What are the indications for Cymbalta (duloxetine)?

Cymbalta (Duloxetine) Indications

Cymbalta is FDA-approved for five distinct indications: major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain (including chronic low back pain and osteoarthritis). 1

FDA-Approved Indications

Major Depressive Disorder (MDD)

• Approved for treatment of major depressive disorder in adults 1
• Efficacy established in four short-term trials and one maintenance trial 1
• Requires prominent depressed or dysphoric mood present nearly every day for at least 2 weeks, interfering with daily functioning, plus at least 5 of 9 DSM criteria symptoms 1

Generalized Anxiety Disorder (GAD)

• Approved for GAD in adults and children/adolescents aged ≥7 years 2, 1
• Duloxetine is the only SNRI with FDA indication for any anxiety disorder in pediatric patients 2
• Efficacy demonstrated in three short-term trials and one maintenance trial in adults 1
• Indicated when excessive anxiety and worry are present more days than not for at least 6 months, difficult to control, and associated with at least 3 of 6 symptoms (restlessness, fatigue, concentration difficulty, irritability, muscle tension, sleep disturbance) 1

Diabetic Peripheral Neuropathic Pain (DPNP)

• Approved for management of neuropathic pain associated with diabetic peripheral neuropathy 3, 1
• Doses of 60 mg and 120 mg daily showed efficacy in multicenter randomized trials 3
• Considered a first-line medication for painful diabetic peripheral neuropathy 4
• Duloxetine improved neuropathy-related quality of life in addition to pain reduction 3

Fibromyalgia (FM)

• FDA-approved for management of fibromyalgia 5, 6, 1
• Associated with small to moderate improvements in pain, function, and quality of life 5
• Recommended as first-line therapy by multiple guidelines 6

Chronic Musculoskeletal Pain

• Approved for chronic musculoskeletal pain, established in studies of chronic low back pain and chronic pain due to osteoarthritis 5, 1
• For chronic low back pain with insufficient response to nonpharmacologic approaches like exercise, duloxetine demonstrates small improvements 5, 7
• For osteoarthritis affecting multiple joints or incompletely controlled with topical NSAIDs, duloxetine can be used 5

Dosing by Indication

Standard Dosing Regimens

• MDD: Start 40-60 mg/day; target 40-60 mg/day (acute treatment); maintenance 60 mg/day; maximum 120 mg/day 1
• GAD: Start 60 mg/day; target 60 mg once daily; maximum 120 mg/day 1
• DPNP: Start and target 60 mg once daily; maximum 60 mg/day 1
• Fibromyalgia: Start 30 mg/day; target 60 mg once daily; maximum 60 mg/day 1
• Chronic Musculoskeletal Pain: Start 30 mg/day; target 60 mg once daily; maximum 60 mg/day 1

Practical Dosing Considerations

• To minimize nausea (the most common adverse effect), start at 30 mg once daily for 1 week before increasing to 60 mg once daily 4
• Duloxetine has sufficiently long elimination half-life (approximately 10-12 hours) to permit single daily dosing 2, 8
• Can be administered without regard to food or time of day 1
• Capsules must be swallowed whole—do not chew, crush, open, or mix contents with food or liquids 1

Off-Label Uses Supported by Guidelines

Neuropathic Pain (Non-Diabetic)

• First-line medication for peripheral neuropathic pain conditions 4
• However, duloxetine has NOT been studied in neuropathic pain conditions other than diabetic peripheral neuropathy, so efficacy in other types is unknown 4

Anxiety Disorders in Children and Adolescents

• Recommended for social anxiety, generalized anxiety, separation anxiety, and panic disorders in patients 6-18 years old 2

Critical Safety Considerations

Contraindications

• Concomitant use with MAOIs or within close temporal proximity is absolutely contraindicated due to serotonin syndrome risk 2, 1
• Uncontrolled narrow-angle glaucoma 1

Serious Warnings

• Black box warning: Increased risk of suicidal thinking and behavior in children, adolescents, and young adults (through age 24) taking antidepressants for MDD and other psychiatric disorders 1
• Hepatotoxicity: Hepatic failure (sometimes fatal) has been reported; discontinue immediately if jaundice or clinically significant liver dysfunction develops 2, 1
• Should not be prescribed to patients with substantial alcohol use or evidence of chronic liver disease 1
• Severe skin reactions: Erythema multiforme and Stevens-Johnson syndrome can occur; discontinue at first appearance of blisters, peeling rash, mucosal erosions, or hypersensitivity signs 2, 1

Common Adverse Effects

• Nausea (most common), dry mouth, constipation, dizziness, headache, somnolence, decreased appetite, weight loss, diaphoresis 2
• Sustained clinical hypertension, increased blood pressure, and increased pulse have been reported 2
• Monitor height, weight, pulse, and blood pressure; no specific laboratory tests recommended 2

Discontinuation

• A gradual dose reduction is mandatory to avoid discontinuation syndrome 2, 1
• Discontinuation symptoms reported following missed doses or acute cessation 2
• Alternate-day dosing during tapering is NOT recommended as it causes pronounced receptor occupancy variation and likely increases withdrawal risk 9

Drug Interactions

• Avoid concomitant use with potent CYP1A2 inhibitors (e.g., fluvoxamine), which can increase duloxetine exposure by 460% 8
• Duloxetine may interact with drugs metabolized by CYP1A2 and CYP2D6 2
• Smoking is associated with 30% decrease in duloxetine concentration 8
• Use caution with drugs affecting coagulation (NSAIDs, aspirin, anticoagulants) due to increased bleeding risk 1

Special Populations

• Avoid in patients with creatinine clearance <30 mL/min 10
• Avoid in patients with hepatic impairment 10
• Adverse events may be more severe in older adults but can be attenuated with lower doses and slower titration 3