Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, Hospital Pharmacy, University of Basel, Spitalstrasse 26, 4031, Basel, Switzerland.
Hospital Pharmacy, University Hospital Basel, Basel, Switzerland.
CNS Drugs. 2017 Mar;31(3):245-251. doi: 10.1007/s40263-016-0404-x.
A possible association between benzodiazepine use and Alzheimer's disease (AD) has been hypothesized in previous studies.
Using claims data from the Helsana Group, a large Swiss health insurance provider, we examined the association between previous benzodiazepine use and the risk of AD.
We conducted a matched case-control study and identified 1438 incident AD cases between 2013 and 2014 based on recorded first-time use of drugs used to treat AD [i.e., acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and the N-methyl-D-aspartate receptor antagonist memantine] and matched one control to each case on age, sex, index date, and residence (canton). Because the initiation of benzodiazepine use shortly before the AD diagnosis date may occur as a result of symptomatic treatment of prodromal symptoms of early major neurocognitive disorder, we introduced an induction period of 2 years before the AD diagnosis date. Additionally, we categorized medication use by duration of use prior to the index date using prescriptions. We applied conditional logistic regression analyses to calculate odds ratios with 95% confidence intervals and adjusted for use of antidepressants.
The crude odds ratio (95% confidence interval) of developing AD for patients starting benzodiazepine treatment was 1.71 (1.17-2.99) in the year before diagnosis and 1.19 (0.82-1.72) in the third year before diagnosis. After accounting for benzodiazepine use initiated during the prodromal phase, benzodiazepine use was not associated with an increased risk of developing AD; long-term benzodiazepine use (≥30 prescriptions) yielded an adjusted odds ratio of 0.78 (0.53-1.14).
After taking into consideration a possible protopathic bias in the 2 years preceding the AD diagnosis date, benzodiazepine use was not associated with an increased risk of developing AD.
先前的研究假设，苯二氮䓬类药物的使用与阿尔茨海默病（AD）之间可能存在关联。
利用瑞士大型健康保险公司 Helsana Group 的理赔数据，我们检验了先前使用苯二氮䓬类药物与 AD 风险之间的关系。
我们进行了一项匹配的病例对照研究，根据首次使用治疗 AD 的药物（即乙酰胆碱酯酶抑制剂[多奈哌齐、利斯的明和加兰他敏]和 N-甲基-D-天冬氨酸受体拮抗剂美金刚）的记录，确定了 2013 年至 2014 年间的 1438 例 AD 发病病例，并根据年龄、性别、索引日期和居住地（州）与每位病例匹配了 1 名对照。由于在 AD 诊断日期之前不久开始使用苯二氮䓬类药物可能是对早期主要神经认知障碍前驱症状的对症治疗，我们引入了一个 AD 诊断日期前 2 年的诱导期。此外，我们还根据索引日期前的使用时间长短对药物使用进行了分类。我们应用条件逻辑回归分析计算了比值比及其 95%置信区间，并调整了抗抑郁药的使用。
在诊断前 1 年开始使用苯二氮䓬类药物的患者发生 AD 的粗比值比（95%置信区间）为 1.71（1.17-2.99），在诊断前 3 年为 1.19（0.82-1.72）。在考虑到前驱期开始的苯二氮䓬类药物使用后，苯二氮䓬类药物使用与 AD 发病风险的增加无关；长期苯二氮䓬类药物使用（≥30 剂）的调整比值比为 0.78（0.53-1.14）。
在考虑到 AD 诊断日期前 2 年可能存在的前驱性偏倚后，苯二氮䓬类药物使用与 AD 发病风险无关。
