Common Side Effects of Duloxetine (Cymbalta)
Duloxetine commonly causes nausea, dry mouth, dizziness, somnolence, constipation, decreased appetite, increased sweating, and fatigue as its most frequent side effects. 1
Primary Side Effect Profile
Duloxetine (Cymbalta) is a selective serotonin and norepinephrine reuptake inhibitor (SSNRI) that is used for various conditions including depression, anxiety, diabetic peripheral neuropathy, and chronic musculoskeletal pain. The FDA-approved drug label provides the most comprehensive information about its side effect profile.
Most Common Side Effects:
- Nausea (most common)
- Dry mouth
- Sleepiness/somnolence
- Fatigue/asthenia
- Constipation
- Loss of appetite
- Increased sweating (hyperhidrosis)
- Dizziness 2, 1
Gastrointestinal Effects:
- Nausea and vomiting (can be reduced by starting at 30mg once daily for 1 week before increasing to 60mg) 2
- Abdominal pain or discomfort
- Diarrhea
- Constipation 1
Neurological Effects:
- Headache
- Dizziness
- Tremor
- Insomnia or somnolence 2
Cardiovascular and Metabolic Effects
Duloxetine requires careful monitoring for certain cardiovascular effects:
- Changes in blood pressure (both increases and decreases)
- Increased risk of falls, especially in elderly patients
- Sustained clinical hypertension 2, 1
Unlike tricyclic antidepressants, duloxetine does not seem to produce clinically important electrocardiographic changes, though blood pressure monitoring is still recommended 2.
Serious but Less Common Side Effects
Hepatic Effects:
- Liver damage (presenting as itching, right upper abdominal pain, dark urine, yellow skin/eyes)
- Elevated liver enzymes
- Hepatic failure (rare)
- Cholestatic jaundice (rare) 2, 1
Psychiatric Effects:
- Behavioral activation/agitation
- Hypomania or mania
- Suicidal thinking and behavior (through age 24 years) 2
Other Serious Adverse Effects:
- Serotonin syndrome (life-threatening condition with symptoms including agitation, hallucinations, coordination problems, racing heartbeat, fever)
- Abnormal bleeding (especially when combined with blood thinners or NSAIDs)
- Severe skin reactions (including Stevens-Johnson syndrome)
- Seizures (rare)
- Low sodium levels (especially in elderly) 1
Discontinuation Symptoms
Abrupt discontinuation of duloxetine can lead to withdrawal symptoms including:
- Anxiety
- Irritability
- Fatigue
- Sleep problems
- Headache
- Dizziness
- Electric shock-like sensations
- Gastrointestinal disturbances 1
Duloxetine should be tapered when treatment is being discontinued to avoid these symptoms 2.
Special Populations
Children and Adolescents:
- Similar side effects as adults
- May experience decreased weight and changes in height percentiles
- Weight and height should be monitored regularly 1
Elderly Patients:
- May experience more severe adverse effects
- Lower starting doses and more gradual titration recommended
- Higher risk for falls 2, 1
Rare Side Effects
Some case reports have identified unusual side effects:
- Acid reflux (reported in approximately 1.38% of patients) 3
- Dysosmia (smell disturbances) and dysgeusia (taste disturbances) 4
Monitoring Recommendations
- Monitor blood pressure before and throughout treatment
- Watch for signs of liver dysfunction
- Be alert for signs of serotonin syndrome, especially when combined with other serotonergic medications
- Monitor for increased bleeding risk if combined with anticoagulants or NSAIDs
- In children and adolescents, monitor height and weight regularly 1
Unlike some other antidepressants, aminotransferase monitoring is generally considered unnecessary for duloxetine according to some guidelines 2, though the FDA label still recommends monitoring for signs of liver dysfunction.
Duloxetine should not be used concurrently with MAOIs due to risk of serotonin syndrome, and caution should be exercised with drugs metabolized by CYP1A2 and CYP2D6 due to potential interactions 2.