Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospitals, Frederiksberg, Denmark (Osler); Section for Epidemiology, Department of Public Health, University of Copenhagen (Osler); Psychiatric Center Copenhagen, Department O, Rigshospitalet, Copenhagen (Jørgensen); and Institute of Clinical Medicine, University of Copenhagen (Jørgensen).
Am J Psychiatry. 2020 Jun 1;177(6):497-505. doi: 10.1176/appi.ajp.2019.19030315. Epub 2020 Apr 7.
Benzodiazepines and Z-drugs are two of the most prescribed agents worldwide. However, because of their cognitive side effects, the question of their influence on the risk of dementia has been raised. The authors examined the association of benzodiazepines, Z-drugs, and other anxiolytics with incident dementia in patients with affective disorders.
The authors conducted a cohort and nested case-control study of 235,465 patients over age 20 who were identified in the Danish National Patient Registry as having had a first-time hospital contact for an affective disorder between 1996 and 2015. From the Danish National Prescription Registry, information was obtained on all prescriptions for benzodiazepines, Z-drugs, and other anxiolytics, and patients were followed for incident dementia (defined by hospital discharge diagnosis or acetylcholinesterase inhibitor use). Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios and odds ratios with adjustment for sociodemographic and clinical variables.
A total of 75.9% (N=171,287) of patients had any use of benzodiazepines or Z-drugs, and during the median follow-up of 6.1 years (interquartile range, 2.7-11), 9,776 (4.2%) patients were diagnosed with dementia. Any use of benzodiazepines or Z-drugs showed no association with dementia after multiple adjustments in either the cohort analysis or a nested case-control design. In the cohort analysis, the number of prescriptions and the cumulated dose of benzodiazepines or Z-drugs at baseline were not associated with dementia. In the nested case-control study, where prescriptions were counted from 1995 until 2 years before the index date, there was a slightly higher odds ratio of dementia in patients with the lowest use of benzodiazepines or Z-drugs (odds ratio=1.08, 95% CI=1.01, 1.15) compared with no lifetime use. However, patients with the highest use had the lowest odds of developing dementia (odds ratio=0.83, 95% CI=0.77, 0.88).
This large cohort study did not reveal associations between use of benzodiazepines or Z-drugs and subsequent dementia, even when exposures were cumulated or divided into long- and short-acting drugs. Some results were compatible with a protective effect.
苯二氮䓬类药物和 Z 类药物是全球应用最广泛的两种药物。然而，由于其认知方面的副作用，人们提出了它们对痴呆风险的影响的问题。作者研究了苯二氮䓬类药物、Z 类药物和其他抗焦虑药与情感障碍患者新发痴呆的关系。
作者对 20 岁以上的 235465 名患者进行了队列和嵌套病例对照研究，这些患者是通过丹麦国家患者登记处识别的，他们在 1996 年至 2015 年间首次因情感障碍住院。从丹麦国家处方登记处获取了所有苯二氮䓬类药物、Z 类药物和其他抗焦虑药的处方信息，并且对患者进行了新发痴呆（通过医院出院诊断或乙酰胆碱酯酶抑制剂使用确定）的随访。使用 Cox 比例风险和条件逻辑回归模型，在调整了社会人口统计学和临床变量后，计算了风险比和优势比。
共有 75.9%（N=171287）的患者使用过苯二氮䓬类药物或 Z 类药物，在中位随访 6.1 年（四分位距，2.7-11）期间，9776 名（4.2%）患者被诊断为痴呆。在队列分析或嵌套病例对照设计中，经过多次调整后，使用苯二氮䓬类药物或 Z 类药物与痴呆均无关联。在队列分析中，基线时苯二氮䓬类药物或 Z 类药物的处方数量和累积剂量与痴呆无关。在嵌套病例对照研究中，从 1995 年开始计算处方，直到索引日期前 2 年，与终生未使用相比，使用苯二氮䓬类药物或 Z 类药物最低的患者痴呆的优势比略高（优势比=1.08，95%CI=1.01，1.15）。然而，使用最多的患者患痴呆的可能性最低（优势比=0.83，95%CI=0.77，0.88）。
这项大型队列研究并未发现使用苯二氮䓬类药物或 Z 类药物与随后的痴呆之间存在关联，即使将暴露情况累积或分为长效和短效药物。有些结果与保护作用一致。
