What is the difference between pregabalin (lyrica) and gabapentin (neurontin)?

Pregabalin vs Gabapentin: Key Differences

Pregabalin offers superior and faster pain relief with more predictable dosing compared to gabapentin, though both medications share similar mechanisms of action and side effect profiles. 1

Pharmacokinetic Differences

The most clinically significant difference lies in their absorption characteristics:

• Pregabalin has linear, first-order absorption with >90% bioavailability regardless of dose, making dosing straightforward and predictable 2, 3, 4
• Gabapentin has nonlinear, saturable absorption with bioavailability dropping from 60% at 900 mg/day to only 33% at 3600 mg/day, making dose titration less predictable 3, 5, 4
• Pregabalin reaches maximum plasma concentrations within 1 hour versus 3-4 hours for gabapentin 4
• Both drugs have similar elimination half-lives of approximately 6 hours and are excreted renally unchanged 4

Dosing Differences

Maximum daily doses differ substantially:

• Pregabalin maximum: 600 mg/day in 2-3 divided doses 2
• Gabapentin maximum: 3600 mg/day in 3 divided doses (three-times-daily dosing is essential due to saturable absorption) 3, 5

Starting doses:

• Pregabalin: 75 mg twice daily or 50 mg three times daily (150 mg/day total) 2
• Gabapentin: 100-300 mg at bedtime or 100-300 mg three times daily 3, 5

Target therapeutic doses:

• Pregabalin: 300 mg/day provides optimal benefit-to-risk ratio for most patients 2
• Gabapentin: 1800-3600 mg/day in three divided doses 5

Clinical Efficacy Differences

Pregabalin demonstrates faster onset and superior efficacy:

• Pain relief with pregabalin occurs within 1.5-3.5 days versus over 4 weeks with placebo 2
• Pregabalin showed superior VAS pain scores at all time intervals up to 12-14 weeks (SMD -0.47,95% CI -0.74 to -0.19) 1
• Patients on pregabalin experienced more days with no/mild pain (MD 9.00,95% CI 8.93-9.07) and fewer days with severe pain (MD -3.00,95% CI -4.96 to -1.04) 1
• Pregabalin resulted in 50% lower opioid consumption (OR 0.50,95% CI 0.33-0.76) 1
• Gabapentin requires 2+ months for adequate trial (3-8 weeks titration plus 2 weeks at maximum tolerated dose) 5

Side Effect Profile

Both medications share nearly identical adverse effect profiles:

• Primary side effects include dizziness (23-46%), somnolence (15-25%), peripheral edema (10%), dry mouth, and constipation 2, 3
• Gabapentin has higher incidence of nausea and vomiting 1
• Both cause dose-dependent sedation, dizziness, and visual disturbances at comparable rates 2
• Elderly patients are more susceptible to falls, confusion, and sedation with both medications 2
• Both can cause weight gain and peripheral edema, particularly in elderly patients 2

Special Population Considerations

Renal impairment requires mandatory dose reduction for both medications:

• Pregabalin: Reduce total daily dose by approximately 50% for CrCl 30-60 mL/min, 75% for CrCl 15-30 mL/min, and 85-90% for CrCl <15 mL/min 2
• Gabapentin: Dose adjustment based on creatinine clearance values 5

Elderly patients:

• Both medications require lower starting doses and slower titration due to increased risk of dizziness, somnolence, confusion, and falls 2, 3, 5

Guideline Recommendations

First-line treatment hierarchy:

• Gabapentin is strongly recommended as first-line oral pharmacological treatment for chronic neuropathic pain, including HIV-associated neuropathic pain 3
• Pregabalin should be considered only after inadequate response to gabapentin (weak recommendation) 3
• For diabetic neuropathy, pregabalin has FDA approval but this does not establish it as superior to gabapentin for first-line use 3

Switching Between Medications

When transitioning from gabapentin to pregabalin:

• Start pregabalin 75 mg twice daily while continuing morning dose of gabapentin for at least the first few days 2
• Gradually taper gabapentin over several days to weeks to avoid withdrawal symptoms 2
• Neither medication should be abruptly discontinued 3

Critical Clinical Pitfalls to Avoid

Common dosing errors:

• Do not use once-daily or twice-daily dosing for standard gabapentin—three times daily administration is essential 5
• Do not routinely prescribe pregabalin 600 mg/day as standard dose; 300 mg/day provides optimal benefit-to-risk ratio for most patients 2
• Do not rush titration in elderly patients, as this increases fall risk from dizziness 5
• Allow full 2-month trial period for gabapentin before declaring treatment failure 5

Drug interactions:

• Both medications have serious breathing problems when combined with opioid pain medications, benzodiazepines, or other CNS depressants 2
• Neither drug is metabolized by nor inhibits hepatic enzymes, resulting in minimal drug-drug interactions 4