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Benzodiazepine and related drug use increases the risk of hip fracture and death among persons with Alzheimer's disease

Persons with Alzheimer’s disease initiate benzodiazepine and related drug use more frequently than persons without the disease. This was indicated in the doctoral thesis of Laura Saarelainen, MSc (Pharm). The initiation rate was higher among persons with Alzheimer’s disease already one year before the diagnosis, and the difference between persons with and without the disease was at highest right after the diagnosis. The thesis also found that use of benzodiazepines and related drugs is associated with an increased risk of hip fractures and death among persons with Alzheimer’s disease. The association between benzodiazepine and related drug use and risk of hip fracture or death has not been previously studied among persons with Alzheimer’s disease.

Initiation of treatment with benzodiazepines and related drugs increases strongly at the time of Alzheimer’s disease diagnosis

The number of initiations of benzodiazepine and related drug use was at highest during the six months following the Alzheimer’s disease diagnosis. During this period, persons with Alzheimer’s disease were more than two times more likely to initiate benzodiazepine and related drug use than age- and gender-matched persons without the disease. The number of initiations remained higher among persons with Alzheimer’s disease for three years after the diagnosis. The increasing initiation rates of benzodiazepine and related drug use is concerning, as their use has been associated with an increased risk of falls and consequent injuries.

The risks and benefits of even short-term treatment should be carefully assessed

According to the Finnish and international treatment guidelines of cognitive disorders, benzodiazepines and related drugs can be used in short-term or infrequent treatment of the most disturbing behavioral and psychological symptoms of dementia. However, the thesis found that the associated risk of hip fracture and death were increased from the initiation of benzodiazepine and related drug use among persons with Alzheimer’s disease.

The thesis indicated that the risk of hip fracture associated with benzodiazepine and related drug use was increased by 40% among persons with Alzheimer’s disease and by 60% among those without the disease. “Previous studies have found that benzodiazepine and related drug use is a considerable risk factor for falls among older persons, and that most hip fractures result from falls. The results of this thesis highlight that the nonpharmacological treatment options should be preferred in the symptomatic treatment of, for example, insomnia, among all older persons,” Saarelainen says.

Among persons with Alzheimer’s disease, benzodiazepine and related drug use was associated with a 40% increase in the risk of death during the six-month study. This is a novel finding among persons with Alzheimer’s disease, and further research is necessary to examine the reasons for this observed association.

This thesis of Laura Saarelainen is part of a nationwide register-based MEDALZ (Medication use and Alzheimer’s disease) study performed in the University of Eastern Finland. The study included all 70,718 community-dwelling Finns who received a clinically verified diagnosis of Alzheimer’s disease during 2005–2011. These diagnoses were obtained from the nationwide Special Reimbursement Register. The study also included persons without the disease, and one to four persons without Alzheimer’s disease were matched for each person with Alzheimer’s disease based on age, gender, and region of residence. Data collected from different nationwide registers for each person included drug purchases and diagnoses of other diseases.

The doctoral dissertation of Laura Saarelainen (MSc Pharmacy) entitled Benzodiazepine and related drug use and associated adverse outcomes, The Medication Use and Alzheimer’s Disease Study will be examined at the University of Eastern Finland, at the Faculty of Health Sciences on 26 October 2018. The Opponent in the public examination will be Professor, emeritus Esa Leinonen (University of Tampere), and the Custos will be Professor Sirpa Hartikainen from the University of Eastern Finland.

Photo available for download athttps://kuvapankki.uef.fi/A/UEF+kuvahakemisto/15009?encoding=UTF-8

Saarelainen, Laura. Benzodiazepine and related drug use and associated adverse outcomes: the medication use and Alzheimer's disease study