McLean Michael J, Gidal Barry E
Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee 37212, USA.
Clin Ther. 2003 May;25(5):1382-406. doi: 10.1016/s0149-2918(03)80127-3.
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.
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.
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.
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.
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.
加巴喷丁被认为是一种安全且耐受性良好的抗癫痫药物（AED），具有良好的药代动力学特征和较宽的治疗指数。然而，最近的研究使用的剂量和滴定方案比确定加巴喷丁治疗部分性癫痫疗效的关键试验中所使用的更高、更快。
本综述的目的是评估在同行评审期刊上发表的加巴喷丁滴定和给药方案，制定给药建议以在不影响耐受性的情况下最大化抗癫痫疗效，并制定加巴喷丁剂量疗效充分治疗评估的指南。
由于缺乏足够的安慰剂对照双盲研究，无法进行正式的循证评估。然而，使用“加巴喷丁”和“癫痫”作为检索词对MEDLINE进行检索，检索时间跨度至1986年，检索出了许多来自随机、安慰剂对照和开放标签试验的已发表报告以及病例报告。对这些报告进行审查以评估所报告的给药和滴定方案范围。选择采用加巴喷丁剂量和滴定方案的报告进行审查。
我们对该文献的综述表明，与目前临床实践中使用的剂量（1800mg/d）相比，加巴喷丁维持剂量较高（≤3600mg/d）时癫痫控制得到改善，且不良反应发生率未增加。大多数接受高剂量（如3600mg/d）或经历快速滴定速率的患者对加巴喷丁耐受性良好。副作用在给药开始时出现，一些研究报告称这些副作用是短暂的。
基于此处的文献，在大多数成年患者中，加巴喷丁可起始剂量为900mg/d，并滴定至维持剂量≥3600mg/d。儿童可每日使用23至78mg/kg的加巴喷丁进行治疗。基于对照和开放试验结果，大多数患者对加巴喷丁耐受性良好，足以进行充分的治疗评估。如有必要，可迅速滴定至有效剂量；然而，与其他抗癫痫药物一样，可能需要数月才能实现最佳癫痫控制。
