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Geographical Variation in Antipsychotic Drug Use in Elderly Patients with Dementia: a Nationwide Study

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Geographical Variation in Antipsychotic Drug Use in Elderly Patients with Dementia: a Nationwide Study Journal of Alzheimer’s Disease 54 (2016) 1183–1192 1183 DOI 10.3233/JAD-160485 IOS Press Geographical Variation in Antipsychotic Drug Use in Elderly Patients with Dementia: A Nationwide Study Johanne Købstrup Zakariasa,b, Christina Jensen-Dahma, Ane Nørgaarda, Lea Stevnsborga, Christiane Gassec, Bodil Gramkow Andersend, Søren Jakobsene, Frans Boch Waldorfff , Torben Moosb and Gunhild Waldemara,∗ aDanish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark bLaboratory of Neurobiology, Biomedicine Group, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark cNational Centre for Register Based Research, Aarhus University, Aarhus, Denmark dDepartment of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark eDepartment of Geriatric Medicine, Odense University Hospital, Svendborg, Denmark f Research Unit for General Practice, Department of Public Health, University of Southern Denmark, Odense, Denmark Accepted 28 June 2016 Abstract. Background: Use of antipsychotics in elderly patients with dementia has decreased in the past decade due to safety regulations; however use is still high. Geographical variation may indicate discrepancies in clinical practice and lack of adherence to evidence-based guidelines for the management of behavioral symptoms. Objective: To investigate potential geographical variances in use of antipsychotic drugs in dementia care. Methods: A registry-based cross-sectional study in the entire elderly population of Denmark (≥65 years) conducted in 2012. Data included place of residence, prescriptions filled, and hospital discharge diagnoses. Antipsychotic drug use among elderly with (n = 34,536) and without (n = 931,203) a dementia diagnosis was compared across the five regions and 98 municipalities in Denmark, adjusted for age and sex. Results: In 2012, the national prevalence of antipsychotic drug use was 20.7% for elderly patients with dementia, with a national incidence of 3.9%. The prevalence ranged from 17.0% to 23.3% in the five regions and from 7.5% to 33.1% in the 98 municipalities, demonstrating an over four-fold difference. Conclusion: The observed geographical variation was more pronounced at municipal level as compared to regional level, suggesting that the variation may be related to variances in clinical practice in primary care. This study highlights an urgent need for further educating professional carers and physicians to guide non-pharmacological as well as pharmacological management of neuropsychiatric symptoms in elderly patients with dementia. Keywords: Antipsychotic drugs, clinical practice variation, dementia, geography, small area variation INTRODUCTION ∗Correspondence to: Gunhild Waldemar, Professor, MD, Antipsychotics are used for treatment of certain DMSc, Danish Dementia Research Centre, Department of Neu- neuropsychiatric symptoms in elderly patients with rology, Neuroscience Centre, Rigshospitalet, University of dementia, e.g., agitation, aggression, and psychotic Copenhagen, Blegdamsvej 9, #6922, 2100 Copenhagen Ø, Denmark. Tel.: +45 3545 2580; E-mail: gunhild.waldemar.01@ symptoms [1]. However, the clinical effectiveness regionh.dk. of typical and atypical antipsychotic drugs on these ISSN 1387-2877/16/$35.00 © 2016 – IOS Press and the authors. All rights reserved This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC 4.0). 1184 J.K. Zakarias et al. / Geographical Variation in Antipsychotic Use symptoms in patients with dementia is question- Thus, in order to determine possible factors con- able [2–4]. The potential modest clinical effect of tributing to the relatively high consumption of antipsychotic treatment needs to be balanced against antipsychotics in Denmark, we aimed to investigate numerous adverse events, including parkinsonian potential geographical variation. Consequently, we side effects, sedation, gait disturbance, accelerated conducted a nationwide registry-based study in the cognitive decline, pneumonia and other infections, entire elderly population of Denmark, comparing and thromboembolic events [1, 5]. Antipsychotics prevalence, incidence, and, duration of antipsychotic have also been associated with increased mortal- treatment in elderly with and without a diagnosis of ity risk [6], which has led the U.S. Food and Drug dementia in 2012 between the Danish regions and Administration and the European Medicines Agency municipalities. to issue warnings in 2005 and 2008 regarding the mortality risk associated with use of typical and atyp- ical antipsychotics in elderly patients with dementia MATERIALS AND METHODS [7, 8]. Best