Psychotropic drugs use and psychotropic polypharmacy among persons with Alzheimer's disease
Introduction
Alzheimer's disease (AD) is a neurodegenerative disease and the most common cause of dementia. AD is characterized by a decline in memory, language, problem solving and other cognitive skills that affects a person's ability to perform in activities in daily life (Alzheimer's Association, 2016).
Behavioural and Psychological Symptoms of Dementia (BPSD) are experienced by up to 97% of persons with dementia over a five-year period (Steinberg et al., 2008). Psychotropic drugs are frequently used to treat BPSD even though the evidence for benefits of their use is limited (Wolf et al., 2016; White et al., 2017). Concerns have been raised about the safety of psychotropic drugs in older persons and persons with dementia (Chahine et al., 2010, Johnell et al., 2017), because they are associated with an increased risk of injurious falls (Zdanys et al., 2016, Johnell et al., 2017), hip fractures (Saarelainen et al., 2017; Torvinen-Kiiskinen et al., 2017, Koponen et al., 2017a), stroke (Trifirò et al., 2010, Mittal et al., 2011, Taipale et al., 2017), hospitalization (Johnell et al., 2017), and mortality (Huybrechts et al., 2011, Maust et al., 2015, Koponen et al., 2017b). In addition, the use of benzodiazepines and antipsychotics may also be associated with cognitive decline and dementia (Billiote de Gage et al., 2012; Shash et al., 2016; Wolf et al., 2016).
Psychotropic polypharmacy (PPP), the use of two or more psychotropic drugs concomitantly, generally is not recommended for older persons with dementia and should be avoided (Zdanys et al., al.,2016; Finnish Medical Society Duodecim, 2017). PPP is also associated with an increased risk of injurious falls, hospitalization and mortality (Johnell et al., 2017, Koponen et al., 2017b).
In previous observational studies on PPP, prevalence varied between 14% and 50% in persons with dementia (Nijk et al., 2009, Gustafsson et al., 2013, Vasudev et al., 2015, Walsh et al., 2016, Breining et al., 2016, Nørgaard et al., 2017). These studies were conducted in different settings (including nursing home residents) and countries, some including a limited sample size, and thus, more studies are needed in representative populations. To our knowledge, no previous studies have focused on assessing the prevalence and predictors of PPP before and after the diagnosis of AD. As psychotropic drugs may be used for treatment of behavioral and psychological symptoms of dementia treatment patterns may change when person has received AD diagnosis. On the other hand, older persons in general and persons with AD are susceptible to adverse effects of psychotropic drugs and thus, these drugs should be used with caution. The aim of this research was to determine the prevalence of psychotropic drug use and PPP among persons with Alzheimer's disease and investigate the predictors for concomitant use of two or more psychotropic drugs.
Section snippets
Experimental procedures
This study is part of the large nationwide Medication use and Alzheimer's disease (MEDALZ) study and data from this study was utilized. The MEDALZ study has been described in detail elsewhere (Tolppanen et al., 2016). In brief, this cohort included all community-dwelling persons who received their first clinically verified AD diagnosis between 2005 and 2011 in Finland (n = 70,719). Cohort members were identified from the Special Reimbursement register maintained by the Social Insurance
Study population
The mean follow-up time was 3.4 years (SD 1.05) for the AD cohort after AD diagnosis and 3.6 years (SD 0.91) for the matched cohort after the index date. During the follow-up, 38,318 (27.1%) persons died (n = 24,251, 34.3% in AD cohort and n = 14,067, 19.9% in the matched cohort). History of any psychiatric disorder was present in 4.5% of persons with AD and in 3.8% of persons without AD (ORunadjusted = 1.20; 95% CI = 1.14–1.26). Persons with AD were more likely to have diabetes, epilepsy, any
Discussion
To our knowledge, this is the first study reporting psychotropic polypharmacy among community-dwelling persons with AD over a nine year period. We found an increasing prevalence of psychotropic drug use and PPP from five years before until four years after AD diagnosis. Four years after the index date almost half of the persons with AD used some psychotropic drug and almost one fifth used two or more psychotropic drugs. The high prevalence found for psychotropic drug use and PPP is concerning,
Role of funding source
No funding was received for this study.
Contributors
HT and SH planned the research project. HT, AMT, AT and KO collected data. KO and HT performed statistical analyses and act as guarantor. KO, HT and SH drafted the first version of the manuscript, and all authors revised the draft version and accepted the final manuscript.
Conflict of interest
HT, JT and AT have participated in research projects funded by Janssen and Eli Lilly with grants paid to the institution where they were employed. AT is a member of advisory board of Janssen. JT reports serving as a consultant to AstraZeneca, Bristol-Myers Squibb, Eli Lilly, F. Hoffman-La Roche, Janssen-Cilag, Lundbeck, and Organon. He has received fees for giving expert opinions to AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Otsuka and Pfizer, and
Acknowledgments
None.
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