What is the management and treatment of peripheral neuropathy?

Management and Treatment of Peripheral Neuropathy

First-Line Pharmacological Treatment

Duloxetine (60-120 mg/day) is the strongest evidence-based first-line treatment for painful peripheral neuropathy, particularly for chemotherapy-induced and diabetic peripheral neuropathy. 1, 2, 3

• Start duloxetine at 60 mg once daily; can increase to 120 mg if needed after 2-4 weeks 4, 3
• Number needed to treat (NNT) is 5.2 for 60 mg/day and 4.9 for 120 mg/day, meaning approximately 1 in 5 patients will achieve 50% pain relief 5, 4
• Duloxetine must be tapered slowly when discontinuing to avoid withdrawal symptoms 1, 2
• Duloxetine is contraindicated in patients with hepatic disease 5

Pregabalin (300-600 mg/day) is an equally effective first-line alternative, particularly for diabetic peripheral neuropathy 1, 5, 6

• Start at 150 mg daily in divided doses; maximum 600 mg daily 5, 4, 6
• NNT is 5.99 for 300 mg/day and 4.04 for 600 mg/day 5, 4
• Requires dose adjustment in renal impairment 5
• FDA-approved for neuropathic pain associated with diabetic peripheral neuropathy and spinal cord injury 6

Gabapentin (900-3600 mg/day) is another first-line option with similar efficacy to pregabalin but requires more frequent dosing 1, 2, 5

• Requires dose adjustment in renal impairment 5

Second-Line Pharmacological Options

Tricyclic antidepressants (TCAs) remain effective but have fallen out of favor due to side effects 1, 2, 5

• Amitriptyline 25-75 mg/day has an NNT of 1.5-3.5, showing high efficacy 1, 5, 4
• Nortriptyline and desipramine are alternatives with potentially fewer side effects 2
• Use with extreme caution in patients with cardiac disease, glaucoma, or orthostatic hypotension 2, 5, 4
• Start at 10 mg and increase gradually to 75 mg daily 4

Venlafaxine (150-225 mg/day) can be considered if duloxetine is not tolerated 1, 5

Tramadol (200-400 mg/day) is a second-line option with dual mechanism as a weak μ-opioid agonist 5

Topical Treatments for Localized Pain

Topical agents should be considered for localized peripheral neuropathic pain 5

• Lidocaine 5% patches for localized pain, particularly with allodynia 5
• Capsaicin 0.075% cream applied 3-4 times daily; pain may increase in first 2-3 weeks before relief 5, 4
• Menthol 1% cream applied twice daily may provide rapid relief 5
• Topical amitriptyline/ketamine preparations are NOT recommended based on a 462-patient trial showing no benefit 1

Treatment Algorithm

Step 1: Start with duloxetine 60 mg daily OR pregabalin 150-300 mg daily 2, 4

Step 2: Assess pain after 2-4 weeks; if partial relief, increase dose (duloxetine to 120 mg or pregabalin to 600 mg) 2, 4

Step 3: If inadequate relief after adequate trial, switch to alternative first-line medication (gabapentin or TCA) 2, 4

Step 4: If single agent provides partial relief, consider adding another first-line medication from different class 2, 5

Step 5: For refractory cases, consider topical agents or second-line medications 5, 4

Chemotherapy-Induced Peripheral Neuropathy (CIPN) Specific Management

For patients actively receiving neurotoxic chemotherapy who develop intolerable neuropathy: discuss dose delaying, dose reduction, or stopping chemotherapy 1

For established CIPN after chemotherapy completion: duloxetine is the ONLY treatment with strong evidence 1, 2

Do NOT offer these agents for CIPN prevention or treatment 1:

• Acetyl-L-carnitine (strong recommendation against; high-quality evidence of harm outweighing benefits) 1, 2
• Gabapentin/pregabalin for prevention (insufficient evidence) 1
• Oral cannabinoids (no benefit shown, increased toxicity) 1
• Topical amitriptyline/ketamine (no benefit in 462-patient trial) 1

Insufficient evidence to recommend for CIPN treatment (may consider in clinical trial context only) 1:

• Acupuncture (preliminary evidence suggests potential benefit) 1
• Scrambler therapy (mixed results in phase II trials) 1
• Exercise therapy (preliminary evidence suggests potential benefit) 1

Diabetic Peripheral Neuropathy Specific Considerations

Optimize glycemic control as the foundational intervention (HbA1c 6-7%) 1

• Poor or erratic glycemic control contributes to neuropathic pain genesis 1
• Address cardiovascular risk factors including hypertension and hyperlipidemia 1

First-line medications for diabetic neuropathy are duloxetine and pregabalin, both FDA-approved for this indication 1, 6, 3, 6

Critical Pitfalls and Caveats

Elderly patients require special precautions 5, 4:

• Start with lower doses and titrate more slowly
• Increased risk of falls with TCAs and gabapentinoids 4
• Monitor for orthostatic hypotension, confusion, and sedation 4

Strong opioids should generally be avoided due to risks of addiction, constipation, and lack of long-term efficacy data 5, 4

Monitor for common side effects 5, 4:

• Duloxetine: nausea, dry mouth, somnolence
• Pregabalin/gabapentin: weight gain, edema, dizziness, somnolence
• TCAs: anticholinergic effects, drowsiness, orthostatic hypotension, cardiac conduction abnormalities

Periodically reassess pain levels and quality of life to determine if medication adjustments are needed 2

Patients with pre-existing neuropathy are at higher risk for developing medication-induced or chemotherapy-induced neuropathy 2

Non-Pharmacological Approaches

Exercise and functional training can help reduce neuropathic symptoms 5, 4

Lifestyle modifications including blood sugar control, regular exercise, and weight management are crucial 4

Physical measures such as wearing loose-fitting shoes, cotton socks, and regular walking can improve circulation 4