What is the maximal dose of gabapentin (Neurontin)?

From the Guidelines

The maximum recommended dose of gabapentin for adults is 3,600 mg per day, typically divided into three equal doses of 1,200 mg each. This dose is based on the study by 1, which provides guidelines for the pharmacological management of neuropathic pain. According to the study, the maximum dosage of gabapentin is 3,600 mg/d in 3 divided doses, and an adequate trial of treatment with gabapentin can require 2 months or more.

Key Considerations

• The dose should be individualized based on efficacy and tolerability rather than automatically targeting the maximum dose.
• Patients should start at a lower dose (often 100-300 mg on day 1) and gradually titrate upward based on response and tolerability, as recommended by 1.
• Dose adjustments are necessary for patients with renal impairment, with reduced maximum doses based on creatinine clearance.
• Common side effects at higher doses include dizziness, somnolence, peripheral edema, and gait disturbances.

Titration and Dosage

• The study by 1 suggests that increases in dose should be made until pain relief, dose-limiting adverse effects, or 3600 mg/d in 3 divided doses is reached.
• 1 recommends dose increments of 50%-100% every few days, with slower titration for the elderly or medically frail.
• The therapeutic effect of gabapentin relates to its binding to the α2δ subunit of voltage-gated calcium channels, which reduces the release of excitatory neurotransmitters.

Special Populations

• Patients with renal insufficiency require dose adjustment, as recommended by 1 and 1.
• The elderly or medically frail may require slower titration, as recommended by 1.

From the FDA Drug Label

In clinical studies, efficacy was demonstrated over a range of doses from 1800 mg/day to 3600 mg/day with comparable effects across the dose range; however, in these clinical studies, the additional benefit of using doses greater than 1800 mg/day was not demonstrated. Dosages up to 2400 mg/day have been well tolerated in long-term clinical studies Doses of 3600 mg/day have also been administered to a small number of patients for a relatively short duration, and have been well tolerated.

The maximal dose of gabapentin is 3600 mg/day 2.

From the Research

Maximal Dose Gabapentin

• The maximal dose of gabapentin is not explicitly stated in the provided studies, but the effective dose for treating postherpetic neuralgia (PHN) is mentioned as ≥ 1,800 mg/day 3.
• In a retrospective evaluation of gabapentin and pregabalin use in patients with PHN, it was found that only 14% of patients treated with gabapentin reached the target dosage of 1,800 mg/day 3.
• Another study found that among patients prescribed gabapentin, few received a prescription for a therapeutic dose, whereas a greater proportion of patients prescribed pregabalin received a prescription for a therapeutic dose 4.
• The studies suggest that gabapentin is often not used at optimal doses, which may be associated with supplementary use of other analgesics, especially opioids 3, 4.

Comparison with Pregabalin

• Pregabalin has been shown to be effective in treating PHN at doses of 150-600 mg/day, with significant improvements in pain scores and sleep interference 5.
• A study comparing duloxetine supplemented with pregabalin and amitriptyline supplemented with pregabalin found that both combinations were effective in treating PHN, with no significant difference in pain relief between the two groups 6.
• Another study found that pregabalin was more effective than gabapentin in treating PHN, with significantly higher clinical effectiveness and shorter time to pain relief 7.

Adverse Events

• The most common adverse events associated with gabapentin and pregabalin are dizziness, somnolence, and peripheral edema 5, 3.
• A study found that the overall incidence of adverse events was equivalent between gabapentin and pregabalin, but pregabalin was associated with significantly lower scores for sleep quality and negative emotions 7.