What are the common side effects of duloxetine (Cymbalta) and how are they managed?

Common Side Effects of Duloxetine (Cymbalta) and Their Management

Duloxetine commonly causes gastrointestinal and nervous system side effects including nausea, dry mouth, constipation, somnolence, dizziness, fatigue, decreased appetite, and increased sweating, which can typically be managed through dose adjustments, timing of administration, and supportive measures. 1

Most Common Side Effects

Duloxetine (Cymbalta), a serotonin and norepinephrine reuptake inhibitor (SNRI), has several well-documented side effects:

Gastrointestinal Effects

• Nausea - Most common side effect (23% vs 8% with placebo) 1
• Dry mouth (13% vs 5% with placebo) 1
• Constipation (9% vs 4% with placebo) 1
• Decreased appetite (7% vs 2% with placebo) 1
• Diarrhea (9% vs 6% with placebo) 1
• Vomiting (4% vs 2% in MDD/GAD trials) 1
• Abdominal pain (5% vs 4% with placebo) 1
• Acid reflux - A rare side effect reported in only 1.38% of patients 2

Neurological Effects

• Somnolence/sleepiness (10% vs 3% with placebo) 1
• Dizziness (9% vs 5% with placebo) 1
• Fatigue (9% vs 5% with placebo) 1
• Insomnia (9% vs 5% with placebo) 1
• Headache (14% vs 12% with placebo) 1
• Tremor (3% vs 1% in MDD/GAD trials) 1

Other Common Effects

• Hyperhidrosis (increased sweating) (6% vs 1% with placebo) 1
• Sexual dysfunction - Including erectile dysfunction (4% vs 1%), delayed ejaculation (2% vs 1%), decreased libido (3% vs 1%), and abnormal orgasm (2% vs <1%) 1

Serious but Less Common Side Effects

Cardiovascular Effects

• Blood pressure changes - Duloxetine may increase blood pressure or cause orthostatic hypotension 1
• Increased risk of falls, especially in the elderly 1

Psychiatric Effects

• Suicidal thinking and behavior (through age 24 years) 3
• Behavioral activation/agitation 3
• Hypomania or mania 3, 1

Other Serious Effects

• Serotonin syndrome - Life-threatening condition with symptoms including agitation, hallucinations, coma, coordination problems, racing heartbeat, sweating, fever, muscle rigidity, tremor, and seizures 1
• Abnormal bleeding - Especially if taken with warfarin, NSAIDs, or aspirin 1
• Severe skin reactions - Including erythema multiforme and Stevens-Johnson syndrome 3, 1
• Hepatic failure - Presenting as abdominal pain, hepatomegaly, elevated transaminases, and jaundice 3, 1
• Seizures 1
• Hyponatremia (low sodium levels) - More common in elderly 1
• Urinary problems - Including decreased urine flow 1
• Visual problems - Eye pain, vision changes, swelling or redness around the eye 1

Management of Side Effects

General Approaches

1. Start at lower doses - Begin with 30mg once daily for the first week to reduce nausea and other initial side effects 4
2. Take with food - May help reduce gastrointestinal side effects 1
3. Time of administration - Taking at bedtime may help manage somnolence-related side effects 5
4. Adequate hydration - For dry mouth and constipation 1
5. Gradual dose titration - To minimize side effects 1

Managing Specific Side Effects

Gastrointestinal Effects

• Nausea: Usually transient and improves within 1-2 weeks; taking with food may help 5
• Constipation: Increase fluid intake, dietary fiber, and physical activity; stool softeners if needed 1
• Dry mouth: Frequent sips of water, sugar-free gum or candies, artificial saliva products 1

Neurological Effects

• Dizziness/somnolence: Take at bedtime; avoid activities requiring alertness until effects are known 1
• Insomnia: Take in the morning; practice good sleep hygiene 1
• Headache: Over-the-counter analgesics as needed 1

Sexual Dysfunction

• Dose reduction if possible
• Timing of sexual activity (before daily dose)
• Consider adjunctive medications in consultation with healthcare provider 1

Increased Sweating

• Antiperspirants
• Layered clothing
• Dose reduction if severe 1

Discontinuation Management

Never stop duloxetine abruptly - Discontinuation syndrome may occur with symptoms including:

• Anxiety, irritability
• Fatigue, sleep problems
• Headache, dizziness
• Electric shock-like sensations
• Nausea, vomiting, diarrhea 1

Recommended approach: Taper slowly over at least 2 weeks when discontinuing 3, 1

Monitoring Recommendations

1. Blood pressure and pulse - Before starting and throughout treatment 3, 1
2. Liver function - Monitor for signs of liver damage (jaundice, right upper abdominal pain, dark urine) 3, 1
3. Mental status - Watch for emergence of suicidal thoughts, unusual behavior changes, or mania 1
4. Electrolytes - Consider monitoring sodium levels, especially in elderly patients 1

Important Precautions and Contraindications

• Absolutely contraindicated with MAOIs - Risk of serotonin syndrome 3, 1
• Use caution with CYP1A2 inhibitors (e.g., fluvoxamine) - Can increase duloxetine levels by up to 460% 6
• Smoking - May decrease duloxetine concentration by approximately 30% 6
• Severe hepatic impairment - Contraindicated 3, 1
• Severe renal impairment - Use with caution 1
• Avoid alcohol - May increase risk of liver injury 1

By understanding these common side effects and their management strategies, patients and healthcare providers can optimize duloxetine therapy while minimizing adverse effects.