What is the maximum dose of duloxetine (Cymbalta)?

From the Guidelines

The maximum recommended dose of duloxetine is 120 mg per day, as supported by the most recent and highest quality study 1.

Key Points to Consider

• The dose of 120 mg/day has shown efficacy in the treatment of pain associated with diabetic peripheral neuropathy (DPN) in multicenter randomized trials 1.
• Duloxetine also appeared to improve neuropathy-related quality of life, which is a crucial aspect of managing chronic conditions like DPN 1.
• Adverse events may be more severe in older people but may be attenuated with lower doses and slower titration of duloxetine 1.
• It is essential to start treatment at a lower dose, typically 30-60 mg daily, and gradually increase as needed to minimize side effects.
• Common side effects include nausea, dry mouth, constipation, decreased appetite, fatigue, sleepiness, and increased sweating.
• Patients with severe renal impairment or hepatic insufficiency may require lower maximum doses, and the medication should be used with caution in these populations.

Important Considerations for Duloxetine Use

• Duloxetine should be tapered gradually when discontinuing to avoid withdrawal symptoms.
• The medication works by inhibiting the reuptake of serotonin and norepinephrine in the brain, which helps regulate mood, pain perception, and anxiety.
• Given the potential for adverse effects, especially in older adults, careful monitoring and dose adjustment are necessary to ensure the safe use of duloxetine.
• The use of duloxetine in patients with diabetes should also consider the potential small increase in A1C reported in longer-term studies 1.

From the FDA Drug Label

2.2 Dosage for Treatment of Major Depressive Disorder in Adults The recommended starting dosage in adults with MDD is 40 mg/day (given as 20 mg twice daily) to 60 mg/day (given either once daily or as 30 mg twice daily) For some patients, it may be desirable to start at 30 mg once daily for 1 week, to allow patients to adjust to duloxetine delayed-release capsules before increasing to 60 mg once daily. While a 120 mg/day dose was shown to be effective, there is no evidence that doses greater than 60 mg/day confer any additional benefits

2.3 Dosage for Treatment of Generalized Anxiety Disorder Recommended Dosage in Adults Less than 65 Years of Age For most adults less than 65 years of age with GAD, initiate duloxetine delayed-release capsules 60 mg once daily For some patients, it may be desirable to start at 30 mg once daily for 1 week, to allow patients to adjust to duloxetine delayed-release capsules before increasing to 60 mg once daily. While a 120 mg once daily dosage was shown to be effective, there is no evidence that doses greater than 60 mg/day confer additional benefit Nevertheless, if a decision is made to increase the dosage beyond 60 mg once daily, increase dosage in increments of 30 mg once daily.

The maximum dose studied was 120 mg per day

The maximum dose of duloxetine is 120 mg per day 2.

From the Research

Maximum Dose of Duloxetine

The maximum dose of duloxetine varies depending on the indication and patient population.

• For generalized anxiety disorder (GAD), the maximum dose is 120 mg once daily 3.
• For major depressive disorder (MDD), the maximum dose is 120 mg/day, which can be administered as 60 mg twice daily or 120 mg once daily 4, 5, 6.
• For diabetic peripheral neuropathic pain, the maximum dose is 60 mg twice daily or 120 mg once daily 4.
• For stress urinary incontinence, the maximum dose is 80 mg/day, administered as 40 mg twice daily 4.

Dose Escalation

Dose escalation of duloxetine from 60 mg/day to 120 mg/day has been studied, and results suggest that it is safe and tolerable 6.

• The majority of adverse events were mild and transient, and occurred in the first week of duloxetine dosing (at 60 mg once daily).
• Long-term treatment at a stabilized duloxetine dose was associated with a relatively low incidence of treatment-emergent adverse events and treatment discontinuation due to adverse events.

Pharmacokinetics

The pharmacokinetics of duloxetine are influenced by various factors, including patient demographics, concomitant medications, and hepatic and renal function 7.

• The elimination half-life of duloxetine is approximately 10-12 hours, and the volume of distribution is approximately 1640 L.
• Impaired hepatic function or severely impaired renal function may require specific warnings or dose recommendations.
• Concomitant use of CYP1A2 inhibitors, such as fluvoxamine, can increase duloxetine exposure to a clinically significant degree.