What is the management of peripheral neuropathy?

Management of Peripheral Neuropathy

For painful peripheral neuropathy, start with duloxetine 60 mg daily, pregabalin 150-300 mg daily, or gabapentin 900-3600 mg daily as first-line therapy, with tricyclic antidepressants as an alternative if these are not tolerated. 1, 2

Address Underlying Causes First

• Control blood glucose aggressively in diabetic patients, as poor glycemic control directly contributes to neuropathy progression and severity 3, 4
• Check and correct vitamin B12 deficiency, which is a common treatable cause of peripheral neuropathy 4, 5
• Manage cardiovascular risk factors including elevated blood pressure and obesity, as these contribute to neuropathy development 3, 4
• Screen for hypothyroidism with thyroid-stimulating hormone levels, as this is among the most common treatable causes 5

First-Line Pharmacological Treatment for Painful Neuropathy

Duloxetine (SNRI):

• Start at 60 mg once daily, can increase to 120 mg daily if needed 1, 2, 6
• Number needed to treat (NNT) is 5.2 for 60 mg/day and 4.9 for 120 mg/day, meaning approximately 1 in 5 patients achieve 50% pain relief 1, 2
• FDA-approved specifically for diabetic peripheral neuropathic pain 6
• Contraindicated in hepatic disease 1

Pregabalin:

• Start at 150 mg daily, titrate to 300-600 mg daily in divided doses 1, 2, 7
• NNT is 5.99 for 300 mg/day and 4.04 for 600 mg/day 1, 2
• FDA-approved for neuropathic pain associated with diabetic peripheral neuropathy 7
• Requires dose adjustment in renal impairment 1

Gabapentin:

• Dose range 900-3600 mg/day in divided doses 1, 2
• Similar efficacy to pregabalin but requires more frequent dosing 1
• Requires dose adjustment in renal impairment 1

Tricyclic Antidepressants (TCAs):

• Amitriptyline or nortriptyline 25-75 mg/day 3, 1, 2
• NNT of 1.5-3.5, showing high efficacy but more side effects than newer agents 1, 2
• Use with caution in elderly patients and those with cardiac disease, glaucoma, or orthostatic hypotension 1, 2
• Contraindicated in patients at risk of falls 2

Topical Treatments for Localized Pain

• Lidocaine 5% patches for localized peripheral neuropathic pain, particularly with allodynia, with minimal systemic effects 1, 4
• Capsaicin 0.075% cream applied 3-4 times daily; warn patients that pain may increase in first 2-3 weeks before relief is achieved 1, 2
• Topical menthol 1% cream applied twice daily may provide rapid relief 1

Second-Line Treatment Options

• Add another first-line agent from a different class if initial therapy provides inadequate relief 1, 2
• Venlafaxine 150-225 mg/day if duloxetine is not tolerated 1, 4
• Tramadol 200-400 mg/day as a weak μ-opioid agonist with dual mechanism 3, 1
• Opioids (morphine, oxycodone) should generally be avoided due to addiction risk, constipation, and lack of long-term safety data 3, 4

Non-Pharmacological Approaches

• Exercise and functional training can reduce neuropathic symptoms 1, 4
• Alpha-lipoic acid 600 mg IV daily for 3 weeks has shown efficacy in diabetic neuropathy 3, 1
• Transcutaneous electrical nerve stimulation (TENS) is well-tolerated and inexpensive with modest benefits 4
• Spinal cord stimulation may be considered in extreme cases unresponsive to pharmacotherapy 3

Special Populations and Dosing Considerations

Elderly Patients:

• Start with lower doses and titrate more slowly due to increased risk of side effects and falls 1, 2
• TCAs carry particular risk in this population 1, 2

Renal Impairment:

• Adjust gabapentin and pregabalin doses appropriately 1

Hepatic Disease:

• Duloxetine is contraindicated 1

Treatment Algorithm

1. Start with duloxetine 60 mg daily OR pregabalin 150 mg daily 1, 2
2. Assess pain after 2-4 weeks using numerical pain rating scale 2
3. If inadequate relief: Increase dose (duloxetine to 120 mg, pregabalin to 300-600 mg) OR switch to another first-line medication 1, 2
4. If still inadequate: Add topical agent for localized pain OR add second first-line agent from different class 1, 2
5. Monitor for: Pain levels, side effects, weight gain, edema, blood pressure 2

Critical Pitfalls to Avoid

• Do not use strong opioids long-term due to addiction risk and adverse effects 3, 1, 4
• Avoid acetyl-L-carnitine due to lack of evidence for benefit 2
• Do not use venlafaxine for prevention of chemotherapy-induced neuropathy, as recent evidence does not support this 3
• Watch for anticholinergic effects with TCAs including drowsiness, dry mouth, urinary retention, and orthostatic hypotension 1, 2
• Be aware that most trials lasted less than 6 months, so long-term efficacy and safety data are limited 3, 4