What is the recommended use and dosing of Gabapentin (Neurontin) for treating neuropathic pain and epilepsy?

Gabapentin for Neuropathic Pain and Epilepsy

Gabapentin is a first-line treatment for neuropathic pain at doses of 1800-3600 mg/day divided three times daily, with initiation at 300 mg on day 1,600 mg on day 2, and 900 mg on day 3, then titrating upward based on response. 1

Dosing for Neuropathic Pain

Initial Titration Schedule

• Day 1: 300 mg once daily 1
• Day 2: 300 mg twice daily (600 mg/day) 1
• Day 3: 300 mg three times daily (900 mg/day) 1
• Continue titrating upward to 1800 mg/day (600 mg three times daily) as the target therapeutic dose 1

Therapeutic Dose Range

• Target dose: 1800 mg/day provides effective pain relief for most patients with neuropathic pain 2, 1
• Maximum dose: 3600 mg/day may be needed in some patients, though additional benefit above 1800 mg/day has not been consistently demonstrated 1, 3
• Doses should be divided into three daily administrations with no more than 12 hours between doses 1

Evidence for Efficacy

Postherpetic Neuralgia:

• 32% of patients achieve substantial benefit (≥50% pain relief) with gabapentin ≥1200 mg/day versus 17% with placebo (NNT 6.7) 3
• 46% achieve moderate benefit (≥30% pain relief) versus 25% with placebo (NNT 4.8) 3

Diabetic Neuropathy:

• 38% achieve substantial benefit with gabapentin ≥1200 mg/day versus 21% with placebo (NNT 5.9) 3
• 52% achieve moderate benefit versus 37% with placebo (NNT 6.6) 3
• The Mayo Clinic Proceedings confirms gabapentin is well-established for painful diabetic peripheral neuropathy, though clinical practice doses are often lower than the 3600 mg/day used in trials 2

HIV-Associated Neuropathic Pain:

• The HIV Medicine Association of IDSA recommends gabapentin as first-line oral pharmacological treatment for chronic HIV-associated neuropathic pain 2
• Titrate to maximum 2400 mg/day over 4 weeks, which improves pain scores and sleep 2
• Note that 80% of patients experience somnolence at this dose 2

Dosing for Epilepsy

Adults and Adolescents ≥12 Years

• Starting dose: 300 mg three times daily 1
• Maintenance dose: 300-600 mg three times daily 1
• Maximum studied dose: 2400 mg/day is well-tolerated in long-term studies; 3600 mg/day has been administered short-term to small numbers of patients 1
• Administer three times daily with maximum 12-hour interval between doses 1

Pediatric Patients (3-11 Years)

• Starting dose: 10-15 mg/kg/day divided three times daily 1
• Maintenance dose (ages 3-4): 40 mg/kg/day divided three times daily 1
• Maintenance dose (ages 5-11): 25-35 mg/kg/day divided three times daily 1
• Titrate upward over approximately 3 days 1
• Doses up to 50 mg/kg/day have been well-tolerated 1

Special Populations

Renal Impairment

Dose adjustment is mandatory based on creatinine clearance: 1

• CrCl ≥60 mL/min: 900-3600 mg/day (300-1200 mg three times daily) 1
• CrCl 30-59 mL/min: 400-1400 mg/day (200-700 mg twice daily) 1
• CrCl 15-29 mL/min: 200-700 mg/day (200-700 mg once daily) 1
• CrCl <15 mL/min: 100-300 mg/day (100-300 mg once daily) 1
• Hemodialysis patients: Maintenance dose based on CrCl plus supplemental post-dialysis dose of 125-350 mg after each 4-hour session 1

Elderly Patients

• Use lower starting doses and slower titration due to age-related decline in renal function 2, 1
• Dose selection should be based on creatinine clearance values 1
• The Mayo Clinic Proceedings recommends considering lower starting dosages and cautious titration to reduce dose-dependent dizziness and sedation 2

Pharmacokinetic Considerations

Absorption Characteristics

• Gabapentin has nonlinear pharmacokinetics due to saturable absorption, requiring careful titration 2
• This contrasts with pregabalin, which has linear pharmacokinetics and more predictable dosing 2, 4
• An adequate trial requires 2 months or more due to the extended titration period needed 2

Mechanism of Action

• Gabapentin binds to the α-2-δ subunit of calcium channels, reducing calcium influx and neurotransmitter release in hyperexcited neurons 2
• It promptly elevates brain GABA levels within 1 hour of the first dose, offering rapid anticonvulsant effects 5

Adverse Effects

Common Side Effects

• Dizziness: 19% of patients 3
• Somnolence: 14% of patients 3
• Peripheral edema: 7% of patients 3
• Gait disturbance: 14% of patients 3
• These effects are dose-dependent and can be minimized with slower titration 2

Discontinuation Rates

• Adverse event withdrawals occur in 11% with gabapentin versus 8.2% with placebo (NNH 30) 3
• 63% experience at least one adverse event versus 49% with placebo (NNH 7.5) 3
• Serious adverse events are not significantly more common than placebo (3.2% vs 2.8%) 3

Discontinuation Protocol

Taper gabapentin gradually over a minimum of 1 week when discontinuing to avoid withdrawal symptoms 1. A longer taper period may be needed at the prescriber's discretion 1.

Clinical Pitfalls and Caveats

Limited Efficacy in Some Conditions

• In HIV-associated neuropathy specifically, a 2010 systematic review found gabapentin at 2400 mg/day showed no superiority over placebo in randomized controlled trials, with only topical capsaicin 8% and smoked cannabis showing efficacy 2
• This contrasts with the guideline recommendation for HIV neuropathy, highlighting the modest overall efficacy and high placebo response rates in neuropathic pain trials 2

Realistic Expectations

• Only 3-4 out of 10 patients achieve ≥50% pain relief with gabapentin compared to 1-2 out of 10 with placebo 3
• Over half of treated patients will not have worthwhile pain relief but may still experience adverse events 3

Drug Interactions

• Gabapentin has few drug interactions, which is an advantage over older anticonvulsants 2
• However, renal excretion requires careful attention to renal function and potential nephrotoxic medications 1