Martin R, Meador K, Turrentine L, Faught E, Sinclair K, Kuzniecky R, Gilliam F
Department of Neurology, UAB Epilepsy Center, University of Alabama at Birmingham, 1719 6th Avenue South, Birmingham, AL 35294-0021, U.S.A.
Epilepsia. 2001 Jun;42(6):764-71. doi: 10.1046/j.1528-1157.2001.33300.x.
This study compared the cognitive effects of carbamazepine (CBZ) and gabapentin (GBP) in healthy senior adults by using a randomized, double-blind crossover design.
Thirty-four senior adults were randomized to receive one of the two drugs followed by a 5-week treatment period. A 4-week washout phase preceded initiation of the second drug. Antiepileptic drugs (AEDs) were titrated to target doses of either CBZ (800 mg/day) or GBP (2,400 mg/day). Primary outcome measures were standardized neuropsychological tests of attention/vigilance, psychomotor speed, motor speed, verbal and visual memory, and the Profile of Mood State (POMS), yielding a total of 17 variables. Each subject received cognitive testing at predrug baseline, end of first drug phase, end of second drug phase, and 4 weeks after completion of the second drug phase.
Fifteen senior adults (mean age, 66.5 years; range, 59-76 years) completed the study. Seniors completing the study did not differ significantly from noncompleting seniors in terms of demographic features or baseline cognitive performances. Fifteen of the 19 seniors not completing the study dropped out while receiving CBZ. Adverse events were frequently reported for both AEDs, although they were more common for CBZ. Mean serum levels for the completers were within midrange clinical doses (CBZ, 6.8 microg/ml; GBP, 7.1 microg/ml). Significant differences between CBZ and GBP were found for only one of 11 cognitive variables, with better attention/vigilance for GBP, although the effect was modest. Performances on the nondrug average were significantly better on 45% of cognitive variables compared with CBZ and 36% compared with GBP. The overall pattern of means favored GBP over CBZ on 15 of 17 (p < 0.001), nondrug over CBZ on 17 of 17 (p < 0.0000), and nondrug over GBP on eight of 17 (NS).
Mild cognitive effects were found for both AEDs compared with the nondrug average condition. The magnitude of difference between the two AEDs across the cognitive variables was modest. Self-reported mood was not significantly affected by either AED. However, overall tolerability and side-effect profile of CBZ were poorer than those of GBP in senior adults at doses and titration rates reported in this study.
本研究采用随机、双盲交叉设计,比较卡马西平(CBZ)和加巴喷丁(GBP)对健康老年人的认知影响。
34名老年人被随机分为两组,分别接受两种药物中的一种,为期5周的治疗期。在开始第二种药物治疗前有4周的洗脱期。抗癫痫药物(AEDs)滴定至CBZ(800毫克/天)或GBP(2400毫克/天)的目标剂量。主要结局指标是注意力/警觉性、精神运动速度、运动速度、言语和视觉记忆的标准化神经心理学测试,以及情绪状态量表(POMS),共产生17个变量。每个受试者在用药前基线、第一个药物阶段结束、第二个药物阶段结束以及第二个药物阶段完成后4周接受认知测试。
15名老年人(平均年龄66.5岁;范围59 - 76岁)完成了研究。完成研究的老年人在人口统计学特征或基线认知表现方面与未完成研究的老年人没有显著差异。19名未完成研究的老年人中有15名在接受CBZ治疗时退出。两种AEDs均频繁报告不良事件,尽管CBZ更为常见。完成研究的受试者的平均血清水平在临床剂量范围内(CBZ,6.8微克/毫升;GBP,7.1微克/毫升)。在11个认知变量中,仅发现CBZ和GBP之间有一个显著差异,GBP的注意力/警觉性更好,尽管效果不显著。与CBZ相比,45%的认知变量在非药物平均水平上表现显著更好;与GBP相比,36%的认知变量在非药物平均水平上表现显著更好。在17个变量中的15个变量上,均值的总体模式显示GBP优于CBZ(p < 0.001),在17个变量中的17个变量上,非药物状态优于CBZ(p < 0.0000),在17个变量中的8个变量上,非药物状态优于GBP(无显著性差异)。
与非药物平均状态相比,两种AEDs均发现有轻度认知影响。两种AEDs在认知变量上的差异幅度不大。两种AEDs均未显著影响自我报告的情绪。然而,在本研究报告的剂量和滴定率下,CBZ在老年人中的总体耐受性和副作用情况比GBP差。