From the Guidelines
Treatment for feet neuropathy should prioritize a multi-faceted approach, including first-line medications like gabapentin or pregabalin, proper foot care, and addressing the underlying cause, particularly diabetes, to improve quality of life and reduce morbidity and mortality. The most recent and highest quality study, 1, published in 2025, emphasizes the importance of a thorough assessment to ensure that neuropathy does not alter kinesthetic or proprioceptive sensation during physical activity. Key aspects of treatment include:
- First-line medications: anticonvulsants like gabapentin (starting at 300mg daily, gradually increasing to 300-600mg three times daily) or pregabalin (starting at 75mg twice daily, up to 300mg daily)
- Antidepressants: duloxetine (60mg daily) or amitriptyline (10-25mg at bedtime, increasing gradually) for pain management
- Proper foot care: inspecting feet daily, wearing comfortable shoes, and keeping blood sugar controlled if diabetes is the underlying cause
- Physical therapy and regular gentle exercise to improve symptoms and prevent complications
- Topical treatments: lidocaine patches or capsaicin cream for localized relief
- Transcutaneous electrical nerve stimulation (TENS) therapy as an additional option for pain relief. It is crucial to address the root cause of neuropathy, with diabetes being the most common, to achieve long-term management and improve health outcomes, as highlighted in 1 and 1.
From the FDA Drug Label
2.4 Dosage for Treatment of Diabetic Peripheral Neuropathic Pain in Adults Administer 60 mg once daily in adults with diabetic peripheral neuropathic pain. 14.4 Diabetic Peripheral Neuropathic Pain in Adults The efficacy of duloxetine delayed-release capsules for the management of neuropathic pain associated with diabetic peripheral neuropathy in adults was established in 2 randomized, 12-week, double-blind, placebo-controlled, fixed-dose trials in adult patients having diabetic peripheral neuropathic pain (DPNP) for at least 6 months (Study DPNP-1 and Study DPNP-2).
Treatment for feet neuropathy: The recommended dosage for the treatment of diabetic peripheral neuropathic pain, which includes feet neuropathy, is 60 mg once daily of duloxetine delayed-release capsules in adults 2.
From the Research
Treatment Options for Feet Neurapathy
- First-line treatments for painful diabetic peripheral neuropathy include duloxetine, gabapentin, amitriptyline, and pregabalin 3, 4, 5
- Nonopioid medications such as tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors, gabapentanoids, topicals, and transdermal substances are recommended as first-line therapy 6
- Topical lidocaine and transcutaneous electrical nerve stimulation are specifically suggested for focal peripheral neuropathic pain 4
- Combination therapy, tramadol, and tapentadol are recommended as second-line treatments 6, 3, 5
- Serotonin-specific reuptake inhibitors, anticonvulsants, NMDA antagonists, and interventional therapies are recommended as third-line treatments 6, 4
- Neurostimulation, low-dose opioids, and targeted drug delivery therapy are recommended as fourth-line, fifth-line, and sixth-line treatments, respectively 6
Non-Pharmacological Interventions
- Exercise and neuromodulation with spinal cord stimulation or transcutaneous electrical nerve stimulation have low- to moderate-quality evidence to support their use 3
- Acupuncture, alpha-lipoic acid, acetyl-L-carnitine, cannabidiol, and onabotulinumtoxinA need further study in patients with diabetic peripheral neuropathy 3, 5
- Peripheral transcutaneous electrical nerve stimulation is well tolerated and inexpensive, but benefits are modest 3
Comparison of Treatment Options
- The capsaicin 8% patch has similar efficacy to oral agents such as pregabalin, duloxetine, and gabapentin, but offers systemic tolerability benefits 7
- Oral agents such as pregabalin, gabapentin, duloxetine, and amitriptyline have a significantly elevated risk of somnolence, dizziness, fatigue, and discontinuation due to adverse events compared to placebo 7