What are the treatment options for peripheral neuropathy?

Treatment Options for Peripheral Neuropathy

Duloxetine and pregabalin are the first-line pharmacological treatments for peripheral neuropathy, particularly for diabetic peripheral neuropathy, as they are the only medications approved by both the FDA and European Medicines Agency for this indication. 1

First-Line Pharmacological Treatments

• Duloxetine (60-120 mg/day) - A serotonin-noradrenalin reuptake inhibitor that has demonstrated efficacy in reducing both painful and non-painful neuropathic symptoms 1, 2
• Pregabalin (300-600 mg/day) - An anticonvulsant that has shown efficacy in clinical trials for diabetic peripheral neuropathy, with benefits seen as early as week 1 of treatment 1, 3
• Tricyclic antidepressants (amitriptyline 25-75 mg/day, imipramine 25-75 mg/day) - Effective for neuropathic pain with a low NNT (1.5-3.5), but have significant anticholinergic side effects 1
• Gabapentin (900-3600 mg/day) - An alternative anticonvulsant that can be used for neuropathic pain 1, 2

Treatment Algorithm Based on Neuropathy Type

For Diabetic Peripheral Neuropathy:

1. Optimize glucose control - First step in management to prevent progression of neuropathy 1
2. First-line medications:
   • Start with either pregabalin or duloxetine 1
   • Pregabalin starting at lower doses (e.g., 75 mg twice daily) and titrating up to 300-600 mg/day 3
   • Duloxetine 60 mg once daily, may increase to 120 mg/day if needed 1
3. Second-line options if first-line fails or is not tolerated:
   • Tricyclic antidepressants (start at 10 mg/day in older patients, titrate up to 75 mg/day) 1
   • Venlafaxine (150-225 mg/day) 1
4. Third-line options:
   • Opioids such as tramadol (200-400 mg/day) or oxycodone (20-80 mg/day) for refractory cases 1
   • Topical capsaicin cream (0.075%) applied 3-4 times daily 1

For Chemotherapy-Induced Peripheral Neuropathy:

1. Early detection and dose adjustment of neurotoxic agents (e.g., bortezomib, thalidomide) 1
2. Duloxetine is the only treatment with strong evidence of benefit 2

Important Considerations and Caveats

• Monitor cardiac status with TCAs - ECG recommended before starting treatment, especially in older patients or those with cardiovascular disease; avoid doses >100 mg/day due to increased risk of sudden cardiac death 1
• Start low, go slow - Begin with lower doses, particularly in elderly patients, and titrate up gradually to minimize side effects 1, 2
• Common side effects to monitor:
  • Pregabalin: dizziness (21%), somnolence (12%), peripheral edema (9%), weight gain (4%) 3
  • Duloxetine: nausea, dizziness, somnolence, constipation 2
  • TCAs: anticholinergic effects (dry mouth, urinary retention, constipation), sedation 1
• Address underlying causes when possible - Check for vitamin B12 deficiency, hypothyroidism, alcohol use, toxin exposure, and other treatable causes 4, 5
• None of these treatments (except glycemic control) affect the natural history of diabetic peripheral neuropathy - they provide symptomatic relief only 1

Non-Pharmacological Approaches

• Lifestyle modifications - Diet and exercise 1
• Management of cardiovascular risk factors - Control of hypertension and hyperlipidemia 1
• Neuromodulation - Consider spinal cord stimulation or transcutaneous electrical nerve stimulation for refractory cases 6, 7

Monitoring and Follow-up

• Periodically reassess pain and health-related quality of life 2
• If partial pain relief is achieved with one agent, consider adding another first-line medication 2
• If inadequate pain relief occurs after an adequate trial, switch to an alternative first-line medication 2, 6