When to use pregabalin (Lyrica) versus gabapentin (Neurontin)?

Choosing Between Pregabalin and Gabapentin for Neuropathic Pain

Pregabalin is generally preferred over gabapentin for neuropathic pain due to its superior efficacy, faster onset of action, more predictable pharmacokinetics, and better side effect profile. 1

Pharmacokinetic Differences

• Pregabalin has linear pharmacokinetics with predictable dose-response relationship, while gabapentin has nonlinear (saturable) absorption, making dosing less predictable 2
• Pregabalin reaches maximum plasma concentration faster (within 1 hour) compared to gabapentin (3-4 hours) 2
• Pregabalin has higher and more consistent bioavailability (≥90%) regardless of dose, while gabapentin's bioavailability decreases from 60% to 33% as dosage increases 2
• Pregabalin requires shorter titration period (approximately 4 weeks) compared to gabapentin (approximately 2 months) 3

Clinical Indications for Pregabalin

• First choice for:

  • Fibromyalgia (FDA-approved) 4
  • Diabetic neuropathy (FDA-approved) 4
  • Postherpetic neuralgia (FDA-approved) 4
  • Neuropathic pain requiring rapid onset of action 3, 2
  • Patients with poor response to gabapentin 1

• Dosing: Start with 50-75 mg twice daily or 50 mg three times daily, gradually increasing to 300 mg/day after 3-7 days, then by 150 mg/day every 3-7 days as tolerated, with maximum dose of 600 mg/day 5

Clinical Indications for Gabapentin

• First choice for:

  • Restless legs syndrome (strong recommendation from AASM) 4
  • Postherpetic neuralgia (FDA-approved) 4
  • Patients with history of substance abuse (lower abuse potential than pregabalin) 6
  • Patients with cost concerns (generic gabapentin is typically less expensive) 6

• Dosing: Start with 100-300 mg at bedtime or 100-300 mg three times daily, with gradual titration to 900-3600 mg/day in divided doses 6

Comparative Efficacy

• Recent meta-analysis (2024) demonstrated that pregabalin has superior efficacy in alleviating neuropathic pain compared to gabapentin 1
• Pregabalin showed better results on Visual Analog Scale (VAS) at various time intervals up to 12-14 weeks 1
• Pregabalin led to significant improvements in quality of life scores and more days with no/mild pain 1
• Pregabalin resulted in lower opioid consumption compared to gabapentin 1

Side Effect Considerations

• Both medications have similar adverse effect profiles, primarily neuropsychological reactions (dizziness and drowsiness) 7
• Both can cause weight gain and peripheral edema, especially in elderly patients 7
• Gabapentin has higher incidence of nausea and vomiting compared to pregabalin 1
• Higher pregabalin doses (>300 mg/day) are not consistently more effective but have more adverse effects 5

Special Populations

• Elderly patients:

  • Both medications require lower starting doses and slower titration 6
  • Monitor for increased risk of dizziness, sedation, and falls 6

• Renal impairment:

  • Both medications require dosage reduction in patients with renal insufficiency 3, 5
  • Adjust dosages according to creatinine clearance 5

Conversion Between Medications

• When switching from pregabalin to gabapentin, use a 1:6 conversion ratio (1 mg pregabalin ≈ 6 mg gabapentin) 3
• For transitioning between medications, a gradual approach is recommended using 50% of original dose plus 50% of target dose for 4 days 3, 5
• Monitor for breakthrough pain during transitions, as gabapentin may take longer to reach full therapeutic effect 3

Common Pitfalls to Avoid

• Avoid starting at high doses without gradual titration, as this increases risk of adverse effects 6
• Avoid abrupt discontinuation of either medication in patients who have been on high doses for extended periods 3, 5
• Don't exceed maximum recommended doses (3600 mg/day for gabapentin, 600 mg/day for pregabalin) 6, 5
• Be aware that doses above 300 mg/day of pregabalin may not provide additional efficacy but increase side effects 5