What is the therapeutic dose for gabapentin (Neurontin) in adults with neuropathic pain or epilepsy, considering factors such as renal impairment and age?

Gabapentin Therapeutic Dosing for Neuropathic Pain and Epilepsy

For neuropathic pain in adults, start gabapentin at 300 mg once daily or at bedtime on day 1, increase to 300 mg three times daily (900 mg/day) by day 3, then titrate upward by 300 mg every 3-7 days until reaching the target therapeutic dose of 1800-3600 mg/day in three divided doses. 1

Initial Dosing and Titration Protocol

• Start with 300 mg on day 1 (at bedtime or once daily), increase to 600 mg/day on day 2, then 900 mg/day (300 mg three times daily) by day 3 1, 2
• Titrate by 300 mg increments every 3-7 days as tolerated until reaching therapeutic effect or maximum dose 1
• Three-times-daily dosing is mandatory due to gabapentin's saturable, nonlinear absorption pharmacokinetics—once or twice daily dosing is ineffective 1

Critical Pharmacokinetic Consideration

Gabapentin has dose-dependent bioavailability that decreases as dose increases: 60% at 900 mg/day, 47% at 1200 mg/day, 34% at 2400 mg/day, and only 27% at 4800 mg/day 3. This saturable absorption necessitates divided dosing throughout the day to maximize drug exposure 1.

Target Therapeutic Dose Range

• Minimum effective dose: 1800 mg/day (600 mg three times daily) for most neuropathic pain conditions 1
• Standard therapeutic range: 1800-3600 mg/day in three divided doses 1, 4, 5
• Maximum dose: 3600 mg/day (1200 mg three times daily), though some patients may require this higher end 1, 2

Evidence for Efficacy

In postherpetic neuralgia, 32% of patients achieve at least 50% pain relief with gabapentin 1200 mg/day or greater versus 17% with placebo (NNT 6.7) 5. In painful diabetic neuropathy, 38% achieve substantial benefit versus 21% with placebo (NNT 5.9) 5.

Duration of Adequate Trial

• Minimum trial duration: 3-8 weeks for titration plus 2 weeks at maximum tolerated dose 1
• Full therapeutic trial may require 2 months or more before declaring treatment failure, as efficacy develops gradually over several weeks 1, 4
• Pain relief is not immediate—patients must understand this requires gradual dose escalation and patience 1

Special Population Adjustments

Elderly or Medically Frail Patients

• Start at 100 mg at bedtime (lower than standard 300 mg) 1
• Slower titration with increases every 3-7 days or longer to reduce fall risk from dizziness 1
• Elderly patients have reduced apparent oral clearance (225 mL/min in those under 30 years versus 125 mL/min in those over 70 years) 3
• Effective dose may be lower than standard ranges (potentially 900-1800 mg/day) due to decreased renal function and increased sensitivity 4

Renal Impairment

• Mandatory dose reduction required based on creatinine clearance, as gabapentin is eliminated 95% unchanged by the kidneys 1, 3
• Gabapentin half-life increases from 5-7 hours in normal renal function to significantly longer in renal impairment 3
• Dose adjustments:
  • CrCl 30-60 mL/min: reduce total daily dose by approximately 50% 1
  • CrCl 15-30 mL/min: reduce by 75% 1
  • CrCl <15 mL/min: reduce by 85-90% 1
• Gabapentin can be removed by hemodialysis 3

Common Pitfalls to Avoid

• Do NOT use once-daily or twice-daily dosing for standard gabapentin—three times daily is essential due to saturable absorption 1
• Do NOT rush titration in elderly patients—this increases fall risk from dizziness and somnolence 1
• Do NOT discontinue abruptly—taper gradually over at least 1 week to avoid withdrawal symptoms 1
• Do NOT declare treatment failure prematurely—allow the full 2-month trial period as efficacy develops gradually 1
• Do NOT use standard doses in renal impairment—dose reduction is mandatory 1

Adverse Effects Profile

• Most common side effects: dizziness (19%), somnolence (14%), peripheral edema (7%), and gait disturbance (14%) 5
• These effects are typically mild to moderate and often transient, usually subsiding within approximately 10 days 1, 2
• Adverse event withdrawals occur in 11% of patients versus 8.2% with placebo (NNH 30) 5
• Gradual titration minimizes side effects 1, 4

Expected Outcomes

• About 3-4 out of 10 patients achieve at least 50% pain relief with gabapentin at therapeutic doses, compared to 1-2 out of 10 with placebo 5
• Over half of treated patients will not have worthwhile pain relief but may still experience adverse events 5
• This degree of pain relief (≥50% reduction) is associated with important beneficial effects on sleep interference, fatigue, depression, quality of life, function, and work 5

Condition-Specific Considerations

HIV-Associated Neuropathic Pain

• Typical regimen titrates to 2400 mg/day in divided doses over 4 weeks 1
• The Infectious Diseases Society of America strongly recommends gabapentin as first-line treatment (strong recommendation, moderate-quality evidence) 1

Unexplained Chronic Cough

• Start at 300 mg once daily, escalate to maximum tolerable dose of 1800 mg in two divided doses 1, 4

Neuropathic Corneal Pain

• Initiate at 600 mg once daily, increase every 3 days to 1800 mg divided in 3 doses (third-line agent per American Academy of Ophthalmology) 1