What are the side effects of duloxetine (Cymbalta)?

Side Effects of Duloxetine

Duloxetine commonly causes gastrointestinal and neurological side effects, with nausea being the most frequent adverse effect, but also carries serious risks including hepatic failure, serotonin syndrome, and increased suicidality in young patients that require careful monitoring. 1, 2

Common Side Effects

Gastrointestinal Effects

• Nausea is the most common side effect, occurring frequently enough to be the leading cause of treatment discontinuation 2, 3
• Dry mouth, constipation, diarrhea, vomiting, and abdominal discomfort are common gastrointestinal complaints 1, 2
• Decreased appetite and weight loss occur, particularly important in pediatric populations 2
• Acid reflux has been reported, though rare (1.38% of patients) 4

Neurological Effects

• Dizziness, headache, somnolence, and insomnia are frequently reported 5, 1, 2
• Tremor may occur during treatment 1
• Fatigue and asthenia are common complaints 1, 2

Other Common Effects

• Increased sweating (hyperhidrosis) is a characteristic side effect related to norepinephrine reuptake inhibition 1, 2
• Sexual dysfunction, including decreased libido and performance, occurs commonly 1, 2
• Cardiovascular effects include increased blood pressure and pulse 1, 2

Serious Adverse Effects

Psychiatric Risks

• Duloxetine carries a black box warning for increased risk of suicidal thinking and behavior, particularly in patients through age 24 years 1, 2
• Behavioral activation or agitation may occur, especially early in treatment 1
• Hypomania or mania can be triggered in susceptible individuals 1
• Hallucinations and aggression have been reported post-marketing 2

Hepatic Toxicity

• Hepatic failure is a serious potential complication, presenting with abdominal pain, hepatomegaly, elevated transaminases, and jaundice 1, 2
• Duloxetine is contraindicated in patients with severe hepatic impairment 5
• The medication should be discontinued immediately if jaundice or clinically significant liver dysfunction develops 1

Serotonin Syndrome

• This life-threatening condition can occur, especially when combined with MAOIs, SSRIs, SNRIs, triptans, tramadol, or other serotonergic agents 1, 2
• Symptoms include agitation, hallucinations, coordination problems, muscle twitching, racing heartbeat, blood pressure changes, hyperthermia, muscle rigidity, and seizures 2
• Concomitant use with MAOIs is absolutely contraindicated 1, 2

Cardiovascular Effects

• Blood pressure increases can occur, requiring monitoring before and throughout treatment 2
• Orthostatic hypotension with dizziness and fainting may occur, particularly when initiating treatment or increasing doses 2
• Increased fall risk, especially in elderly patients 2
• Supraventricular arrhythmias have been reported post-marketing 2

Bleeding Risk

• Abnormal bleeding or bruising can occur, especially when combined with NSAIDs, aspirin, or warfarin 1, 2
• This reflects serotonergic effects on platelet function 2

Severe Dermatological Reactions

• Erythema multiforme and Stevens-Johnson syndrome are rare but serious complications 1
• Hypersensitivity reactions with blisters, peeling rash, mucosal erosions, urticaria, or cutaneous vasculitis require immediate discontinuation 1, 2

Ophthalmologic Effects

• Angle-closure glaucoma can occur, presenting with eye pain, vision changes, and periorbital swelling or redness 2
• Patients at risk should undergo preventative eye examination 2

Other Serious Effects

• Seizures or convulsions may occur 2
• Hyponatremia, particularly in elderly patients 2
• Urinary retention or difficulty urinating 2
• Acute pancreatitis has been reported post-marketing 2

Discontinuation Syndrome

• Abrupt discontinuation causes withdrawal symptoms in up to 30% of patients 6
• Symptoms include anxiety, irritability, headache, dizziness, electric shock-like sensations, nausea, vomiting, diarrhea, insomnia, and fatigue 2
• Taper slowly over at least two weeks to minimize withdrawal effects 2, 6

Special Population Considerations

Pediatric Patients

• Weight loss and decreased appetite are particularly concerning in children and adolescents 2
• Height and weight should be monitored regularly during treatment 2
• Mean weight decrease of 0.1 kg at 10 weeks versus 0.9 kg gain with placebo 2

Elderly Patients

• Greater sensitivity to adverse effects, particularly hyponatremia and falls 1
• Lower doses and slower titration recommended 1

Pregnancy and Breastfeeding

• Duloxetine passes into breast milk and may harm the infant 2
• Pregnancy should be carefully considered when prescribing 1

Drug Interactions

• CYP2D6 moderate inhibitor: use caution with drugs metabolized by this pathway, particularly those with narrow therapeutic index 2, 7
• Avoid concomitant use with potent CYP1A2 inhibitors (ciprofloxacin, enoxacin) 2, 7
• Contraindicated with thioridazine due to serious cardiac arrhythmia risk 2

Monitoring Requirements

• Blood pressure and pulse should be monitored before starting and throughout treatment 1, 2
• Hepatic function monitoring for signs of liver dysfunction 1
• Weight and height in pediatric patients 2
• Mental status for suicidality, especially in young adults 1, 2

Important Clinical Pearls

• Most adverse effects are mild to moderate and transient, occurring early in treatment 5, 3
• Nausea is dose-related and often improves with continued use 3
• Duloxetine should not be combined with heavy alcohol use due to severe liver injury risk 2
• The medication can be taken with or without food 2
• Do not open, crush, or chew capsules as this affects drug delivery 2