What is the treatment for polyneuropathy?

Treatment of Polyneuropathy

The first-line pharmacological treatment for polyneuropathy includes pregabalin, duloxetine, or gabapentin, which are recommended as initial treatments for neuropathic pain associated with polyneuropathy. 1

Approach to Treatment

Treatment of polyneuropathy involves two main strategies:

1. Disease-modifying therapy (when possible):

   • Optimize glucose control in diabetic polyneuropathy to prevent or delay development (type 1 diabetes) and slow progression (type 2 diabetes) 1
   • For ATTRv amyloidosis polyneuropathy, TTR silencers (patisiran, inotersen, vutrisiran) can slow progression and potentially reverse disease 1
   • Treat underlying causes when identified (metabolic, inflammatory, toxic, etc.) 2

2. Symptomatic management (for all types):

   • Pharmacological treatment for neuropathic pain
   • Management of autonomic symptoms
   • Physical therapy and lifestyle modifications

Pharmacological Management of Neuropathic Pain

First-line medications:

• Pregabalin: Starting dose 75mg at bedtime, with gradual weekly increase to maximum 600mg daily (divided doses) 1, 3

  • FDA-approved for diabetic peripheral neuropathy and postherpetic neuralgia 3
  • Demonstrated efficacy in clinical trials with statistically significant improvement in pain scores 3

• Duloxetine: 60mg once daily 1, 4

  • FDA-approved for diabetic peripheral neuropathic pain 4
  • Shown to improve endpoint mean pain scores and increase proportion of patients with ≥50% reduction in pain 4

• Gabapentin: Start with 600mg single dose on day 1, increase every 3 days to 1800mg divided in 3 doses, maximum 3600mg daily 1

  • Effective for diabetic neuralgia and postherpetic neuralgia 1

Second-line medications:

• Tricyclic antidepressants: Effective for neuropathic pain but may have increased side effects in patients with autonomic symptoms 1, 2
• Tramadol: Can be used at 50mg once or twice daily, gradually increasing to maximum 400mg daily 1
• Mexiletine: A sodium channel blocker (225-675mg/day) for refractory cases 1

Management of Autonomic Symptoms

For patients with autonomic dysfunction:

• Increased salt/fluid intake 1
• Salt tablets 1
• Fludrocortisone 1
• Midodrine 1
• Droxidopa 1
• Pyridostigmine (less risk of fluid retention) 1
• Compression stockings and abdominal binders 1

Note: These medications may be poorly tolerated in patients with cardiac involvement or restrictive physiology 1

Special Considerations for Specific Types

Diabetic Polyneuropathy

• Annual assessment for all patients with type 2 diabetes and patients with type 1 diabetes for ≥5 years 1
• Assessment should include history and testing of small-fiber function (temperature/pinprick) and large-fiber function (vibration/monofilament) 1
• 10-g monofilament testing to identify feet at risk for ulceration 1

Amyloid Polyneuropathy

• TTR silencers (patisiran, inotersen, vutrisiran) for ATTRv amyloidosis 1
• Vitamin A supplementation (3,000 IU daily) needed with TTR silencers 1
• Monitor for medication-specific side effects:
  • Patisiran: Infusion reactions (premedication recommended)
  • Inotersen: Thrombocytopenia and glomerulonephritis (regular monitoring required) 1

Immune-Mediated Polyneuropathy

• Consider IVIG for acute inflammatory demyelinating polyneuropathy (AIDP) 1
• Steroids may be beneficial for mild peripheral neuropathy, especially in immune-related cases 1

Non-Pharmacological Approaches

• Physical therapy: Important for maintaining function and preventing complications 5
• Cardio-exercise: At least 30 minutes twice weekly to help with pain relief through inhibition of pain pathways 1
• Foot care: Essential for preventing complications, especially in diabetic polyneuropathy 5
• Nutritional interventions: Increasing omega-3 to omega-6 fatty acid ratio may help regulate inflammation 1

Common Pitfalls and Caveats

• Diagnostic delay: Polyneuropathy is a diagnosis of exclusion; non-diabetic neuropathies may be treatable and should be identified 1
• Undertreatment: Up to 50% of diabetic peripheral neuropathy may be asymptomatic but still requires preventive care 1
• Medication side effects: Older patients with amyloidosis are at greater risk for side effects; consider the Beers Criteria for potentially inappropriate medications in older adults 1
• Autonomic symptoms: May be overlooked but require specific management strategies 1
• Inadequate follow-up: Regular monitoring is essential, especially for progression and medication side effects 2

Remember that early diagnosis and treatment can stop progression and improve symptoms in most cases of polyneuropathy 6. A timely diagnosis of the cause is a prerequisite for appropriate specific treatment 7.