What is the initial dosing of Cymbalta (duloxetine) for a patient with major depressive disorder or generalized anxiety disorder and normal renal and hepatic function?

Cymbalta (Duloxetine) Initial Dosing

For major depressive disorder and generalized anxiety disorder in adults with normal renal and hepatic function, start Cymbalta at 60 mg once daily, though initiating at 30 mg once daily for 1 week before increasing to 60 mg once daily is a reasonable alternative to reduce nausea. 1

Major Depressive Disorder (MDD)

Standard Initial Dosing

• The FDA-approved starting dosage is 40 mg/day (given as 20 mg twice daily) to 60 mg/day (given either once daily or as 30 mg twice daily). 1
• For some patients, starting at 30 mg once daily for 1 week allows adjustment to duloxetine before increasing to 60 mg once daily. 1
• The 60 mg once daily starting dose provides the best balance of efficacy and tolerability. 2

Tolerability Considerations

• Starting at 30 mg once daily for 1 week significantly reduces the rate of nausea (16.4% vs 32.9%) compared to starting at 60 mg once daily, with only transitory impact on effectiveness during the first week. 3
• After 2 weeks of treatment, patients who started at 30 mg once daily show no significant difference in effectiveness compared to those who started at 60 mg once daily. 3
• The most common adverse effect is nausea, which is reduced by administering 30 mg once daily for 1 week before increasing to 60 mg once daily. 4

Maximum Dosing

• While 120 mg/day has been shown effective, there is no evidence that doses greater than 60 mg/day confer additional benefits. 1

Generalized Anxiety Disorder (GAD)

Adults Under 65 Years

• Initiate duloxetine at 60 mg once daily. 1
• For some patients, starting at 30 mg once daily for 1 week before increasing to 60 mg once daily may be desirable to allow adjustment. 1
• While 120 mg once daily has been shown effective, there is no evidence that doses greater than 60 mg/day confer additional benefit. 1

Geriatric Patients (≥65 Years)

• Start at 30 mg once daily for 2 weeks before considering an increase to the target dose of 60 mg/day. 1
• If increasing beyond 60 mg once daily, use increments of 30 mg once daily, with a maximum studied dose of 120 mg per day. 1

Pediatric Patients (7-17 Years)

• Initiate at 30 mg once daily for 2 weeks before considering an increase to 60 mg once daily. 1
• The recommended dosage range is 30 to 60 mg once daily. 1

Administration Guidelines

Key Administration Points

• Administer orally with or without meals and swallow whole—do not chew, crush, or open the capsule. 1
• If a dose is missed, take it as soon as remembered unless it is almost time for the next dose; never take two doses at the same time. 1

Onset of Action

• Significant improvements in core emotional symptoms and painful physical symptoms are apparent after 1-2 weeks of treatment at 60 mg once daily. 5
• Duloxetine exhibits a shorter latency of action compared to some other antidepressants. 6

Common Pitfalls to Avoid

• Avoid starting at 60 mg once daily in patients with tolerability concerns—the higher initial dose is associated with increased discontinuation rates due to adverse events in some studies. 5
• Do not exceed 60 mg/day without clear rationale—higher doses do not provide additional benefit for most patients and are associated with higher rates of adverse reactions. 1
• The discontinuation rate due to adverse events (14.6%) is similar to selective serotonin reuptake inhibitors, with nausea being the most common reason for discontinuation. 2