Key Differences Between Gabapentin and Pregabalin
Pregabalin offers more predictable pharmacokinetics with linear absorption and requires lower total daily doses (maximum 600 mg/day vs 3600 mg/day for gabapentin), making it easier to dose, though gabapentin is typically less expensive and both medications have similar efficacy and side effect profiles for neuropathic pain. 1, 2
Pharmacokinetic Differences
The most clinically significant difference lies in how these medications are absorbed:
- Gabapentin has saturable, nonlinear absorption that decreases as doses increase—bioavailability drops from 60% at 900 mg/day to only 33% at 3600 mg/day, with peak concentrations reached in 3-4 hours 3
- Pregabalin has linear, predictable absorption maintaining ≥90% bioavailability regardless of dose, with peak concentrations achieved within 1 hour 3
- This means pregabalin plasma concentrations increase proportionally with dose increases, while gabapentin does not 1, 3
Dosing Differences
Maximum daily doses differ substantially:
Starting doses:
- Gabapentin: 100-300 mg at bedtime or three times daily 1
- Pregabalin: 50 mg three times daily or 75 mg twice daily 1, 2
The equianalgesic relationship suggests 30 mg of mirogabalin equals 600 mg pregabalin and over 1200 mg gabapentin, indicating pregabalin requires roughly half the dose of gabapentin for similar effects 4
Shared Characteristics
Both medications work identically by binding to voltage-gated calcium channels at the α2δ subunit, inhibiting excitatory neurotransmitter release 5, 1
Common side effects for both include:
- Dose-dependent dizziness and somnolence 1, 2
- Dry mouth and constipation 1, 2
- Weight gain and peripheral edema, particularly in elderly patients 1, 2, 6
Both medications:
- Are eliminated unchanged renally with ~6 hour half-lives, requiring dose adjustment in renal impairment 6, 3
- Do not bind to plasma proteins 3
- Are not metabolized by hepatic enzymes and have minimal drug-drug interactions 6, 3
- Should never be discontinued abruptly—taper gradually to avoid withdrawal 1
Clinical Efficacy
For neuropathic pain, pregabalin 450 mg/day appears to reduce pain comparably to the predicted maximum effect of gabapentin 3. However, higher pregabalin doses above 300 mg/day are not consistently more effective and increase adverse effects 1. Both are considered first-line anticonvulsants for neuropathic pain (except trigeminal neuralgia) 5.
Practical Considerations
Cost typically favors gabapentin, as generic formulations are less expensive than pregabalin 1
Pregabalin may be better tolerated overall due to its superior adverse event profile compared to alternatives like amitriptyline 1
For elderly or medically frail patients, both require lower starting doses and slower titration (dose increments of 50-100% every few days) 1, 2
Critical Pitfall
Never prescribe gabapentin and pregabalin together—this represents therapeutic duplication that can cause severe drowsiness, dizziness, fatigue, and ataxia without additional benefit 7. While some sources mention potential synergistic effects 8, the risk of adverse effects from combining these mechanistically identical medications outweighs theoretical benefits in routine practice 7.