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

Duloxetine Side Effects

Duloxetine commonly causes gastrointestinal effects (nausea, dry mouth, abdominal discomfort), neurological symptoms (dizziness, headache, somnolence), and cardiovascular changes (increased blood pressure and pulse), with several potentially serious adverse effects including hepatic failure, severe skin reactions, and serotonin syndrome. 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 (increased sweating), decreased appetite, weight loss, and fatigue 1, 2, 3
• Cardiovascular effects: Increased blood pressure and increased pulse 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: May present as abdominal pain, hepatomegaly, and elevation of transaminase levels 1, 2
• Cholestatic jaundice: Requires immediate discontinuation 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, and seizures 3
• Low sodium levels: Particularly in elderly patients, presenting with headache, weakness, confusion, and memory problems 3
• Urination problems: Including decreased urine flow or inability to pass urine 3
• Visual problems: Including eye pain, vision changes, and swelling or redness around the eye 3
• Acid reflux: A rare adverse effect reported in approximately 1.38% of patients 5

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
• Blood thinners: Increased risk of bleeding when combined with warfarin, NSAIDs, or aspirin 3
• Other serotonergic drugs: Increased risk of serotonin syndrome when combined with triptans, tricyclics, lithium, buspirone, SSRIs, or other SNRIs 3

Special Populations

Elderly Patients

• More sensitive to adverse effects, particularly hyponatremia 2
• Increased risk of falls, especially when starting duloxetine or increasing the dose 3

Children and Adolescents

• Common side effects include nausea, decreased weight, and dizziness 3
• Height and weight should be monitored during treatment 3

Monitoring Recommendations

• Blood pressure and pulse: Regular monitoring is recommended 1, 2
• Hepatic function: Monitor for signs of liver dysfunction 1, 2
• Discontinuation: Should be done slowly (over at least 2 weeks) to avoid withdrawal symptoms 2, 6

Important Precautions

• Abrupt discontinuation: Avoid stopping duloxetine suddenly to prevent discontinuation syndrome 1, 3
• Alcohol use: Avoid heavy alcohol consumption as it may be associated with severe liver injury 3
• Driving and operating machinery: Duloxetine can cause sleepiness and affect decision-making ability 3
• Pregnancy and breastfeeding: Duloxetine passes into breast milk and may affect the newborn 2, 3

Most adverse events with duloxetine are mild to moderate in severity 4, 6, with nausea being the most common reason for discontinuation in clinical trials 7. While duloxetine has a similar adverse effect profile to other SNRIs, its unique hepatic and dermatological risks require special attention and monitoring 1, 2.