The Incidence of Benzodiazepine and Related Drug Use in Persons with and without Alzheimer’s Disease

Article type: Research Article

Authors: Saarelainen, Laura^{a; b; *} | Taipale, Heidi^{a; b; c} | Koponen, Marjaana^{a; b} | Tanskanen, Antti^{d; e; f} | Tolppanen, Anna-Maija^{b; c} | Tiihonen, Jari^{d; f} | Hartikainen, Sirpa^{a; b}

Affiliations: [a] Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland | [b] School of Pharmacy, University of Eastern Finland, Kuopio, Finland | [c] Research Centre for Comparative Effectiveness and Patient Safety, University of Eastern Finland, Kuopio, Finland | [d] Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden | [e] Impact Assessment Unit, National Institute for Health and Welfare, Helsinki, Finland | [f] Department of Forensic Psychiatry, Niuvanniemi Hospital, Kuopio, Finland

Correspondence: [*] Correspondence to: Laura Saarelainen, MSc (Pharm), KuopioResearch Centre of Geriatric Care, School of Pharmacy, UniversityOf Eastern Finland, PO Box 1627, 70211 Kuopio, Finland.Tel.: +358 50 309 5536; Fax: +358 17 162 252; E-mail: laura.saarelainen@uef.fi

Abstract: Background:Benzodiazepines and related drugs (BZDR) are occasionally used to treat certain symptoms of Alzheimer’s disease (AD). However, the risks related to BZDR use are high in older persons. Although frequent BZDR use has been reported in persons with AD, no previous study has focused specifically on the incidence of BZDR use in this population. Objective:We investigated the incidence of BZDR use in persons with and without AD during a five-year follow-up. Methods:The Finnish nationwide, register-based MEDALZ cohort includes all AD cases who received a clinically verified AD diagnosis in 2005–2011 (n = 70,718) and their matched comparison persons. Incidence of BZDR, including benzodiazepines (lorazepam, oxazepam, temazepam, alprazolam, chlordiazepoxide, diazepam, and nitrazepam) and Z-drugs (zolpidem and zopiclone), use was investigated in the cohort from two years before to three years after the diagnosis of AD. Further, initial BZDRs were investigated. Results:The incidence of BZDR use was higher in persons with AD starting from 12 months before the diagnosis and peaked at six months after the diagnosis of AD (incidence rate ratio [IRR] = 2.6, 95% confidence interval [CI] = 2.5–2.8). Benzodiazepines were more frequently initiated by persons with AD, with the incidence peaking at six months after the diagnosis (IRR = 4.5, 95% CI = 4.1–4.9) and remaining over three times higher than in comparison persons until three years after the diagnosis. Conclusion:Early symptomatic treatment with BZDRs is contrary to AD treatment guidelines. As BZDRs impair cognition, the observed early treatment with BZDRs may complicate the monitoring of AD treatment effectiveness.

Keywords: Alzheimer’s disease, benzodiazepines, drug utilization, registries

DOI: 10.3233/JAD-150630

Journal: Journal of Alzheimer's Disease, vol. 49, no. 3, pp. 809-818, 2016