What is the appropriate dosing and treatment protocol for a patient taking gabapentin (Neurontin) for neuropathic pain or epilepsy?

Gabapentin Dosing and Treatment Protocol

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, with subsequent titration by 300 mg every 3-7 days to reach the target therapeutic dose of 1800-3600 mg/day in three divided doses. 1

Initial Dosing Strategy

Start low and titrate gradually over the first week:

• Day 1: 300 mg once daily (at bedtime preferred) 1, 2
• Day 2: 600 mg/day (300 mg twice daily) 1
• Day 3: 900 mg/day (300 mg three times daily) 1

For elderly or medically frail patients, use slower titration starting at 100-300 mg at bedtime, with increases every 5-7 days rather than every 3 days to minimize fall risk from dizziness 2, 3.

Target Therapeutic Dose Range

The effective maintenance dose is 1800-3600 mg/day, administered in three divided doses (TID): 1, 2

• Minimum effective dose: 1800 mg/day (600 mg three times daily) 3, 4
• Maximum dose: 3600 mg/day (1200 mg three times daily) 1, 4
• Three times daily dosing is mandatory due to gabapentin's nonlinear, saturable absorption pharmacokinetics—once or twice daily dosing is ineffective 3, 2

Titration Schedule After Day 3

Increase by 300 mg increments every 3-7 days as tolerated until reaching 1800 mg/day, then continue titration to maximum 3600 mg/day if needed: 3, 2

• Week 1: Reach 900 mg/day (300 mg TID) 1
• Week 2: Increase to 1200-1500 mg/day (400-500 mg TID) 2
• Week 3: Increase to 1800 mg/day (600 mg TID) - minimum therapeutic dose 3
• Weeks 4-8: Continue titration by 300 mg every 3-7 days up to 3600 mg/day if inadequate response 3

Duration of Adequate Trial

Allow 3-8 weeks for titration PLUS 2 weeks at maximum tolerated dose before declaring treatment failure—an adequate trial may require 2 months or more: 2, 3

Efficacy develops gradually over several weeks, not immediately 2. In clinical trials, 32-38% of patients achieved at least 50% pain reduction with gabapentin 1800-3600 mg/day versus 17-21% with placebo 4.

Condition-Specific Dosing

Postherpetic Neuralgia

• Target dose: 1800 mg/day (600 mg TID) 1
• Maximum studied: 3600 mg/day, though additional benefit above 1800 mg/day was not consistently demonstrated 1
• NNT for 50% pain relief: 6.7 4

Painful Diabetic Neuropathy

• Target dose: 1800-3600 mg/day (600-1200 mg TID) 4, 5
• NNT for 50% pain relief: 5.9 4

HIV-Associated Neuropathic Pain

• Gabapentin is recommended as first-line oral pharmacological treatment 6
• Titrate to maximum 2400 mg/day over 4 weeks 6
• Note: Somnolence reported by 80% of patients at 2400 mg/day 6

Renal Dose Adjustment

Mandatory dose reduction required based on creatinine clearance: 1

CrCl (mL/min)	Total Daily Dose	Dosing Regimen
≥60	900-3600 mg/day	300-1200 mg TID
30-59	400-1400 mg/day	200-700 mg BID
15-29	200-700 mg/day	200-700 mg QD
<15	100-300 mg/day	100-300 mg QD
Hemodialysis	Maintenance dose based on CrCl + supplemental post-HD dose	125-350 mg after each 4-hour HD session

Adverse Effects and Management

Common adverse effects (dose-dependent): 4

• Dizziness: 19% of patients 4
• Somnolence: 14% of patients 4
• Peripheral edema: 7% of patients 4
• Gait disturbance: 14% of patients 4
• Ataxia and fatigue 7

These effects are typically mild to moderate and often subside within approximately 10 days from initiation 5. Gradual titration minimizes these side effects 2.

Adverse event withdrawals: 11% with gabapentin versus 8.2% with placebo (NNH 30) 4

Critical Pitfalls to Avoid

Do not rush titration in elderly patients—use every 5-7 day intervals to reduce fall risk from dizziness 3, 2

Do not use once or twice daily dosing—three times daily administration is essential due to saturable absorption 3

Do not discontinue abruptly—taper gradually over minimum of 1 week to avoid withdrawal symptoms 1, 3

Do not declare treatment failure prematurely—allow the full 2-month trial period as efficacy develops gradually 3, 2

Maximum time between doses should not exceed 12 hours 1

Administration Considerations

• Administer orally with or without food 1
• If dividing scored 600 mg or 800 mg tablets, take unused half-tablet as next dose within 28 days 1
• May be used as coanalgesic in combination with opioids, antidepressants, or topical agents 2

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: 4

• Postherpetic neuralgia: 32% substantial benefit (≥50% pain relief) versus 17% placebo 4
• Painful diabetic neuropathy: 38% substantial benefit versus 21% placebo 4
• Over half of treated patients will not have worthwhile pain relief but may experience adverse events 4