Frisher Martin, Gibbons Nicholas, Bashford James, Chapman Steve, Weich Scott
Division of Mental Health and Wellbeing, Warwick Medical School, University of Warwick, Coventry, UK.
Age Ageing. 2016 Nov;45(6):801-806. doi: 10.1093/ageing/afw123. Epub 2016 Jul 26.
although melatonin prescribing in England has been increasing in recent years, there have been no large scale studies on the safety of melatonin compared to other medical treatments for insomnia. The primary aim of this study was to examine the association between exposure to melatonin, hypnotic benzodiazepines (temazepam, nitrazepam) or Z-drugs (zolpidem, zopiclone) and fracture risk.
retrospective cohort study.
309 general practices contributing to The Health Improvement Network (THIN) between 2008 and 2013.
1,377 patients aged 45 years and older prescribed melatonin; 880 patients prescribed hypnotic benzodiazepines; 1,148 patients prescribed Z-drugs and 2,752 unexposed controls matched by age, gender and practice.
fracture following prescription of study drugs ascertained from practice records.
the unadjusted hazard ratios for fracture during the follow-up period were 1.90 (95% CI 1.41-2.57) for melatonin, 1.70 (95% CI 1.18-2.46) for hypnotic benzodiazepines and 2.03 (95% CI 1.45-2.84) for Z-drugs. After adjustment for 26 covariates, the hazard ratios were 1.44 (95% CI 1.01-2.04) for melatonin, 1.26 (95% CI 0.82-1.92) for hypnotic benzodiazepines and 1.52 (95% CI 1.04-2.23) for Z-drugs. Only patients with three or more melatonin prescriptions had elevated risk. The mean time to fracture was 1.04 years and there was no significant difference in mean time to fracture between the cohorts.
in this large cohort of patients attending UK primary care, prescriptions for melatonin and Z-drugs were associated with a significantly increased risk of fracture. With the use of melatonin increasing steadily overtime, this study adds to the literature on the safety profile of this drug.
尽管近年来英国褪黑素的处方量一直在增加，但与其他治疗失眠的药物相比，尚未有关于褪黑素安全性的大规模研究。本研究的主要目的是探讨服用褪黑素、催眠苯二氮䓬类药物（替马西泮、硝西泮）或Z类药物（唑吡坦、佐匹克隆）与骨折风险之间的关联。
回顾性队列研究。
2008年至2013年间向健康改善网络（THIN）提供数据的309家全科诊所。
1377名45岁及以上开具褪黑素处方的患者；880名开具催眠苯二氮䓬类药物处方的患者；1148名开具Z类药物处方的患者以及2752名按年龄、性别和诊所进行匹配的未暴露对照组。
根据诊所记录确定研究药物处方后的骨折情况。
随访期间，未调整的骨折风险比分别为：褪黑素组1.90（95%可信区间1.41 - 2.57），催眠苯二氮䓬类药物组1.70（95%可信区间1.18 - 2.46），Z类药物组2.03（95%可信区间1.45 - 2.84）。在对26个协变量进行调整后，风险比分别为：褪黑素组1.44（95%可信区间1.01 - 2.04），催眠苯二氮䓬类药物组1.26（95%可信区间0.82 - 1.92），Z类药物组1.52（95%可信区间1.04 - 2.23）。只有开具三种或更多褪黑素处方的患者风险升高。骨折的平均时间为1.04年，各队列之间骨折的平均时间无显著差异。
在这一参加英国初级医疗的大型患者队列中，褪黑素和Z类药物的处方与骨折风险显著增加相关。随着时间的推移，褪黑素的使用稳步增加，本研究补充了关于该药物安全性的文献。
