Which is better for neuropathy, pregabalin or duloxetine, in an elderly patient with multiple myeloma?

Treatment of Chemotherapy-Induced Peripheral Neuropathy in Multiple Myeloma

Start with pregabalin 150 mg/day (50 mg three times daily or 75 mg twice daily) as first-line therapy for this elderly patient with bortezomib-induced neuropathy, reserving duloxetine as second-line treatment if pregabalin fails or is not tolerated. 1

Rationale for Pregabalin as First-Line

The European Myeloma Network guidelines specifically identify calcium channel blockers (gabapentin and pregabalin) alongside serotonin-norepinephrine reuptake inhibitors (duloxetine) as "very effective, especially in painful PN" for multiple myeloma patients. 1 However, the practical recommendations from myeloma-specific guidelines favor pregabalin as the initial agent. 1

The 2010 Haematologica guidelines explicitly recommend pregabalin 150-600 mg/day for at least three months as first-line therapy for bortezomib-induced peripheral neuropathy (BIPN), with duloxetine 30-60 mg/day positioned as a "valid second-line choice" after pregabalin failure. 1

Specific Dosing Algorithm for This Patient

Initial Phase (Weeks 1-2)

• Start pregabalin at 75 mg twice daily (150 mg/day total) 1
• In elderly patients, consider starting even lower at 50 mg three times daily to minimize dizziness and somnolence 2, 3
• Monitor for dose-dependent adverse effects including drowsiness, dizziness, and peripheral edema 1, 2

Titration Phase (Weeks 2-4)

• Increase to 150 mg twice daily (300 mg/day) if tolerated and pain persists 1, 3
• The American Academy of Neurology recommends allowing 2-4 weeks for adequate trial, including titration time plus 2 weeks at maximum tolerated dose 3

Optimization Phase (Weeks 4-12)

• If response is inadequate at 300 mg/day, escalate to 300 mg twice daily (600 mg/day maximum) 1, 4
• Higher doses above 300 mg/day are not consistently more effective and carry increased adverse effects, so use cautiously 2
• Continue for at least 3 months total before declaring treatment failure 1

When to Switch to Duloxetine

Switch to duloxetine 30-60 mg/day if: 1

• Pregabalin fails to provide adequate pain relief after 3 months at optimized doses
• Intolerable side effects occur (particularly excessive sedation or weight gain in this elderly patient)
• Patient has comorbid depression, as duloxetine provides dual benefit 1

The diabetic neuropathy literature shows duloxetine may be more effective than pregabalin for neuropathic pain intensity, but with a worse side effect profile (drowsiness 22-33%, vomiting 11%, headache 11%, dizziness 11% versus pregabalin's 4% drowsiness). 5 However, these data are from diabetic neuropathy, not myeloma-related neuropathy.

Combination Therapy Consideration

If pregabalin provides partial but insufficient relief, adding duloxetine to pregabalin may be considered rather than switching entirely. 6 A case report demonstrated successful treatment of paclitaxel-induced neuropathy using combination duloxetine plus pregabalin therapy. 6 However, this approach lacks guideline support and should be reserved for refractory cases.

Critical Pitfalls to Avoid in Elderly Patients

Renal function assessment is mandatory before initiating pregabalin. 2, 7 Both pregabalin and gabapentin are renally excreted, and elderly patients invariably have reduced renal function requiring dose adjustment. 2, 7 Calculate creatinine clearance using the Cockcroft-Gault equation. 7

Do not start at high doses (such as 300 mg twice daily immediately) without gradual titration, as this dramatically increases intolerable adverse effects in elderly patients. 2, 7

Do not declare treatment failure prematurely. Pregabalin requires at least 3 months of therapy at optimized doses to properly evaluate efficacy in BIPN. 1

Never abruptly discontinue either medication. Taper gradually to avoid withdrawal symptoms. 2

Adjunctive Measures

While pharmacologic therapy is being optimized, recommend tramadol for breakthrough chronic pain. 1 The guidelines also suggest non-pharmacologic measures including wearing loose-fitting shoes, keeping feet uncovered in bed, walking moderately, and soaking feet in cold water for temporary relief. 1

Monitoring Parameters

• Assess pain intensity using validated tools (Numerical Rating Scale or McGill Pain Questionnaire) at each dose adjustment 5
• Monitor for peripheral edema, weight gain, dizziness, and somnolence 1, 2
• Reassess at 2-4 weeks after reaching target dose, then monthly 3
• Grade neuropathy severity using Total Neuropathy Score if available 1