短效催眠药三唑仑、唑吡坦和佐匹克隆对人体认知能力的影响

INFLUENCE OF SHORT-TERM EFFECT HYPNOTIC TRIAZOLAM, ZOLPIDEM AND ZOPICLONE ON COGNITIVE PERFORMANCE

目的观察正常人服用短效催眠药三唑仑、唑吡坦和佐匹克隆对认知能力的副作用 ,为制定飞行人员的合理用药方案提供科学依据。方法 8名健康男性青年志愿者 ,在 4次试验 (每次间隔 5d)中交叉服用三唑仑 0 .2 5mg、唑吡坦 10mg、佐匹克隆 7.5mg和安慰剂 ,采用随机双盲设计给药 ,分别在服药前 4h、服药后 1h、2h、3h、4h、6h、8h、10h各完成 1次认知能力测试 ,同时观察用药不良反应。测试内容包括 :(1)斯坦福嗜睡量表 ;(2 )单双重任务 (包括四数连加正确率、心理运动能力及两者复合的双重任务 )能力 ;(3)声光刺激反应 (包括声光反应时、声光运动时、临界闪光融合频率和注意分配 )能力。用两因素重复测量的方差分析比较药物间与不同用药后时间认知能力的差别。结果与安慰剂组比较 ,唑吡坦和佐匹克隆在用药后能明显提高斯坦福嗜睡量表分值 (安慰剂组最高 2 .0分 ,两药物组分别达到 4 .0和 3.4分 ) ;唑吡坦、佐匹克隆可明显降低心理运动能力 (分别为 9.2 %和 11.0 % ) ;唑吡坦可明显降低双重任务保持率 ;佐匹克隆可明显降低四数连加正确率和双重任务正确率。三唑仑对各项指标的影响均不显著。结论 3种短效催眠药在用药约 6h后 ,对认知能力的影响消失 ,其中三唑仑的副作用最小。

Objective To investigate the adverse-effect of triazolam, zolpidem, and zopiclone on cognitive ability of healthy young men,so as to provide scientific basis for working out rational scheme for aircrew to use these drugs. Methods Eight male healthy young volunteers experienced a double-blind, crossover design,in which four drugs(placebo, triazolam 0.25 mg, zolpidem 10 mg and zopiclone 7.5 mg) were respectively used in four experiments arranged at intervals of 5 days. Tests including Stanford sleepiness scale, four-digit-addition, psychomotor performance, dual task, visual and auditory reaction time and motion reaction time, attention distribution, and critical flicker fusion frequency were performed 4 h before and 1 h,2 h,3 h,4 h,6 h,8 h,10 h after drug administration. The differences in cognitive ability among drugs or time points after drug administration were determined by analysis of variance. Results Zolpidem, and zopiclone could markedly elevate the scores of Stanford sleepiness scale(SSS) in comparison to placebo. The highest scores of SSS in zolpidem and zopiclone groups were 4.0 and 3.4 respectively. Zolpidem and zopiclone obviously decreased the psychomotor performance by 9.2% and 11.0% respectively.Moreover,zolpidem could obviously decrease the keeping rate of dual task while zopiclone decreased the correct rates of four-digit-addition and dual task. Triazolam had no significant influence on these parameters. Conclusion The effects of these hypnotics on cognitive ability disappeared about 6 h after drugs were taken. Triazolam has minimal side effects.