What is the next step in evaluating and managing a patient with bilateral leg pain and cramping unresponsive to gabapentin (Neurontin)?

Evaluation and Management of Bilateral Leg Pain and Cramping Unresponsive to Gabapentin

The next step in evaluating a patient with bilateral leg pain and cramping unresponsive to gabapentin should include laboratory testing for peripheral arterial disease and consideration of alternative neuropathic pain medications such as pregabalin or duloxetine. 1, 2

Initial Laboratory Workup

For a patient with bilateral leg pain and cramping not responding to gabapentin, the following laboratory tests should be ordered:

• Vascular assessment:

  • Ankle-brachial index (ABI) to evaluate for peripheral arterial disease 2
  • Doppler ultrasound of lower extremities if ABI is abnormal

• Neuropathy evaluation:

  • HbA1c to assess for diabetes
  • Vitamin B12 levels
  • Thyroid stimulating hormone (TSH)
  • Vitamin B6 levels
  • Folate levels
  • Serum protein electrophoresis and immunofixation
  • Creatine phosphokinase (CPK) 2

• Additional testing based on clinical suspicion:

  • Antinuclear antibody (ANA)
  • Erythrocyte sedimentation rate (ESR)
  • C-reactive protein (CRP)
  • Anti-neutrophil cytoplasmic antibodies (ANCA)
  • Anti-smooth muscle antibodies
  • SSA/SSB antibodies
  • RNP antibodies
  • Anti-dsDNA antibodies
  • Ganglioside antibodies
  • Anti-MAG antibodies
  • Anti-Hu (ANNA-1) antibodies
  • Thiamine levels
  • Testing for Lyme disease, hepatitis B/C, and HIV 2

Imaging Studies to Consider

• MRI of the spine (with contrast) if radiculopathy is suspected 2
• MRI of the brain if cranial nerve involvement is present
• MRI of the plexus if plexopathy is suspected 2

Alternative Pharmacological Management

Since gabapentin has failed to provide relief, consider the following alternatives:

1. Pregabalin (first alternative):

   • Starting dose: 75mg twice daily
   • Target dose: 150-600mg/day in divided doses
   • May have fewer cognitive side effects than gabapentin 1

2. Serotonin-norepinephrine reuptake inhibitors (SNRIs):

   • Duloxetine: 30mg daily initially, increasing to 60mg daily
   • Consider if pregabalin is not effective 2

3. Tricyclic antidepressants:

   • Amitriptyline: 10-25mg at bedtime, gradually increasing to 50-100mg
   • Use with caution in elderly patients due to anticholinergic effects 2, 1

4. Topical treatments:

   • Capsaicin 8% patch applied to painful areas
   • Consider 4% lidocaine application 60 minutes before capsaicin to reduce application discomfort 2

5. Alpha lipoic acid (ALA):

   • 600mg daily
   • Particularly beneficial for diabetic neuropathy 2, 1

Non-Pharmacological Interventions

1. Physical therapy:

   • Focus on core strengthening, flexibility, and proper body mechanics 1
   • Supervised exercise program to improve walking capacity

2. Cognitive behavioral therapy (CBT):

   • Promotes patient acceptance of responsibility for change
   • Addresses maladaptive behaviors related to pain 2

3. Consider referral to neurology:

   • Especially if symptoms persist or worsen despite intervention 2

Important Considerations and Pitfalls

• Gabapentin dosing issues: Ensure the patient was on an adequate dose (typically up to 2400mg/day in divided doses) before declaring treatment failure 2

• Gabapentin adverse effects: Be aware that high doses of gabapentin can cause myokymia, muscle spasms, and lower extremity edema which might be confused with worsening symptoms 3, 4

• Differential diagnosis: Consider alternative causes of bilateral leg pain:

  • Peripheral arterial disease
  • Spinal stenosis
  • Venous claudication
  • Chronic compartment syndrome
  • Hip or foot/ankle arthritis 2

• Medication trial duration: Allow adequate trial periods (4-6 weeks) for each new medication intervention 1

• Combination therapy: Consider combination therapy with medications having different mechanisms (e.g., pregabalin and duloxetine) for refractory cases 1

• Avoid: Lamotrigine is not recommended for neuropathic pain 2

By following this structured approach to evaluation and management, you can identify the underlying cause of the bilateral leg pain and provide effective alternative treatments for patients who have not responded to gabapentin.