What is the recommended dose of Duloxetine (Cymbalta)?

From the Guidelines

Duloxetine should be started at a dose of 30 mg once daily for one week before increasing to the target dose of 60 mg once daily. This gradual titration helps minimize initial side effects like nausea and dizziness, as recommended by various studies, including those published in the Mayo Clinic Proceedings 1 and American Family Physician 1.

Key Considerations for Duloxetine Dosing

• For depression, the recommended dose is 60 mg once daily, though some patients may require up to 120 mg daily (given as 60 mg twice daily) 1.
• For anxiety disorders, 60 mg once daily is standard 1.
• For diabetic peripheral neuropathic pain and fibromyalgia, 60 mg once daily is effective, though some patients begin with 30 mg daily for one week before increasing 1.
• For chronic musculoskeletal pain, 60 mg once daily is recommended 1.

Administration and Precautions

• Duloxetine should be taken at the same time each day, with or without food, and the capsule should be swallowed whole.
• Patients with severe renal impairment or hepatic insufficiency require lower doses, as indicated in studies 1.
• Discontinuation should involve gradual tapering to prevent withdrawal symptoms, a precaution highlighted in various guidelines 1.
• Common side effects include nausea, dry mouth, constipation, decreased appetite, fatigue, sleepiness, and increased sweating, as noted in the clinical practice update on management of chronic gastrointestinal pain 1.

Mechanism of Action

Duloxetine works by inhibiting the reuptake of serotonin and norepinephrine, increasing their availability in the brain and helping regulate mood, pain perception, and anxiety, as explained in the context of its use for neuropathic pain management 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)

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

2.4 Dosage for Treatment of Diabetic Peripheral Neuropathic Pain in Adults Administer 60 mg once daily in adults with diabetic peripheral neuropathic pain.

2.5 Dosage for Treatment of Fibromyalgia The recommended duloxetine delayed-release capsules dosage is 60 mg once daily in adults with fibromyalgia.

2.6 Dosage for Treatment of Chronic Musculoskeletal Pain in Adults The recommended duloxetine delayed-release capsules dosage is 60 mg once daily in adults with chronic musculoskeletal pain.

The recommended duloxetine dose varies by condition:

• Major Depressive Disorder (MDD): 40-60 mg/day
• Generalized Anxiety Disorder (GAD): 60 mg once daily
• Diabetic Peripheral Neuropathic Pain: 60 mg once daily
• Fibromyalgia: 60 mg once daily
• Chronic Musculoskeletal Pain: 60 mg once daily 2

From the Research

Duloxetine Dose

• The recommended dose of duloxetine is 60-120 mg once daily for the treatment of generalized anxiety disorder (GAD) 3.
• Duloxetine 60-120 mg once daily was effective in preventing or delaying relapse in responders to duloxetine in a longer-term study 3.
• The pharmacokinetics of duloxetine in healthy volunteers were dose proportional over the range of 40-120 mg once daily 3.
• Steady state was typically reached by day 3 of administration, and duloxetine may be administered without regard to food or time of day 3.
• Higher duloxetine doses (up to 120 mg/day) have been studied using a twice-daily dosing schedule, and rapid dose escalation of duloxetine (60 mg/day --> 90 mg/day --> 120 mg/day) is safe and tolerable 4.

Factors Affecting Duloxetine Dose

• Patient demographic characteristics, such as sex, smoking status, age, ethnicity, cytochrome P450 (CYP) 2D6 genotype, hepatic function, and renal function, may influence the pharmacokinetics of duloxetine 5.
• Impaired hepatic function or severely impaired renal function warrant specific warnings or dose recommendations 5.
• Concomitant use of duloxetine and potent CYP1A2 inhibitors should be avoided, and duloxetine should be used with caution in patients receiving drugs that are extensively metabolized by CYP2D6 3, 5.

Efficacy and Safety of Duloxetine

• Duloxetine has demonstrated efficacy for the treatment of major depressive disorder, generalized anxiety disorder, neuropathic pain, fibromyalgia, and stress urinary incontinence 6.
• The dual mechanism of duloxetine benefits the treatment of comorbid clinical conditions, and supports the efficacy, safety, and tolerability of duloxetine in short- and long-term treatments 6.
• Duloxetine may be an effective treatment for mood spectrum disorders, panic disorder, several symptom clusters of borderline personality, and as add-on drug in schizophrenia 7.