Staner Luc, Ertlé Stéphane, Boeijinga Peter, Rinaudo Gilbert, Arnal Marie Agnès, Muzet Alain, Luthringer Rémy
FORENAP-Institute for Research in Neurosciences, Neuropharmacology and Psychiatry, Centre Hospitalier, Rouffach, France.
Psychopharmacology (Berl). 2005 Oct;181(4):790-8. doi: 10.1007/s00213-005-0082-8. Epub 2005 Sep 29.
Most studies that investigated the next-day residual effects of hypnotic drugs on daytime driving performances were performed on healthy subjects and after a single drug administration.
In the present study, we further examine whether the results of these studies could be generalised to insomniac patients and after repeated drug administration.
Single and repeated (7 day) doses of zolpidem (10 mg), zopiclone (7.5 mg), lormetazepam (1 mg) or placebo were administered at bedtime in a crossover design to 23 patients (9 men and 14 women aged 38.8+/-2.0 years) with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) primary insomnia. Driving tests were performed 9-11 h post-dose.
Results showed that treatment effects were evidenced for subjective sleep, for driving abilities, and for electroencephalogram (EEG) recorded before (resting EEG) and during the driving simulation test (driving EEG). Compared to placebo, zopiclone increased the number of collisions and lormetazepam increased deviation from speed limit and deviation from absolute speed, whereas zolpidem did not differentiate from placebo on these analyses. EEG recordings showed that in contrast to zolpidem, lormetazepam and zopiclone induced typical benzodiazepine-like alterations, suggesting that next-day poor driving performance could relate to a prolonged central nervous system effect of these two hypnotics.
The present results corroborate studies on healthy volunteers showing that residual effects of hypnotics increase with their half-lives. The results further suggest that drugs preserving physiological EEG rhythms before and during the driving simulation test 9-11 h post-dose, such as zolpidem, do not influence next-day driving abilities.
大多数关于催眠药物对日间驾驶表现的次日残留效应的研究是在健康受试者身上进行的,且是在单次给药后。
在本研究中,我们进一步探讨这些研究结果是否可以推广到失眠症患者以及多次给药后。
采用交叉设计,在睡前对23例符合《精神障碍诊断与统计手册》第四版(DSM-IV)原发性失眠诊断标准的患者(9名男性和14名女性,年龄38.8±2.0岁)给予单次和重复(7天)剂量的唑吡坦(10毫克)、佐匹克隆(7.5毫克)、氯美扎酮(1毫克)或安慰剂。给药后9至11小时进行驾驶测试。
结果表明,在主观睡眠、驾驶能力以及驾驶模拟测试前(静息脑电图)和测试期间(驾驶脑电图)记录的脑电图方面均显示出治疗效果。与安慰剂相比,佐匹克隆增加了碰撞次数,氯美扎酮增加了速度限制偏差和绝对速度偏差,而在这些分析中唑吡坦与安慰剂没有差异。脑电图记录显示,与唑吡坦不同,氯美扎酮和佐匹克隆诱导了典型的苯二氮卓类改变,这表明次日驾驶表现不佳可能与这两种催眠药对中枢神经系统的持久作用有关。
本研究结果证实了对健康志愿者的研究,即催眠药的残留效应随其半衰期增加。结果还进一步表明,在给药后9至11小时的驾驶模拟测试前和测试期间保持生理脑电图节律的药物,如唑吡坦,不会影响次日的驾驶能力。