What are the recommended adjunctive treatments for neuropathy?

Recommended Adjunctive Treatments for Neuropathic Pain

The first-line adjunctive treatments for neuropathic pain are pregabalin, duloxetine, and gabapentin, with topical lidocaine recommended for localized peripheral neuropathic pain. 1

First-Line Pharmacological Options

Anticonvulsants

• Pregabalin (300-600 mg/day in divided doses) is FDA-approved for diabetic peripheral neuropathy, postherpetic neuralgia, and neuropathic pain associated with spinal cord injury 2
• Start pregabalin at a low dose (25-50 mg/day in older adults, 75 mg twice daily in others) and titrate slowly ("low and slow" approach) to minimize side effects 3, 1
• Gabapentin (900-3600 mg/day in divided doses) is effective for various neuropathic pain syndromes, with treatment initiated at 300 mg/day and titrated up to effective dose 4, 5
• Both medications require dose adjustment in patients with renal impairment 2, 6

Antidepressants

• Duloxetine (60-120 mg/day) is FDA-approved for diabetic peripheral neuropathy and shows consistent efficacy 1
• Tricyclic antidepressants (TCAs) such as amitriptyline or nortriptyline (25-75 mg/day) are effective with an NNT of 1.5-3.5 1
• Start TCAs at low doses (10 mg/day) in older adults and titrate carefully due to anticholinergic side effects 1
• Use TCAs with caution in patients with cardiovascular disease and avoid doses >100 mg/day due to increased risk of sudden cardiac death 1

Topical Treatments

• Topical lidocaine (5% patch) is recommended as first-line therapy for localized peripheral neuropathic pain, especially in older adults or those with renal impairment 6, 1
• Capsaicin cream (0.075%) applied 3-4 times daily can provide relief for some patients 1, 6

Treatment Algorithm

1. Initial Selection:

   • For localized peripheral neuropathic pain: Start with topical lidocaine 6, 1
   • For widespread neuropathic pain: Start with either pregabalin, duloxetine, or gabapentin 1

2. Titration and Monitoring:

   • Start with low doses and titrate slowly based on response and tolerability 3, 1
   • For pregabalin: Begin with 75 mg twice daily, increase to 150 mg twice daily within 1 week, maximum 300 mg twice daily 2
   • For gabapentin: Start at 300 mg/day, increase to 900 mg/day by day 3, then titrate to 1800-3600 mg/day as needed 4, 5
   • For duloxetine: Start with 60 mg once daily 1

3. Inadequate Response:

   • If partial pain relief after adequate trial, add another first-line medication 1
   • If no significant pain relief (<30% reduction) after adequate trial, switch to alternative first-line medication 1

Special Considerations

• Renal Impairment: Reduce doses of gabapentin and pregabalin; consider topical lidocaine as first choice 6, 2
• Older Adults: Start with lower doses and titrate more slowly; be vigilant for side effects 1, 6
• Cardiovascular Disease: Use TCAs with caution; monitor ECG if necessary 1

Common Side Effects and Management

• Pregabalin/Gabapentin: Dizziness (19%), somnolence (14%), peripheral edema (7%), and gait disturbance (14%) 5

  • Consider asymmetric dosing with larger dose in evening to minimize daytime sedation 3
  • Most side effects are transient and resolve within approximately 10 days 4, 7

• Duloxetine: Nausea, dizziness, somnolence, constipation 1

  • Take with food to reduce gastrointestinal side effects

• TCAs: Dry mouth, orthostatic hypotension, constipation, urinary retention 1

  • Secondary amine TCAs (nortriptyline, desipramine) have fewer anticholinergic effects 1

Pitfalls to Avoid

• Suboptimal dosing is common - ensure adequate trial with appropriate dose titration before concluding treatment failure 3, 4
• Premature discontinuation due to side effects - most adverse effects diminish over time 4, 7
• Failure to adjust doses in patients with renal impairment 2, 6
• Overlooking potential drug interactions, particularly with antidepressants 6
• Not addressing cardiovascular risk factors that may contribute to neuropathy 1