Which is more effective for neuropathic pain, pregabalin (lyrica) or gabapentin (neurontin)?

Pregabalin vs. Gabapentin for Neuropathic Pain

Pregabalin is superior to gabapentin for neuropathic pain treatment, demonstrating better efficacy, faster onset of action, and a more favorable pharmacokinetic profile. 1

Mechanism of Action and Pharmacokinetic Differences

• Both medications bind to voltage-gated calcium channels at the α2δ subunit, inhibiting neurotransmitter release to reduce neuropathic pain 2
• Pregabalin has linear pharmacokinetics with predictable dose-response relationship, while gabapentin has nonlinear (saturable) absorption 2, 3
• Pregabalin has higher bioavailability (≥90% regardless of dose) compared to gabapentin (60% decreasing to 33% as dosage increases from 900 to 3600 mg/day) 3
• Pregabalin reaches peak plasma concentration faster (within 1 hour) compared to gabapentin (3-4 hours) 3

Comparative Efficacy

• Recent meta-analysis (2024) shows pregabalin is superior to gabapentin on the Visual Analog Scale (VAS) for pain reduction at various time intervals up to 12-14 weeks 1
• Patients on pregabalin experience more days with no/mild pain and fewer days with severe pain compared to gabapentin 1
• Pregabalin leads to greater improvements in quality of life measures (SF-12/SF-36/EQ-5D scores) 1
• Pregabalin results in lower opioid consumption (OR 0.50,95% CI 0.33-0.76) 1

Dosing Considerations

• Pregabalin: Start at 50 mg three times daily or 75 mg twice daily, with 150 mg/day being efficacious in some trials; doses >300 mg/day are not consistently more effective and have more side effects 2
• Gabapentin: Start at 100-300 mg at bedtime or 100-300 mg three times daily, with maximum dose of 3600 mg/day in 3 divided doses 2, 4
• For neuropathic pain, pregabalin at 450 mg/day appears comparable to the maximum effect of gabapentin 3

Side Effect Profile

• Both medications can cause dizziness, somnolence, dry mouth, and constipation 5, 2
• Gabapentin has a higher incidence of nausea and vomiting compared to pregabalin 1
• Pregabalin demonstrates a better overall adverse event profile 2, 1
• Both medications require dose adjustment in renal impairment and should be tapered gradually to avoid withdrawal symptoms 2

Special Considerations

• In elderly patients or those with cardiovascular disease, start with lower doses and titrate slowly 5, 2
• Cost may be a factor in medication selection, with generic gabapentin typically being less expensive than pregabalin 2
• For patients with refractory neuropathic pain who have failed other treatments (including gabapentin), pregabalin has shown benefit 6

Clinical Algorithm for Selection

1. For most patients with neuropathic pain, start with pregabalin due to superior efficacy, more predictable pharmacokinetics, and better side effect profile 1
2. Consider gabapentin as an alternative if:
   • Cost is a major concern 2
   • Patient has previously tolerated gabapentin well 7
3. For either medication:
   • Start at lower doses and titrate gradually to minimize side effects 2
   • Monitor for efficacy and adjust dose accordingly 2
   • Ensure adequate trial duration (at least 2-4 weeks at therapeutic dose) 7

Both medications are considered third-line agents for neuropathic pain according to ophthalmology guidelines, but their efficacy is well-established for conditions like diabetic neuropathy and postherpetic neuralgia 5.