What topical medication can be used for nighttime neuropathy of the toes?

Topical Medications for Nighttime Neuropathy of the Toes

For nighttime neuropathy of the toes, lidocaine 5% patches are the preferred topical treatment, applied for up to 12 hours before bedtime, as they are specifically effective for nocturnal neuropathic foot pain. 1

First-Line Topical Treatment

Lidocaine 5% patches should be applied to the affected toes/feet for up to 12 hours (but not exceeding 12 hours in a 24-hour period) before sleep. 1 The American Diabetes Association specifically notes that lidocaine patches may be particularly useful for individuals with nocturnal neuropathic foot pain, though they acknowledge limited data and note these patches are not effective for more widespread pain distribution. 1

• Up to 3 patches may be worn on the dorsal or plantar surface of the feet. 1
• The patches deliver lidocaine gradually over hours, which is more effective than cream or ointment formulations for sustained nighttime relief. 1
• Over-the-counter 4% lidocaine patches are available, though prescription 5% strength may be more effective. 1
• No systemic absorption or lidocaine toxicity has been reported with proper use. 1

Second-Line Topical Option: Capsaicin

If lidocaine patches are ineffective or contraindicated, capsaicin can be considered, though it requires consistent daytime application rather than nighttime-only use. 1

High-Concentration Capsaicin (8% Patch - FDA Approved)

The 8% capsaicin patch is FDA-approved for diabetic peripheral neuropathy and provides the strongest evidence for efficacy. 1, 2

• Applied for 30-60 minutes under medical supervision, with effects lasting up to 90 days. 2
• Requires pretreatment with topical lidocaine 4% for 60 minutes to reduce application discomfort. 2
• Can be reapplied after 90 days if pain returns. 2
• Provides sustained pain reduction from the second week through 8-12 weeks after a single application. 2

Low-Concentration Capsaicin Cream (0.075%)

Low-concentration capsaicin cream (0.075%) should be applied 3-4 times daily for at least 6-8 weeks to assess efficacy. 1, 2, 3

• The FDA-approved formulation is capsaicin 0.035-0.075%. 3
• Apply a thin film to affected toes and gently rub in until fully absorbed. 3
• Wash hands thoroughly with soap and water immediately after application (unless treating hands). 3
• Initial burning sensation typically resolves with continued use. 2
• Evidence for low-concentration capsaicin is weaker than for the 8% patch, with some studies showing it may not be meaningfully different from placebo. 4

Third-Line Compounded Options

If first and second-line treatments fail, compounded topical medications may be considered:

Amitriptyline 1-2% with ketamine 0.5-5% cream applied up to 3 times daily. 1

• This combination blocks sodium channels (amitriptyline) and antagonizes N-methyl-D-aspartate receptors (ketamine). 1
• In case series, 75% of patients with erythromelalgia noted improvement. 1
• Requires preparation at a compounding pharmacy. 1
• If ineffective, ketamine concentration can be increased up to 5%. 1

Important Clinical Considerations

Any topical treatment should be tried for at least 4 weeks before switching to assess true efficacy. 1, 2

Common Pitfalls to Avoid:

• Do not use lidocaine patches for more than 12 hours in a 24-hour period due to regulatory restrictions. 1
• Avoid excessive cooling of affected areas after capsaicin application, as this may interfere with efficacy. 2
• Patients with more severe and longer duration of disease tend to respond less well to topical treatments. 1
• Local skin reactions (burning, erythema) are common with capsaicin but usually tolerable and attenuate with time; the number needed to harm is 2.5. 1, 2

When Topical Treatments Are Most Appropriate:

Topical treatments are best suited for localized neuropathic pain and for patients with contraindications to oral pharmacotherapy or who prefer topical treatments. 1, 2

• If pain is widespread rather than localized to the toes, systemic medications (pregabalin, duloxetine, gabapentin) may be more appropriate. 1
• Topical treatments cause fewer systemic adverse effects compared to oral medications. 1