practice guidelines emphasize the need for initial assessment and treatment of contributing Study design and ethics medical conditions, such as infections, dehydration The study was designed as an observational cross- and pain, and non-pharmacological interventions as sectional study using data from nationwide Danish first-line approach for management of behavioral registries. symptoms in patients with dementia, although short- The study was approved by the Danish Data term treatment with antipsychotics may be warranted Protection Agency (ID no: 2007-58-0015/30-0667), in selected patients [9]. Statistics Denmark, and the Danish Health and Following the warnings, some countries launched Medicine Authority (ID no: 6-8011-907/1). All initiatives to decrease the consumption of antipsy- data were anonymized and Danish law did not chotics. As a result, the use of antipsychotics in require ethic committee approval or informed patient elderly patients with dementia decreased in the past consent. decade. The NHS England national prescribing audit showed a reduction in antipsychotic users from 17.0% in 2006 to 6.8% in 2011 in patients with Registry data sources dementia of all ages [10]. Likewise, Scotland and France demonstrated a similar decrease in use [11, All permanent residents are assigned a personal 12]. In many other countries, use is still high [13–15]. civil registration number at the time of birth or immi- In Denmark, use remains high despite a reduction gration [18], which allows for retrieval of data at an from 31.3% in 2000 to 20.4% in 2012 of antipsy- individual level in nationwide registries [17]. The chotic users with dementia ≥65 years of age [16]. National Patient Registry contains all hospitaliza- The reasons for the high consumption of antipsy- tions and invasive procedures registered since 1977 chotics in patients with dementia are unknown, but and all contacts to outpatient clinics and emergency the appropriateness of use has been questioned. departments since 1995 [19]. The Psychiatric Cen- Geographical variation in the use of antipsychotics tral Research Registry includes data on all psychiatric may indicate discrepancies in clinical practice and inpatient admissions since April 1, 1969, and outpa- lack of adherence to evidence-based guidelines for tient contacts since 1995 [20]. Information comprises the management of behavioral symptoms. Thus, dates and discharge diagnosis, registered according geographical variation unexplained by other demo- to World Health Organization’s (WHO) International graphic or medical factors may indicate a mismatch Classification of Diseases (ICD) codes. ICD-8 was between clinical practice and clinical guidelines used from 1970 to 1993 and ICD-10 from 1994 and in certain geographical areas. Danish registries are onwards. The Danish National Prescription Registry unique with respect to capturing an entire population has registered dispensed prescriptions consecutively and featuring detailed information on drug utiliza- since 1995, including prescriptions to elderly residing tion [17]. Knowledge about geographical differences in nursing homes. The drugs are registered according in the Danish population may provide further insight to the Anatomical Therapeutic Chemical (ATC) clas- into the extent and nature of variation in clinical prac- sification system, with information on amount and tice in the care of neuropsychiatric symptoms in an strength of dispensed drugs as well as dispensing international context. dates [21]. J.K. Zakarias et al. / Geographical Variation in Antipsychotic Use 1185 Demographic information DDDs prescribed in 2012 was used as a marker for treatment duration. Denmark is divided into five regions and 98 munic- ipalities. The regions are responsible for hospitals and for private practice specialists and general practition- Comorbidity ers (GPs). The municipalities are local administrative bodies responsible for public healthcare, and for pri- Comorbidity was assessed at baseline (January 1, mary care including home care and nursing homes 2012). Data from somatic and psychiatric hospital for the elderly. Information about place of residence, contacts was used to identify comorbid condi- age, gender, and marital status was retrieved from tions that could potentially influence antipsychotic the Danish Civil Registration System, while infor- drug use. The Charlson comorbidity index com- mation on living status (nursing homes) was retrieved prises 19 chronic somatic diseases and was used from Statistics Denmark. Since the municipalities are to assess comorbidity [24]. Psychiatric comorbidity subunits of the regions, each individual in the study was defined as a registered diagnosis of prior psy- population is both accounted for in the regional and chotic disorders [one of the following diagnoses:
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