nausea (23% vs 8% with placebo)
  • Dry mouth (13% vs 5% with placebo)
  • Constipation (9% vs 4% with placebo)
  • Diarrhea (9% vs 6% with placebo)
  • Abdominal discomfort/pain (5% vs 4% with placebo)
  • Vomiting (4% vs 2% with placebo)

• Neurological effects:

  • Headache (14% vs 12% with placebo)
  • Somnolence/sedation (10% vs 3% with placebo)
  • Dizziness (9% vs 5% with placebo)
  • Fatigue (9% vs 5% with placebo)
  • Insomnia (9% vs 5% with placebo)

• Other common effects:

  • Hyperhidrosis/increased sweating (6% vs 1% with placebo)
  • Decreased appetite (7% vs 2% with placebo)
  • Sexual dysfunction (including decreased libido, erectile dysfunction, delayed ejaculation)
  • Tremor (3% vs 1% with placebo)

2

Serious Adverse Effects

While less common, duloxetine can cause several serious adverse effects that require monitoring:

Hepatic Effects

• Hepatic failure presenting as abdominal pain, hepatomegaly, and elevated transaminases
• Cholestatic jaundice
• Important: Discontinue duloxetine immediately and do not restart if jaundice or other evidence of clinically significant liver dysfunction develops 1

Dermatologic Reactions

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

Cardiovascular Effects

• Increased blood pressure and pulse
• Sustained clinical hypertension
• Risk of falls, especially in elderly patients 2

Neuropsychiatric Effects

• Suicidal thinking and behavior (particularly in patients through age 24 years)
• Behavioral activation/agitation
• Hypomania or mania
• Seizures 1, 2

Hematologic Effects

• Abnormal bleeding risk, especially when combined with NSAIDs, aspirin, or warfarin 2

Other Serious Concerns

• Serotonin syndrome (agitation, hallucinations, coma, coordination problems, racing heartbeat, fluctuating blood pressure, hyperthermia, etc.)
• Low sodium levels, especially in elderly patients 2
• Discontinuation syndrome if stopped abruptly (anxiety, irritability, headache, dizziness, electric shock-like sensations, insomnia, etc.) 2

Special Populations

Children and Adolescents

• Duloxetine is the only SNRI with FDA indication for generalized anxiety disorder in children and adolescents 7 years and older
• Additional monitoring needed for:
  • Weight loss (16% of pediatric patients had clinically significant weight decrease)
  • Height changes (monitor regularly)
  • Increased risk of suicidal thinking and behavior 1, 2

Elderly Patients

• Increased risk of falls and hyponatremia
• Duloxetine may be more effective for osteoarthritis pain in patients >65 years than younger patients 1

Drug Interactions

• Contraindicated with MAOIs due to risk of serotonin syndrome
• May interact with drugs metabolized by CYP1A2 and CYP2D6
• Use caution with:
  • Triptans
  • Other antidepressants (SSRIs, SNRIs, tricyclics)
  • Tramadol and fentanyl
  • Amphetamines
  • Warfarin
  • NSAIDs 1, 2

Discontinuation Considerations

• Never stop duloxetine abruptly
• Taper slowly over at least 2 weeks to avoid discontinuation syndrome
• Monitor for symptoms like anxiety, irritability, headache, dizziness, electric shock-like sensations, insomnia, and nausea 1, 2

Monitoring Recommendations

• Blood pressure and pulse: Regular monitoring, especially in patients with hypertension or cardiac disease
• Hepatic function: Be alert for signs of liver dysfunction
• Mental status: Monitor for emergence of suicidal thoughts, behavioral activation, or mania
• Weight and height (in pediatric patients)
• No specific laboratory tests are routinely recommended 1

Pitfalls to Avoid

• Abrupt discontinuation: Always taper slowly
• Alcohol use: Avoid heavy alcohol consumption while taking duloxetine due to risk of severe liver injury
• Overlooking drug interactions: Particularly with MAOIs, which are absolutely contraindicated
• Missing early signs of serious reactions: Promptly discontinue if signs of liver dysfunction or severe skin reactions appear
• Inadequate monitoring in patients with pre-existing hypertension or cardiac disease

Duloxetine is generally well-tolerated, but careful patient selection, appropriate dosing, and vigilant monitoring are essential to minimize adverse effects and optimize outcomes.