Kuopio Research Centre for Geriatric Care, University of Eastern Finland, Kuopio, Finland.
School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Int J Geriatr Psychiatry. 2018 Apr;33(4):583-590. doi: 10.1002/gps.4821. Epub 2017 Nov 15.
To investigate the risk of death associated with new benzodiazepine and related drug (BZDR) use in a nationwide cohort of persons with Alzheimer disease (AD).
The register-based MEDALZ cohort, including all community-dwelling Finns diagnosed with AD during 2005 to 2011 (n = 70 718), was used. Clinically verified AD diagnoses were obtained from the Special Reimbursement Register. Drug use periods were modeled from BZDR purchases, derived from the Prescription Register. To study new users, persons who had any BZDR use during the year preceding the AD diagnosis were excluded. For each person initiating BZDR use (n = 10 380), 2 nonusers (n = 20 760) were matched on age, gender, and time since AD diagnosis. The outcome was 180-day mortality, and BZDR use was compared with nonuse with Cox regression. Multivariable analyses were adjusted for Charlson comorbidity index, socioeconomic position, hip fractures, psychiatric disorders, substance abuse, stroke, and other psychotropic drug use.
During the follow-up, 5 excess deaths per 100 person-years occurred during BZDR use in comparison to nonuse, and mortality rates were 13.4 (95% confidence interval [CI], 12.2-14.5) and 8.5 (95% CI, 7.9-9.1), respectively. Benzodiazepine and related drug use was associated with an increased risk of death (adjusted hazard ratio = 1.4 [95% CI, 1.2-1.6]), and the association was significant from the initiation of use. Benzodiazepine use was associated with an increased risk of death, whereas benzodiazepine-related drug use was not.
Benzodiazepine and related drug use was associated with an increased risk of death in persons with AD. Our results support treatment guidelines stating that nonpharmacological approaches should be the first-line option for symptomatic treatment of AD.
在一项针对阿尔茨海默病（AD）患者的全国性队列研究中，调查新苯二氮䓬类和相关药物（BZDR）使用与死亡风险的关系。
本研究使用基于登记的 MEDALZ 队列，该队列包括 2005 年至 2011 年间在社区居住的所有被诊断为 AD 的芬兰人（n=70718）。AD 的临床确诊诊断来自特殊报销登记处。药物使用期通过处方登记处获得的 BZDR 购买情况建模。为了研究新使用者，排除了在 AD 诊断前一年内有任何 BZDR 使用的人。对于每个开始使用 BZDR 的人（n=10380），按年龄、性别和 AD 诊断后时间匹配 2 名未使用者（n=20760）。结果是 180 天死亡率，并用 Cox 回归比较 BZDR 使用与未使用。多变量分析调整了 Charlson 合并症指数、社会经济地位、髋部骨折、精神障碍、物质滥用、中风和其他精神药物使用。
在随访期间，与未使用者相比，BZDR 使用期间每 100 人年发生 5 例超额死亡，死亡率分别为 13.4（95%置信区间[CI]，12.2-14.5）和 8.5（95%CI，7.9-9.1）。苯二氮䓬类和相关药物的使用与死亡风险增加相关（调整后的危险比=1.4[95%CI，1.2-1.6]），且从使用开始就有显著关联。苯二氮䓬类药物的使用与死亡风险增加相关，而苯二氮䓬类相关药物的使用则没有。
在 AD 患者中，苯二氮䓬类和相关药物的使用与死亡风险增加相关。我们的结果支持治疗指南，即对于 AD 的症状治疗，非药物方法应作为一线选择。
