De Vanna Maurizio, Rubiera Marta, Onor Maria Luisa, Aguglia Eugenio
Department of Clinical Psychiatry, Faculty of Medicine, University of Trieste, Trieste, Italy.
Clin Drug Investig. 2007;27(5):325-32. doi: 10.2165/00044011-200727050-00003.
Sleep architecture changes with age, both in terms of efficiency and total duration of sleep. Hypnotic benzodiazepines promote rapid onset of sleep, uninterrupted sleep and longer duration of sleep in the absence of carryover sedation the following morning; therefore, these may be appropriate for use in older patients. This study was performed to evaluate the efficacy and safety of lormetazepam in elderly patients with primary insomnia when used in association with sleep hygiene training (SHT). The impact of restored sleep on daily sleepiness was also investigated.
In this open-label study, 30 elderly outpatients with insomnia were randomised to receive 2 weeks of treatment with lormetazepam 0.5mg + SHT or SHT alone, followed by a 1-week observation period. Details on sleep latency, number of awakenings and freshness on awakening were recorded by patients in a daily sleep diary. The Epworth Sleepiness Scale (ESS) and Stanford Sleepiness Scale (SSS) were used to measure daily sleepiness.
Addition of lormetazepam to SHT improved all sleep parameters measured compared with SHT alone. Mean duration of sleep improved significantly from baseline (mean rank=1.00) in the lormetazepam + SHT group after 2 weeks of treatment (mean rank 2.87; Friedmann test=27.448; p<0.001), but declined significantly in the group receiving SHT alone (from mean rank 2.33 to 1.57; Friedmann test=6.465; p<0.05). Mean duration of sleep increased by approximately 150 minutes each night in the lormetazepam + SHT group but decreased by more than 30 minutes in the SHT-only group. Improvement in sleep quality from baseline was statistically significant only in the lormetazepam + SHT group: for both deepness of sleep and the perception of awakening refreshed, mean scores increased from approximately 3 at baseline to approximately 8 (on a scale of 1-10) after 2 weeks in this group. Sleep latency also decreased significantly in the lormetazepam + SHT group: after 2 weeks, on average patients were awakening less than once per night. SSS and ESS scores also improved significantly in the lormetazepam + SHT group; in contrast, in the SHT-only group, the mean ESS score worsened significantly from baseline and the mean SSS score remained relatively constant. No rebound insomnia was reported during follow-up in patients in the lormetazepam group. Vital signs did not change from baseline and no adverse events were reported for either group.
Management of insomnia in the elderly appears to have a better outcome when pharmacotherapy is combined with SHT rather than SHT alone. The earlier improvement in sleep quality with lormetazepam when used in combination with a sleep training programme may help to maintain adherence to treatment.
睡眠结构会随着年龄增长而发生变化，在睡眠效率和总睡眠时间方面均是如此。催眠性苯二氮䓬类药物可促进快速入睡、实现睡眠不间断，并在次日早晨无残留镇静作用的情况下延长睡眠时间；因此，这些药物可能适用于老年患者。本研究旨在评估氯美扎酮联合睡眠卫生训练（SHT）用于老年原发性失眠患者时的疗效和安全性。同时还研究了恢复睡眠对日常嗜睡情况的影响。
在这项开放标签研究中，30名老年失眠门诊患者被随机分为两组，分别接受为期2周的氯美扎酮0.5mg + SHT治疗或单纯SHT治疗，随后为1周的观察期。患者通过每日睡眠日记记录睡眠潜伏期、觉醒次数及觉醒时的清醒程度等详细信息。采用爱泼沃斯思睡量表（ESS）和斯坦福嗜睡量表（SSS）来测量日常嗜睡情况。
与单纯SHT相比，氯美扎酮联合SHT改善了所有测量的睡眠参数。治疗2周后，氯美扎酮 + SHT组的平均睡眠时间较基线有显著改善（平均秩次 = 1.00）（平均秩次2.87；Friedmann检验 = 27.448；p < 0.001），而单纯接受SHT治疗的组则显著下降（从平均秩次2.33降至1.57；Friedmann检验 = 6.465；p < 0.05）。氯美扎酮 + SHT组每晚的平均睡眠时间增加了约150分钟，而单纯SHT组则减少了超过30分钟。仅在氯美扎酮 + SHT组，睡眠质量从基线的改善具有统计学意义：在该组中，睡眠深度和觉醒后清醒感的平均评分在2周后从基线时的约3分提高到了约8分（1 - 10分制）。氯美扎酮 + SHT组的睡眠潜伏期也显著缩短：2周后，患者平均每晚觉醒次数少于1次。氯美扎酮 + SHT组的SSS和ESS评分也显著改善；相比之下，单纯SHT组的平均ESS评分较基线显著恶化，而平均SSS评分保持相对稳定。氯美扎酮组患者在随访期间未报告反弹性失眠。两组患者的生命体征与基线相比均无变化，且均未报告不良事件。
老年失眠的管理在药物治疗与SHT联合使用时似乎比单纯使用SHT具有更好的效果。氯美扎酮与睡眠训练计划联合使用时，睡眠质量能更早得到改善，这可能有助于维持患者对治疗的依从性。
