Eagger S A, Levy R, Sahakian B J
Institute of Psychiatry, Denmark Hill, London, UK.
Lancet. 1991 Apr 27;337(8748):989-92. doi: 10.1016/0140-6736(91)92656-m.
The efficacy and safety of tacrine (tetrahydroaminoacridine) plus lecithin were studied in a randomised, double-blind, placebo-controlled, crossover study. Patients with probable Alzheimer's disease were selected from those attending the memory clinic at a psychiatric hospital. Of the 89 patients included, 24 were withdrawn, 19 because of side-effects, 4 with other illnesses, and 1 for non-compliance. The active treatment was the maximum tolerated dose of tacrine up to 150 mg daily plus 10.8 g lecithin daily. Patients were randomly assigned to active or placebo treatment and crossed over after 13 weeks' treatment and 4 weeks' washout to the other treatment. The main outcome measures were the mini mental state examination (MMSE), the abbreviated mental test score (AMTS), and the carer's rating of the activities of daily living scale. Analysis for the 65 patients who completed the trial showed a significant beneficial effect of tacrine over placebo in the MMSE score (p less than 0.0001; 95% confidence interval for group change on tacrine over that on placebo 1.67-3.71); 29 (45%) patients showed an improvement of 3 or more points on tacrine compared with 7 (11%) during placebo. The findings with the AMTS were similar (p = 0.0001; 95% CI 0.36-1.38) but the ADL score showed no significant treatment effect. There was substantial variation in response among the subjects. Dose-dependent rises in serum liver enzymes were common but reversible. Tacrine produced an improvement in key outcome measures roughly equivalent to the deterioration which might have occurred over 6-12 months. The clinical relevance of the findings is a matter for individual judgment.
在一项随机、双盲、安慰剂对照、交叉研究中，对他克林（四氢氨基吖啶）加卵磷脂的疗效和安全性进行了研究。可能患有阿尔茨海默病的患者是从一家精神病医院记忆门诊的就诊者中挑选出来的。在纳入的89名患者中，有24名退出，19名是因为副作用，4名患有其他疾病，1名是因为不依从。积极治疗是他克林的最大耐受剂量，每日最高达150毫克加每日10.8克卵磷脂。患者被随机分配接受积极治疗或安慰剂治疗，在接受13周治疗和4周洗脱期后交叉接受另一种治疗。主要结局指标是简易精神状态检查（MMSE）、简易智力测验评分（AMTS）以及照顾者对日常生活活动量表的评分。对完成试验的65名患者的分析显示，他克林在MMSE评分上比安慰剂有显著的有益效果（p<0.0001；他克林组相对于安慰剂组变化的95%置信区间为1.67 - 3.71）；与安慰剂治疗期间7名（11%）患者相比，29名（45%）患者在接受他克林治疗时MMSE评分提高了3分或更多。AMTS的结果相似（p = 0.0001；95%CI 0.36 - 1.38），但日常生活活动量表评分未显示出显著的治疗效果。受试者之间的反应存在很大差异。血清肝酶剂量依赖性升高很常见但可逆。他克林在关键结局指标上产生的改善大致相当于6 - 12个月内可能发生的恶化。这些发现的临床相关性有待个人判断。
