Gabapentin vs Pregabalin for Nerve Pain: Treatment Selection
For most patients with neuropathic pain, pregabalin is the preferred initial choice over gabapentin due to its superior pharmacokinetics, faster onset of action, and more predictable dosing, particularly when renal function is impaired. 1, 2
Key Pharmacokinetic Advantages of Pregabalin
Pregabalin demonstrates linear, predictable absorption with 90% bioavailability regardless of dose, while gabapentin has saturable, nonlinear absorption that drops from 60% to 33% bioavailability as doses increase from 900 to 3600 mg/day. 2
- Pregabalin reaches maximum plasma concentrations within 1 hour versus 3-4 hours for gabapentin 2
- Pregabalin provides pain relief within 1.5-3.5 days compared to gabapentin requiring 2+ months for adequate trial 1
- Pregabalin's linear pharmacokinetics make dose titration straightforward and predictable 1, 2
Critical Dosing Protocols
Pregabalin Initiation (Preferred)
- Start at 75 mg twice daily or 50 mg three times daily (150 mg/day total) 1, 3
- Increase to target dose of 300 mg/day within 1 week (150 mg twice daily or 100 mg three times daily) 1, 3
- Allow minimum 2-4 weeks at 300 mg/day before considering dose escalation 1
- Maximum dose 600 mg/day reserved only for patients with inadequate response at 300 mg/day who tolerate medication well 1, 3
Gabapentin Alternative Protocol
- Start at 100-300 mg at bedtime on day 1, increase to 300 mg three times daily by day 3 4, 5
- Titrate by 300 mg every 3-7 days to target dose of 1800-3600 mg/day in three divided doses 4, 5
- Requires 3-8 weeks for titration plus 2 weeks at maximum dose—potentially 2+ months total for adequate trial 4, 5
Efficacy Comparison
Postherpetic Neuralgia
- Pregabalin 300 mg/day: 50% achieve ≥30% pain reduction (NNT 3.9), 32% achieve ≥50% pain reduction (NNT 5.3) 6
- Gabapentin 1800-3600 mg/day: 32% achieve ≥50% pain reduction (NNT 6.7) 7
Painful Diabetic Neuropathy
- Pregabalin 300 mg/day: 47% achieve ≥30% pain reduction (NNT 22), 31% achieve ≥50% pain reduction 6
- Gabapentin 1800-3600 mg/day: 38% achieve ≥50% pain reduction (NNT 5.9) 7
Adverse Effect Profiles (Nearly Identical)
Both medications cause identical adverse effects at similar rates, with dizziness, somnolence, and peripheral edema being most common. 1
Common Side Effects
- Dizziness: Pregabalin 23-46%, Gabapentin 19% 1, 7
- Somnolence: Pregabalin 15-25%, Gabapentin 14% 1, 7
- Peripheral edema: Pregabalin 10%, Gabapentin 7% 1, 7
- Adverse event withdrawals: Pregabalin and Gabapentin both approximately 11% 6, 7
Critical Renal Function Considerations
Both medications require mandatory dose reduction in renal impairment, as both are eliminated primarily by renal excretion. 4, 1, 3
Pregabalin Renal Dosing
- CrCl 30-60 mL/min: Reduce dose by approximately 50% 1
- CrCl 15-30 mL/min: Reduce dose by approximately 75% 1
- CrCl <15 mL/min: Reduce dose by approximately 85-90% 1
Gabapentin Renal Dosing
- Start at 100-200 mg once daily in severe renal impairment (CrCl 15-29 mL/min) 4
- Maximum dose 200-700 mg/day as single daily dose in severe renal impairment 4
- Slower titration with increases every 3-7 days or longer is mandatory in renal impairment 4
When to Choose Gabapentin Over Pregabalin
- Cost considerations when insurance does not cover pregabalin (gabapentin is typically less expensive)
- Patient previously failed pregabalin but never tried gabapentin (individual response varies; some respond to one but not the other) 5
- Specific conditions where gabapentin has stronger evidence (e.g., HIV-associated neuropathic pain has moderate evidence for gabapentin but pregabalin showed no benefit) 6, 7
Critical Pitfalls to Avoid
- Never combine gabapentin and pregabalin—they have identical mechanisms of action and create unacceptable additive sedative burden without established efficacy benefits 1
- Never start pregabalin at 600 mg/day routinely—300 mg/day provides optimal benefit-to-risk ratio for most patients 1
- Never fail to assess renal function before initiating either medication—this is non-negotiable 4, 1
- Never use once-daily or twice-daily dosing for standard gabapentin—three times daily administration is essential due to saturable absorption 5
- Never abruptly discontinue either medication—taper gradually over minimum of 1 week to avoid withdrawal symptoms 1, 5
Special Population Considerations
Elderly Patients
- Start with lower doses and implement slower titration for both medications due to increased risk of falls, confusion, and sedation 4, 1
- Elderly patients invariably have reduced renal function requiring dose adjustment 4