Antidementia drug use in Japan: Bridging the research-to-practice gap.

Abstract

In 2015, there were 47 million people with dementia worldwide.1 The overall number of people with dementia is projected to reach 132 million in 2050, 51% of whom will be from Asian countries.1 Japan has the highest prevalence of dementia among the OECD countries, where 2% of inhabitants (5 million) are living with dementia. There are significant unmet needs regarding the effectiveness of antidementia drug use in real-world settings. Populations in settings of clinical trials on antidementia drugs generally deviate from those in clinical practice settings (eg, exclusion of people aged ≥85 years).2 It remains controversial whether the desirable consequences of antidementia drug use outweigh its undesirable consequences.2 Such controversy regarding benefit-risk balance has resulted in inconsistencies in the strength of recommendations on the use of antidementia drugs among clinical practice guidelines. Some guidelines leave the choice of whether to use antidementia drugs to clinicians,3 whereas the Japanese guideline strongly recommends that clinicians use antidementia drugs in the treatment of Alzheimer's disease.4 The recommendations in guidelines might impact on the prescribing practices of antidementia drugs. Therefore, this study aimed to examine the prevalence of antidementia drug use in Japan. We used a nationwide claims database, the National Database of Health Insurance Claim Information and Specified Medical Checkups, which covers almost all claims in Japan. The database included information on clinical and procedural characteristics. The local institutional review board approved the study protocol. We identified all prescriptions for antidementia drugs (donepezil, galantamine, memantine, and rivastigmine) between April 2015 and March 2016. The number of prevalent users was counted using the patient identification numbers (called “ID0”). The annual prevalence of antidementia drug use was then calculated by dividing the number of prevalent users by the number of inhabitants. The annual quantity of antidementia drugs consumed (expressed in milligrams) was calculated for each drug, and converted into a defined daily dose. In addition, the quantity of antidementia drugs consumed was converted into a defined daily dose per 1000 inhabitants per day (DID). There were 1 733 916 prevalent users of antidementia drugs (Table 1). The annual prevalence of antidementia drug use was 1.4% among all inhabitants and 5.1% among those aged ≥65 years, with a peak of 17.0% among those aged ≥85 years. Users aged ≥85 years consumed 46.8% of the total quantity of antidementia drugs prescribed. The DID showed that 13 in 100 inhabitants aged ≥85 years received a maintenance dose of an antidementia drug every day. Similar findings were observed in both sexes. To our knowledge, this is the first study to establish the prevalence of antidementia drug use in Japan. The prevalence of antidementia drug use among inhabitants aged ≥85 years seems to be incredibly high, compared to that reported in a nationwide study in Germany which yielded an annual prevalence of 18% even among people with dementia aged ≥85 years.5 However, clinical trials of antidementia drugs have mainly focused on people with dementia aged <85 years. Our findings suggest that the significant gap between what is known and what is done needs addressing. Until more clinical trials focusing on the oldest-old population become available, the strength of recommendation on the use of antidementia drugs in guidelines will be weak or limited to the population younger than 85 years because of the serious indirectness and potentially increased risks of adverse drug reactions associated with aging. The main limitation of this study is that our database did not cover approximately 5% of inhabitants aged ≥65 years. Nevertheless, our study provides evidence on the minimum prevalence of antidementia drug use in Japan. We would like to thank Editage (www.editage.jp) for English language editing. This work was supported by a grant from the Japan Agency for Medical Research and Development (17ck0106345h0001). During the past 3 years, YO received personal fees from Merck & Co., Inc., Janssen Pharmaceuticals, Inc., Medical Technology Association, Cando Inc., and the Japan Medical Data Center. He has also received research grants from the Japan Agency for Medical Research and Development; Ministry of Health, Labour and Welfare; Japan Society for the Promotion of Science; Institute for Health Economics and Policy; and Mental Health and Morita Therapy. NS received personal fees from Daiichi Sankyo Co., Ltd., outside the submitted work.