What are the alternatives to gabapentin (Neurontin) for treating neuropathic pain?

Alternatives to Gabapentin for Neuropathic Pain

Pregabalin is the preferred alternative to gabapentin for treating neuropathic pain, with a starting dose of 75 mg twice daily and a target dose of 300-600 mg/day in divided doses. 1

First-Line Alternatives

Pregabalin

• Dosing: Start at 75 mg twice daily, titrate to 300-600 mg/day in divided doses
• Advantages over gabapentin:
  • More efficiently absorbed through GI tract 2
  • More predictable and linear pharmacokinetics 3
  • May require fewer daily doses
• Renal adjustment required:

  Creatinine Clearance (mL/min)	Total Daily Dose Range (mg/day)
  ≥60	300-600
  30-59	150-300
  15-29	75-150
  <15	25-75

• FDA approved for neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, and spinal cord injury 4

Tricyclic Antidepressants

• Options: Nortriptyline or desipramine (secondary amines) preferred over amitriptyline or imipramine (tertiary amines)
• Dosing: Start with 10-25 mg nightly, increase to 50-150 mg nightly 2
• Advantages: Lower cost, once-daily dosing
• Limitations: Anticholinergic side effects (dry mouth, urinary hesitancy, sedation), contraindicated in patients with cardiovascular disease 1

Duloxetine (SNRI)

• Dosing: Start at 30 mg daily for one week, then increase to 60-120 mg daily 2, 1
• Advantages: Also treats depression if present, fewer anticholinergic effects than TCAs
• FDA approved for diabetic peripheral neuropathy 1

Second-Line Alternatives

Venlafaxine (SNRI)

• Dosing: Start at 50-75 mg daily, increase to 75-225 mg daily 2
• Considerations: May cause hypertension at higher doses

Topical Agents

• Lidocaine patch 5%: Apply daily to painful site with minimal systemic absorption 2
• Diclofenac gel/patch: Apply 3 times daily (gel) or once/twice daily (patch) 2
• Capsaicin 8%: Evidence of efficacy in HIV-associated neuropathic pain 2

Other Anticonvulsants

• Lamotrigine: Shown to reduce daily pain ratings and cold-induced pain in central post-stroke pain 2
• Carbamazepine/Phenytoin: May be considered as second-line treatments for central post-stroke pain 2

Treatment Algorithm

1. Start with pregabalin if no contraindications:

   • Begin at 75 mg twice daily
   • Titrate to 300-600 mg/day over 2-4 weeks
   • Assess response after 4 weeks at target dose

2. If inadequate response or intolerance to pregabalin:

   • Switch to tricyclic antidepressant (nortriptyline or desipramine) if no cardiovascular contraindications
   • OR switch to duloxetine if cardiovascular concerns exist

3. If still inadequate response:

   • Consider combination therapy (e.g., pregabalin + duloxetine)
   • Add topical agents for localized pain
   • Consider referral to pain specialist for more advanced options

Special Considerations

• Elderly patients: Start with lower doses and titrate more slowly 1
• Renal impairment: Dose adjustment required for both pregabalin and gabapentin 1, 4
• Common side effects to monitor:
  • Pregabalin/gabapentin: Dizziness, somnolence, peripheral edema, weight gain 4, 5
  • TCAs: Anticholinergic effects, sedation, cardiac conduction abnormalities
  • SNRIs: Nausea, dizziness, somnolence, hypertension

Common Pitfalls to Avoid

• Inadequate dosing: Many patients require higher doses for effective pain control
• Premature discontinuation: Therapeutic effects may take several weeks to develop
• Overlooking non-pharmacological approaches: Consider adding cognitive behavioral therapy, physical therapy, or TENS 1
• Failing to adjust doses in renal impairment: Both pregabalin and gabapentin require dose adjustment 1, 4

Remember that treatment of neuropathic pain often requires a trial-and-error approach, and patients should be informed that therapeutic effects typically begin after several days to weeks of treatment.