What is the recommended gabapentin dosing regimen for an adult with neuropathic pain and no contraindications?

Gabapentin Dosing for Neuropathic Pain

Start gabapentin at 300 mg on day 1, increase to 600 mg/day (300 mg twice daily) on day 2, then 900 mg/day (300 mg three times daily) on day 3, and titrate upward by 300 mg every 3–7 days to reach the target therapeutic range of 1800–3600 mg/day in three divided doses. 1

Standard Titration Protocol

• Initiate with 300 mg once daily (or at bedtime) on day 1, escalate to 600 mg/day divided twice daily on day 2, then advance to 900 mg/day divided three times daily on day 3. 1
• After reaching 900 mg/day, increase by 300 mg increments every 3–7 days as tolerated until the therapeutic dose is achieved. 2, 1
• The FDA-approved titration schedule provides the foundation for adult dosing in neuropathic pain conditions. 1

Target Therapeutic Dose Range

• The minimum effective dose is 1800 mg/day (600 mg three times daily), which represents the threshold for clinically meaningful pain relief in most neuropathic pain conditions. 2, 1, 3
• The maximum recommended dose is 3600 mg/day (1200 mg three times daily), though additional benefit above 1800 mg/day has not been consistently demonstrated in clinical trials. 2, 1
• For postherpetic neuralgia, 32% of patients achieve at least 50% pain reduction at doses of 1800–3600 mg/day versus 17% with placebo (NNT 6.7). 2, 4
• For painful diabetic neuropathy, 38% of patients achieve at least 50% pain reduction at doses of 1800–3600 mg/day versus 21% with placebo (NNT 5.9). 2, 4

Mandatory Three-Times-Daily Dosing

• Gabapentin must be administered three times daily because of its nonlinear, saturable absorption pharmacokinetics; the drug's bioavailability decreases as dose size increases. 2
• The maximum interval between doses must not exceed 12 hours to maintain therapeutic plasma levels. 1
• Once-daily or twice-daily regimens lead to subtherapeutic drug levels and treatment failure. 2

Duration of Adequate Trial

• Allow 3–8 weeks for titration plus an additional 2 weeks at the maximum tolerated dose before declaring treatment failure. 2, 5
• An adequate therapeutic trial typically requires approximately 2 months because gabapentin's analgesic effect develops gradually over several weeks. 2
• Do not prematurely discontinue therapy; efficacy may take several weeks to manifest even at therapeutic doses. 2

Elderly Patient Considerations

• Start at 100–200 mg/day in geriatric patients and use slower titration increments (every 3–7 days or longer) to minimize adverse effects. 2, 5
• Elderly patients experience higher rates of adverse effects: dizziness (19%), somnolence (14%), peripheral edema (7%), and gait disturbance (9%). 2
• The effective dose in older adults may be lower than the standard adult range due to age-related pharmacokinetic changes and decreased renal function. 2
• Rapid titration in elderly patients increases fall risk from dizziness; slower dose escalation is mandatory. 2

Renal Impairment Dose Adjustments

Dose reduction is mandatory based on creatinine clearance (CrCl) because gabapentin is eliminated primarily by renal excretion. 2, 1

Creatinine Clearance	Total Daily Dose	Dosing Frequency
≥ 60 mL/min	900–3600 mg	Three times daily
30–59 mL/min	400–1400 mg	Twice daily
15–29 mL/min	200–700 mg	Once daily
< 15 mL/min	100–300 mg	Once daily

• Calculate CrCl using the Cockcroft-Gault equation before initiating therapy. 2, 1
• For patients on hemodialysis, administer maintenance doses based on CrCl plus a supplemental post-hemodialysis dose (125–350 mg) after each 4-hour dialysis session. 1

Common Adverse Effects

• Dizziness (19%), somnolence (14%), peripheral edema (7%), and gait disturbance (9%) are the most common adverse effects. 2, 4
• Most adverse effects are mild to moderate and typically transient, occurring predominantly during the titration phase. 3, 6
• Adverse event withdrawals occur in 11% of patients on gabapentin versus 8.2% on placebo (NNH 30). 4
• Serious adverse events (3.2%) are no more common than placebo (2.8%). 4

Combination Therapy Options

• Gabapentin may be used as a coanalgesic with opioids, tricyclic antidepressants (e.g., nortriptyline), or topical agents to enhance overall pain control. 2, 5
• Adding nortriptyline to gabapentin provides superior pain relief compared with either agent alone. 2
• Co-administration with low-dose opioids allows better analgesia while permitting lower opioid dosing. 2

Critical Pitfalls to Avoid

• Do not use once-daily or twice-daily dosing schedules for immediate-release gabapentin; three-times-daily administration is essential due to saturable absorption. 2
• Do not rush titration in elderly patients; slower increments reduce fall risk from dizziness-related adverse effects. 2
• Do not discontinue abruptly; taper gradually over at least 1 week to avoid withdrawal symptoms. 2
• Do not declare treatment failure before completing the full 2-month trial at therapeutic doses, as efficacy develops gradually. 2

Expected Outcomes

• Approximately 35% of patients achieve at least 50% pain reduction with gabapentin at therapeutic doses, compared with 21% on placebo. 4, 7
• Over half of patients treated with gabapentin will not achieve worthwhile pain relief but may still experience adverse events. 4
• Pain relief is associated with beneficial effects on sleep interference, fatigue, depression, quality of life, function, and work capacity. 4, 7