Allain Hervé, Bentué-Ferrer Danièle, Polard Elisabeth, Akwa Yvette, Patat Alain
Laboratory of Experimental and Clinical Pharmacology, Pôle des Neurosciences and Centre Memory Resources Research (CMRR), Faculty of Medicine, University of Rennes 1, Rennes Cedex, France.
Drugs Aging. 2005;22(9):749-65. doi: 10.2165/00002512-200522090-00004.
The aim of this review is to establish the relationship between treatment with hypnotics and the risk of postural instability and as a consequence, falls and hip fractures, in the elderly. A review of the literature was performed through a search of the MEDLINE, Ingenta and PASCAL databases from 1975 to 2005. We considered as hypnotics only those drugs approved for treating insomnia, i.e. some benzodiazepines and the more recently launched 'Z'-compounds, i.e. zopiclone, zolpidem and zaleplon. Large-scale surveys consistently report increases in the frequency of falls and hip fractures when hypnotics are used in the elderly (2-fold risk). Benzodiazepines are the major class of hypnotics involved in this context; falls and fractures in patients taking Z-compounds are less frequently reported, and in this respect, zolpidem is considered as at risk in only one study. It is important to note, however, that drug adverse effect relationships are difficult to establish with this type of epidemiological data-mining. On the other hand, data obtained in laboratory settings, where confounding factors can be eliminated, prove that benzodiazepines are the most deleterious hypnotics at least in terms of their effects on body sway. Z-compounds are considered safer, probably because of their pharmacokinetic properties as well as their selective pharmacological activities at benzodiazepine-1 (BZ(1)) receptors. The effects of hypnotics on balance, gait and equilibrium are the consequence of differential negative impacts on vigilance and cognitive functions, and are highly dose- and time-dependent. Z-compounds have short half-lives and have less cognitive and residual effects than older medications. Some practical rules need to be followed when prescribing hypnotics in order to prevent falls and hip fractures as much as possible in elderly insomniacs, whether institutionalised or not. These are: (i) establish a clear diagnosis of the sleep disorder; (ii) take into account chronic conditions leading to balance and gait difficulties (motor and cognitive status); (iii) search for concomitant prescription of psychotropics and sedatives; (iv) use half the recommended adult dosage; and (v) declare any adverse effect to pharmacovigilance centres. Comparative pharmacovigilance studies focused on the impact of hypnotics on postural stability are very much needed.
本综述的目的是确定使用催眠药与老年人姿势不稳风险之间的关系,以及由此导致的跌倒和髋部骨折风险。通过检索1975年至2005年的MEDLINE、Ingenta和PASCAL数据库对文献进行了综述。我们仅将那些被批准用于治疗失眠的药物视为催眠药,即某些苯二氮䓬类药物以及最近推出的“Z类化合物”,即佐匹克隆、唑吡坦和扎来普隆。大规模调查一致报告,老年人使用催眠药时跌倒和髋部骨折的发生率会增加(风险增加两倍)。苯二氮䓬类药物是与此相关的主要催眠药类别;服用Z类化合物的患者跌倒和骨折的报告较少,在这方面,只有一项研究认为唑吡坦有风险。然而,需要注意的是,用这种类型的流行病学数据挖掘很难确定药物不良反应之间的关系。另一方面,在可以消除混杂因素的实验室环境中获得的数据证明,至少就其对身体摇摆的影响而言,苯二氮䓬类药物是最有害的催眠药。Z类化合物被认为更安全,这可能是由于它们的药代动力学特性以及它们在苯二氮䓬-1(BZ(1))受体上的选择性药理活性。催眠药对平衡、步态和平衡的影响是对警觉性和认知功能的不同负面影响的结果,并且高度依赖剂量和时间。Z类化合物半衰期短,与 older medications相比,认知和残留效应较小。在为老年失眠症患者(无论是否住院)开催眠药时,需要遵循一些实用规则,以尽可能预防跌倒和髋部骨折。这些规则是:(i)明确诊断睡眠障碍;(ii)考虑导致平衡和步态困难的慢性疾病(运动和认知状态);(iii)查找是否同时开具了精神药物和镇静剂;(iv)使用推荐成人剂量的一半;以及(v)向药物警戒中心报告任何不良反应。非常需要开展关注催眠药对姿势稳定性影响的比较药物警戒研究。