What are the side effects of duloxetine (Serotonin-Norepinephrine Reuptake Inhibitor - SNRI)?

Duloxetine Side Effects

Duloxetine (Cymbalta) is associated with numerous side effects ranging from common gastrointestinal disturbances to rare but serious hepatic and dermatological reactions, requiring careful monitoring and patient education. 1, 2, 3

Common Side Effects

• Gastrointestinal effects: Nausea (most common), dry mouth, abdominal discomfort, vomiting, diarrhea, and constipation 1, 2, 3
• Neurological effects: Dizziness, headache, tremor, insomnia, and somnolence 1, 2, 3
• Other common effects: Diaphoresis (excessive sweating), decreased appetite, weight loss (particularly in pediatric patients), and fatigue 1, 2, 3
• Cardiovascular effects: Increased blood pressure and increased pulse, requiring regular monitoring 1, 2

Serious Adverse Effects

Psychiatric and Neurological

• Suicidal thinking and behavior: Increased risk, particularly in patients through age 24 years 1, 2, 3
• Behavioral activation/agitation: May occur, especially early in treatment 1, 2
• Hypomania/mania: Can be triggered in susceptible individuals 1, 2
• Seizures: Rare but serious potential complication 1, 2, 3
• Discontinuation syndrome: Characterized by anxiety, irritability, headache, dizziness, electric shock-like sensations, and gastrointestinal disturbances when stopping duloxetine abruptly 1, 2, 3

Hepatic

• Hepatic failure: Can present as abdominal pain, hepatomegaly, and elevated transaminase levels 1, 2
• Cholestatic jaundice: Requires immediate discontinuation of duloxetine 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, 3
• Hypersensitivity reactions: Characterized by blisters, peeling rash, mucosal erosions requiring immediate discontinuation 1, 2, 3

Other Serious Effects

• Sexual dysfunction: Including decreased sexual desire and performance 2, 4
• Abnormal bleeding: Especially when combined with NSAIDs, aspirin, or warfarin 2, 3
• Serotonin syndrome: Life-threatening condition with symptoms including agitation, hallucinations, coma, coordination problems, racing heartbeat, high or low blood pressure, sweating, fever, nausea, vomiting, diarrhea, muscle rigidity, dizziness, flushing, tremor, and seizures 3

Drug Interactions

• MAOIs: Concomitant use is contraindicated due to increased risk of serotonin syndrome 1, 2, 3
• CYP1A2 and CYP2D6 substrates: Duloxetine may interact with drugs metabolized by these enzymes 1, 2, 5
• Medications affecting bleeding risk: Increased risk of bleeding when combined with NSAIDs, aspirin, or warfarin 2, 3
• Other serotonergic drugs: Including triptans, tricyclics, lithium, buspirone, SSRIs, SNRIs - increased risk of serotonin syndrome 3

Special Populations

Pediatric Patients

• Growth effects: Decreased appetite and weight loss have been observed; monitor height and weight regularly 3
• Discontinuation symptoms: Headache, dizziness, insomnia, and abdominal pain are common 3

Elderly Patients

• Increased sensitivity: May be more sensitive to adverse effects, particularly hyponatremia 2
• Fall risk: Increased risk of falls due to blood pressure changes and dizziness 3

Monitoring Recommendations

• Blood pressure and pulse: Regular monitoring is recommended 1, 2
• Hepatic function: Monitor for signs of liver dysfunction 1, 2
• Weight and height: Regular monitoring in pediatric patients 3
• Discontinuation: Should be done slowly (over at least 2 weeks) to avoid withdrawal symptoms 1, 2, 4

Rare Side Effects

• Acid reflux: Reported in approximately 1.38% of patients 6
• Extrapyramidal disorder: Reported in post-marketing surveillance 3
• Angle-closure glaucoma: Reported in post-marketing surveillance 3
• Hyperprolactinemia and galactorrhea: Reported in post-marketing surveillance 3

Efficacy vs. Side Effects

• For chronic pain conditions including diabetic neuropathic pain, duloxetine at 60 mg daily is effective but associated with more side effects than lower doses 1, 7
• The number needed to treat for benefit (NNTB) is 5 for diabetic peripheral neuropathy and 8 for fibromyalgia, indicating moderate efficacy 7
• Approximately 16% of patients discontinue duloxetine due to adverse effects 7

Important Precautions

• Pregnancy: Should be carefully considered as it may affect the newborn 2
• Breastfeeding: Duloxetine passes into breast milk and may harm the baby 3
• Alcohol use: Concomitant use with heavy alcohol intake may be associated with severe liver injury 3
• Driving/operating machinery: May affect ability to make decisions, think clearly, or react quickly 3