Gabapentin and cognition: A double blind, dose ranging, placebo controlled study in refractory epilepsy
Gabapentin and cognition: A double blind, dose ranging, placebo controlled study in refractory epilepsy
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DOI：
10.1136/jnnp.62.4.372
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发表时间：
1997-04-01
影响因子：
11
通讯作者：
Brodie, MJ
中科院分区：
文献类型：
--
作者：
Leach, JP;Girvan, J;Brodie, MJ
目的-评估不同剂量的加巴喷丁（GBP）对癫痫患者认知功能的影响。方法-27例难治性部分性癫痫患者开始了一项双盲、剂量范围、安慰剂对照、交叉研究。每个治疗阶段持续三个月，在此期间，GBP或匹配的安慰剂的剂量以四周为间隔逐步增加（1200 mg/天、1800 mg/天和2400 mg/天，每日三次）。在每四周结束时进行精神和记忆测试，此时患者还完成认知，疲劳，担忧，脾气和烦躁的主观测量。视觉模拟量表被用来评估困倦和问卷调查，以衡量的严重程度的副作用。结果-在21例完成研究，GBP产生了显着减少中位每月癫痫发作频率从7至4.3（P = 0.02），减少是最明显的继发性全身性癫痫发作（从1.0至0.3，P = 0.01）。43%的患者报告在所有GBP剂量下癫痫发作频率至少减少50%。1200、1800和2400 mg/天剂量组GBP的平均（SD）血浆浓度分别为4.7（2.6）、6.8（3.8）和8.6（3.3）mg/l。药物对复合精神和记忆评分没有影响，也没有改变任何自我评估分项评分。与匹配的安慰剂相比，每日2400 mg GBP治疗期间的平均嗜睡（P = 0.03）评分较高。复合心理学（r =-0.47，P < 0.01），疲劳（r = 0.42，P < 0.01），副作用（r = 0.61，P < 0.001）评分与癫痫发作频率显著相关，但与GBP剂量无关。GBP是一种耐受性良好且有效的抗癫痫药物，对认知没有可测量的影响，但在最高剂量时确实产生镇静作用。这项研究也支持癫痫发作可能导致认知障碍的建议。
Objective - To assess the effect of different doses of gabapentin (GBP) on cognitive function in treated epileptic patients.Methods - Twenty seven patients with refractory partial seizures commenced a double blind, dose ranging, placebo controlled, crossover study of adjuvant GBP. Each treatment phase lasted three months, during which the dose of GBP or matched placebo was increased stepwise at intervals of four weeks (1200 mg/day, 1800 mg/day, and 2400 mg/day in three daily doses). Psychomotor and memory testing was carried out at the end of each four week period, at which time the patient also completed subjective measures of cognition, fatigue, worry, temper, and dysphoria. A visual analogue scale was used to assess drowsiness and a questionnaire was employed to gauge the severity of side effects.Results - In the 21 patients completing the study, GBP produced a significant reduction in median monthly seizure frequency from 7 to 4.3 (P = 0.02), the decrease being most pronounced for secondarily generalised seizures (from 1.0 to 0.3, P = 0.01). Forty three per cent of patients reported a reduction in seizure frequency of at least 50% throughout all GBP doses. Mean (SD) plasma concentrations of GBP at 1200, 1800, and 2400 mg/day were 4.7 (2.6), 6.8 (3.8), and 8.6 (3.3) mg/l respectively. The drug had no effect on composite psychomotor and memory scores; nor was there alteration in any self assessment subscore. The mean drowsiness (P = 0.03) score was higher during treatment with 2400 mg GBP daily compared with matched placebo. Composite psychomotor (r = -0.47, P < 0.01), tiredness (r = 0.42, P < 0.01), and side effect (r = 0.61, P < 0.001) scores correlated significantly with seizure frequency but not with GBP dose.Conclusion - GBP is a well tolerated and effective antiepileptic drug which had no measurable effect on cognition but did produce sedation at the highest dose. This study also supports the suggestion that seizures can cause cognitive impairment.