Michael J McLean1, Barry E Gidal. 1. Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee 37212, USA. michael.mclean@vanderbilt.edu
Abstract
BACKGROUND: Gabapentin is considered a safe and well-tolerated antipileptic drug (AED) with a favorable pharmacokinetic profile and a broad therapeutic index. However, recent studies have used higher doses and faster titration schedules than those used in the pivotal trials that established the efficacy of gabapentin in the treatment of partial seizures. OBJECTIVE: The purposes of this review were to assess the gabapentin titration and dosing regimens that have been published in peer-reviewed journals, to develop dosing recommendations to maximize antiseizure efficacy without compromising tolerability, and to formulate guidelines for an adequate therapeutic assessment of gabapentin dosage efficacy. METHODS: In the absence of sufficient placebo-controlled, double-blind studies, a formal evidence-based assessment could not be performed. However, a MEDLINE search using the search terms gabapentin and epilepsy, spanning back to the year 1986, produced numerous published reports from randomized, placebo-controlled and open-label trials, as well as case reports. These were reviewed to assess the range of dosing and titration schedules reported. Reports that employed gabapentin doses and titration schedules were selected for review. RESULTS: Our review of this literature suggests improved seizure control at higher gabapentin maintenance dosages (< or =3600 mg/d) than are used today in clinical practice (1800 mg/d) without an increase in the incidence of adverse reactions. Most of the patients who received high dosages (eg, 3600 mg/d) or experienced fast titration rates tolerated gabapentin well. Side effects occurred around the onset of dosing and were reported in some studies to be transient. CONCLUSIONS: Based in the literature here, in most adult patients, gabapentin may be initiated at a dosage of 900 mg/d and titrated to maintenance dosages > or = 3600 mg/d. Children may be treated with gabapentin 23 to 78 mg/kg per day. Based on controlled and open trials, the majority of patients will tolerate gabapentin well enough for an adequate therapeutic assessment. Titration to effect can be accomplished rapidly, if necessary; however, as with other AEDs, optimal seizure control may take months to achieve.
BACKGROUND:Gabapentin is considered a safe and well-tolerated antipileptic drug (AED) with a favorable pharmacokinetic profile and a broad therapeutic index. However, recent studies have used higher doses and faster titration schedules than those used in the pivotal trials that established the efficacy of gabapentin in the treatment of partial seizures. OBJECTIVE: The purposes of this review were to assess the gabapentin titration and dosing regimens that have been published in peer-reviewed journals, to develop dosing recommendations to maximize antiseizure efficacy without compromising tolerability, and to formulate guidelines for an adequate therapeutic assessment of gabapentin dosage efficacy. METHODS: In the absence of sufficient placebo-controlled, double-blind studies, a formal evidence-based assessment could not be performed. However, a MEDLINE search using the search terms gabapentin and epilepsy, spanning back to the year 1986, produced numerous published reports from randomized, placebo-controlled and open-label trials, as well as case reports. These were reviewed to assess the range of dosing and titration schedules reported. Reports that employed gabapentin doses and titration schedules were selected for review. RESULTS: Our review of this literature suggests improved seizure control at higher gabapentin maintenance dosages (< or =3600 mg/d) than are used today in clinical practice (1800 mg/d) without an increase in the incidence of adverse reactions. Most of the patients who received high dosages (eg, 3600 mg/d) or experienced fast titration rates tolerated gabapentin well. Side effects occurred around the onset of dosing and were reported in some studies to be transient. CONCLUSIONS: Based in the literature here, in most adult patients, gabapentin may be initiated at a dosage of 900 mg/d and titrated to maintenance dosages > or = 3600 mg/d. Children may be treated with gabapentin 23 to 78 mg/kg per day. Based on controlled and open trials, the majority of patients will tolerate gabapentin well enough for an adequate therapeutic assessment. Titration to effect can be accomplished rapidly, if necessary; however, as with other AEDs, optimal seizure control may take months to achieve.
Authors: Amit Sood; Jon O Ebbert; Kirk D Wyatt; Ivana T Croghan; Darrell R Schroeder; Richa Sood; J Taylor Hays Journal: Nicotine Tob Res Date: 2010-01-15 Impact factor: 4.244