What is the treatment for neuropathy?

Treatment for Neuropathy

Duloxetine is the only medication with Level I evidence and should be the first-line pharmacological treatment for neuropathic pain, particularly for chemotherapy-induced peripheral neuropathy (CIPN), with demonstrated efficacy in reducing both painful and non-painful symptoms. 1, 2

First-Line Pharmacological Treatment

Duloxetine (Preferred)

• Start with 60 mg/day, may increase to 120 mg/day based on response and tolerability 3, 2
• Number needed to treat (NNT) of 5.2 for 60 mg/day and 4.9 for 120 mg/day 3, 4
• Must be tapered slowly when discontinuing to avoid withdrawal symptoms 1, 2
• Contraindicated in patients with hepatic disease 3

Alternative First-Line Options (When Duloxetine Not Tolerated)

Pregabalin:

• Start 150 mg/day (75 mg twice daily), titrate to 300-600 mg/day 3, 5
• NNT of 5.99 for 300 mg/day and 4.04 for 600 mg/day 4
• Adjust dose in renal impairment 3, 5
• Evaluate pain reduction after 2-4 weeks; consider successful if ≥30% reduction from baseline 4

Gabapentin:

• Start 100-300 mg at night or three times daily, maximum 3600 mg/day 3, 4
• Similar efficacy to pregabalin but requires more frequent dosing 3
• Note: Evidence for gabapentinoids in CIPN is weak and waning 1

Tricyclic Antidepressants (TCAs):

• Amitriptyline 25-75 mg/day 3
• NNT of 1.5-3.5, but more side effects than newer agents 3
• Use with caution in cardiac disease, glaucoma, or orthostatic hypotension 3, 2
• Current enthusiasm for TCAs in CIPN is declining due to lack of positive randomized trials and unfavorable side effects 1

Topical Treatments for Localized Neuropathic Pain

• Topical menthol 1% cream applied twice daily provides rapid relief 1, 3
• Topical lidocaine 5% patches for localized pain with allodynia 3
• Topical capsaicin 0.075% applied three to four times daily 3
• Topical amitriptyline/ketamine/baclofen combinations lack strong evidence and are not FDA-approved; enthusiasm has waned 1

Second-Line Treatment Options

If first-line medications provide inadequate relief after adequate trial:

• Add another first-line agent from a different class 3, 2
• Venlafaxine 150-225 mg/day (alternative SNRI if duloxetine not tolerated) 1, 3
• Note: Longer follow-up data do not support venlafaxine for prevention of neuropathy 1
• Tramadol 200-400 mg/day (weak μ-opioid agonist with dual mechanism) 1, 3
• Strong opioids can be considered but should generally be avoided due to addiction risks 1, 3

Non-Pharmacological Approaches (Recommended)

• Physical exercise and functional training (including vibration training) reduces CIPN symptoms 1
• Medical exercise to improve muscular strength and sensorimotor functions 1
• Acupuncture may be considered in selected patients 1
• Scrambler therapy shows suggestive benefit but needs further research 1

Prevention Strategies (Limited Evidence)

• No effective drug exists to prevent CIPN 1
• Cryotherapy with frozen socks and gloves can be considered, particularly for taxane therapy 1
• Compression therapy using surgical gloves may be considered 1

Special Populations

Elderly Patients:

• Start with lower doses and titrate more slowly due to increased risk of side effects 3, 4

Renal Impairment:

• Adjust gabapentin and pregabalin doses accordingly 3, 5

IgM-Related Neuropathy:

• Consider plasmapheresis for aggressive or progressing neuropathy 1, 2
• Single-agent rituximab for mild, slowly progressive neuropathy 1, 2
• Rituximab-based combinations for moderate to severe cases 1

Medications NOT Recommended

• Acetyl-L-carnitine is not recommended based on negative trial results 1, 2
• Venlafaxine for prevention (despite initial promise) 1
• Topical amitriptyline/ketamine without baclofen 1

Common Pitfalls and Caveats

• Regular assessment of CIPN enables early detection before neuropathy becomes irreversible 1
• Many neuropathic pain medications have significant dose-dependent side effects that may limit use 1, 2
• Patients with pre-existing neuropathy are at higher risk for medication-induced neuropathy 2
• When stopping duloxetine, always taper slowly to avoid withdrawal symptoms 1, 2
• Treatment approaches should focus on reduction or relief of neuropathic pain when patients experience chronic CIPN 1