When do you prescribe duloxetine (Cymbalta) for patients?

Indications for Duloxetine Prescription

Duloxetine should be prescribed for neuropathic pain conditions (particularly diabetic peripheral neuropathy), fibromyalgia, chronic musculoskeletal pain (including osteoarthritis and chronic low back pain), and chronic pelvic pain, with a recommended starting dose of 30 mg daily for one week before increasing to 60 mg daily for optimal efficacy and tolerability. 1, 2

Primary Indications

Neuropathic Pain

• Diabetic Peripheral Neuropathy: First-line treatment at 60 mg daily, with evidence showing consistent efficacy and pain reduction of ≥50% in many patients 1, 2
• Postherpetic Neuralgia: Effective when used with pregabalin or gabapentin, though pregabalin is FDA-approved specifically for this condition 1
• General Neuropathic Pain: Considered a first-line agent alongside tricyclic antidepressants and gabapentinoids 1

Fibromyalgia

• Effective at 60 mg daily with significant improvements in pain, function, and quality of life 2, 3
• Particularly beneficial when fibromyalgia co-occurs with depression 2
• FDA-approved for this indication with demonstrated efficacy in multiple clinical trials 4

Chronic Musculoskeletal Pain

• Osteoarthritis: Effective for pain management, particularly in older patients (>65 years) and those with knee osteoarthritis 1
• Chronic Low Back Pain: Provides small to moderate improvements in pain and function 1, 2
• 60 mg daily dosing is as effective as 120 mg daily with fewer side effects 2

Chronic Pelvic Pain

• Alternative to tricyclic antidepressants when they are not tolerated or effective 5
• Particularly useful when pelvic pain has a neuropathic component 5

Dosing Considerations

Initiation and Titration

• Start at 30 mg once daily for one week to reduce nausea (most common side effect) 1
• Increase to 60 mg once daily after one week, which is the optimal therapeutic dose for most indications 1, 2
• 60 mg daily is generally as effective as 120 mg daily with fewer side effects 2, 4

Special Populations

• Elderly: Use with caution, particularly in those over 65 years, though it may be more effective for osteoarthritis in this population 1
• Renal Impairment: Dosage adjustment required based on creatinine clearance 2
• Cardiovascular Disease: Generally safer than TCAs in patients with cardiac disease, with minimal impact on ECG or blood pressure 1

Monitoring and Adverse Effects

Common Side Effects

• Nausea (most common, can be reduced by starting at lower dose) 1, 6
• Dry mouth, headache, constipation, dizziness, and fatigue 7
• Sedation and weight gain (less common than with some other medications) 1

Precautions

• Avoid in combination with CYP1A2 inhibitors 6
• Use caution with medications metabolized by CYP2D6 7
• Monitor for changes in blood pressure, cognitive effects, and sedation 5
• Approximately 16% of patients may discontinue due to side effects 3, 8

Clinical Decision-Making Algorithm

1. Confirm diagnosis requiring duloxetine (neuropathic pain, fibromyalgia, chronic musculoskeletal pain)
2. Check contraindications:
   • Concomitant use of MAOIs
   • Uncontrolled narrow-angle glaucoma
   • Severe hepatic impairment
3. Assess comorbidities:
   • If patient has comorbid depression or anxiety, duloxetine may provide dual benefit 2
   • If patient has cardiovascular disease, duloxetine is preferred over TCAs 1
4. Initiate therapy:
   • Start at 30 mg daily for one week
   • Increase to 60 mg daily maintenance dose
5. Evaluate response:
   • Assess pain reduction after 4-6 weeks
   • If partial response, continue for additional 2-4 weeks
   • If inadequate response (<30% reduction), consider switching to alternative first-line agent 1

Key Clinical Pearls

• Pain relief may begin as early as one week but full effect may take 6-8 weeks 2, 4
• Duloxetine should not be abruptly discontinued; taper gradually to prevent withdrawal symptoms 7
• The 60 mg once-daily dosing simplifies treatment compared to some alternatives that require multiple daily doses 1
• Consider duloxetine particularly when pain coexists with depression or anxiety for potential dual benefit 2