What medications are used to treat neuropathy?

Medications for Neuropathic Pain

First-line medications for neuropathic pain include tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors (SNRIs), and anticonvulsants (pregabalin and gabapentin), with duloxetine and pregabalin being the only FDA-approved medications specifically for diabetic peripheral neuropathy. 1

First-Line Medications

Anticonvulsants

• Pregabalin (300-600 mg/day)

  • FDA-approved for diabetic peripheral neuropathy, postherpetic neuralgia, and neuropathic pain associated with spinal cord injury 2
  • Number needed to treat (NNT) of 4.04 for 600 mg/day and 5.99 for 300 mg/day 1
  • Dosing: Start at 50 mg three times daily or 75 mg twice daily, increase to 300 mg/day after 3-7 days, then by 150 mg/day every 3-7 days as tolerated 1
  • Side effects: Dizziness, somnolence, peripheral edema, headache, weight gain 1

• Gabapentin (900-3600 mg/day)

  • Well-established for painful diabetic neuropathy 1
  • Dosing: Start at 100-300 mg at bedtime or 100-300 mg three times daily, increase by 100-300 mg every 1-7 days as tolerated 1
  • Side effects: Similar to pregabalin - dizziness, somnolence, peripheral edema 3
  • Provides good pain relief in postherpetic neuralgia and diabetic neuropathy with 3-4 out of 10 patients achieving at least 50% pain reduction 3

Tricyclic Antidepressants (TCAs)

• Amitriptyline or Imipramine (25-75 mg/day)
  • NNT of 1.5-3.5 when carefully titrated 1
  • Dosing: Start at 10 mg/day (especially in older patients), increase as needed to 75 mg/day 1
  • Side effects: Drowsiness, anticholinergic effects, risk of cardiac events at doses >100 mg/day 1
  • Caution: Obtain ECG for patients >40 years or with cardiac history; avoid if PR or QTc interval prolongation 1

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

• Duloxetine (60-120 mg/day)

  • FDA-approved for diabetic peripheral neuropathy 1
  • NNT of 4.9 for 120 mg/day and 5.2 for 60 mg/day 1
  • Dosing: Start at 30 mg once daily, increase to 60 mg once daily after 1 week 1
  • Side effects: Nausea, somnolence, dizziness, constipation, dry mouth, reduced appetite 1
  • Advantage: Has antidepressant effects in addition to analgesic effects 1

• Venlafaxine (150-225 mg/day)

  • Effective for painful neuropathy 1
  • Dosing: Start at 37.5 mg once or twice daily, increase by 75 mg each week 1
  • Caution: Cardiovascular adverse events limit use in diabetes 1

Second-Line Medications

Topical Agents

• Lidocaine 5% patch
  • Most appropriate for well-localized neuropathic pain 1
  • Excellent tolerability with minimal systemic absorption 1
  • Not likely beneficial in central neuropathic pain 1

Opioids and Related Medications

• Tramadol (200-400 mg/day)

  • NNT of 4.7 for neuropathic pain 1
  • Weak opioid μ-receptor agonist that also inhibits reuptake of serotonin and norepinephrine 1
  • Caution: Risk of serotonin syndrome when combined with SSRIs/SNRIs 1

• Strong opioids (smallest effective dose)

  • Should not be first-line for long-term management of chronic neuropathic pain 1
  • Consider only after failure of first-line therapies for moderate to severe pain 1
  • When appropriate, combination of morphine and gabapentin may be considered for additive effects 1

Special Considerations

Chemotherapy-Induced Peripheral Neuropathy

• Duloxetine shows moderate clinical benefit, especially for platinum-based therapies 1
• Venlafaxine can be considered (small randomized trial) 1

HIV-Associated Neuropathic Pain

• Alpha lipoic acid recommended 1
• Avoid lamotrigine 1

Treatment Algorithm

1. Initial Assessment:

   • Determine type of neuropathy (diabetic, postherpetic, HIV-associated, etc.)
   • Assess pain severity, functional impact, and comorbidities

2. First-Line Treatment:

   • For most neuropathic pain:
     • Start with either pregabalin/gabapentin OR duloxetine/TCA based on:
       • Patient comorbidities (avoid TCAs in cardiac disease)
       • Side effect profile concerns
       • Specific neuropathy type (duloxetine preferred for chemotherapy-induced)

3. Titration and Monitoring:

   • Pregabalin: Start 50-75 mg BID, titrate to 300-600 mg/day
   • Gabapentin: Start 100-300 mg daily, titrate to 900-3600 mg/day
   • Duloxetine: Start 30 mg daily, titrate to 60-120 mg/day
   • TCAs: Start 10-25 mg at bedtime, titrate to 75 mg/day (not exceeding 100 mg)
   • Monitor for side effects and efficacy over 4-8 weeks

4. If Inadequate Response:

   • Try alternative first-line agent from different class
   • Consider combination therapy (e.g., anticonvulsant + SNRI)
   • For localized pain, add topical lidocaine

5. For Refractory Pain:

   • Consider tramadol or time-limited trial of opioids
   • Refer to pain specialist for complex cases

Common Pitfalls to Avoid

1. Underdosing: Clinical practice often uses lower doses than those proven effective in trials (especially with gabapentin) 4

2. Inadequate trial duration: Allow 4-8 weeks at therapeutic doses before determining failure 1

3. Ignoring cardiac risk with TCAs: Avoid doses >100 mg/day, especially in patients with cardiovascular disease 1

4. Overlooking renal function: Both pregabalin and gabapentin require dose adjustment in renal impairment 5

5. Expecting complete pain relief: Set realistic expectations - most patients achieve partial relief (30-50% reduction) 3