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      Current use of attention-deficit hyperactivity disorder (ADHD) medications and clinical characteristics of child and adolescent psychiatric outpatients prescribed multiple ADHD medications in Japan

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          Abstract

          Background/aim

          Patients with attention-deficit hyperactivity disorder (ADHD) manifest symptoms of hyperactivity, impulsivity, and/or inattention. ADHD medications available in Japan are limited compared with those in Western countries. Prescribing status has not been sufficiently evaluated in clinical settings in Japan. This study investigated the current use of ADHD medications and characteristics of patients who received multiple ADHD medications in a clinical setting in Japan.

          Methods

          Study participants were those who visited the Department of Child and Adolescent Psychiatry, Kohnodai Hospital between April 2015 and March 2020. We investigated patients who received osmotic-controlled release oral delivery system methylphenidate, atomoxetine, or guanfacine. A retrospective case–control design was used to evaluate the characteristics of patients who received multiple ADHD medications. Patients who were given three ADHD medications were defined as the case group. Randomly sampled sex- and age-matched patients diagnosed with ADHD were defined as the control group. We compared data for child-to-parent violence, antisocial behavior, suicide attempt or self-harm, abuse history, refusal to attend school, and two psychological rating scales (the ADHD-Rating Scale and Tokyo Autistic Behavior Scale).

          Results

          Among the 878 patients who were prescribed any ADHD medications, 43 (4.9%) received three ADHD medications. Logistic regression revealed that children with severe ADHD symptoms, autistic characteristics, or tendency of child-to-parent violence were more likely to have been prescribed three medications during their treatment.

          Conclusions

          Our findings suggest the approach to prevent the use of multiple ADHD medications. A prospective study to investigate the causality between prescribing status and clinical characteristics is warranted.

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          Most cited references34

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          Diagnostic and Statistical Manual of Mental Disorders

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            Investigation of the freely available easy-to-use software ‘EZR' for medical statistics

            Y Kanda (2012)
            Although there are many commercially available statistical software packages, only a few implement a competing risk analysis or a proportional hazards regression model with time-dependent covariates, which are necessary in studies on hematopoietic SCT. In addition, most packages are not clinician friendly, as they require that commands be written based on statistical languages. This report describes the statistical software ‘EZR' (Easy R), which is based on R and R commander. EZR enables the application of statistical functions that are frequently used in clinical studies, such as survival analyses, including competing risk analyses and the use of time-dependent covariates, receiver operating characteristics analyses, meta-analyses, sample size calculation and so on, by point-and-click access. EZR is freely available on our website (http://www.jichi.ac.jp/saitama-sct/SaitamaHP.files/statmed.html) and runs on both Windows (Microsoft Corporation, USA) and Mac OS X (Apple, USA). This report provides instructions for the installation and operation of EZR.
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              The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis

              A growing body of research identifies the harmful effects that adverse childhood experiences (ACEs; occurring during childhood or adolescence; eg, child maltreatment or exposure to domestic violence) have on health throughout life. Studies have quantified such effects for individual ACEs. However, ACEs frequently co-occur and no synthesis of findings from studies measuring the effect of multiple ACE types has been done.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Data curationRole: Methodology
                Role: Data curationRole: Methodology
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Data curationRole: InvestigationRole: Methodology
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                3 June 2021
                2021
                : 16
                : 6
                : e0252420
                Affiliations
                [1 ] Department of Psychiatry and Behavioral Science, Tokyo Medical and Dental University Graduate School, Tokyo, Japan
                [2 ] Department of Child and Adolescent Psychiatry, Kohnodai Hospital, National Center for Global Health and Medicine, Chiba, Japan
                [3 ] Department of Neuropsychiatry, Kindai University Faculty of Medicine, Osaka, Japan
                [4 ] Department of Clinical Psychology, Kohnodai Hospital, National Center for Global Health and Medicine, Chiba, Japan
                [5 ] Clinical Center of Children’s Mental Health, Kohnodai Hospital, National Center for Global Health and Medicine, Chiba, Japan
                [6 ] Department of Social Worker, Kohnodai Hospital, National Center for Global Health and Medicine, Chiba, Japan
                Chiba Daigaku, JAPAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-0816-4355
                https://orcid.org/0000-0003-3434-6280
                https://orcid.org/0000-0002-2039-8015
                Article
                PONE-D-21-04661
                10.1371/journal.pone.0252420
                8174687
                34081716
                9b1a349f-c1dc-4e03-a058-6663d80ddf3e
                © 2021 Sasaki et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 11 February 2021
                : 13 May 2021
                Page count
                Figures: 3, Tables: 3, Pages: 13
                Funding
                Funded by: Grants-in-Aid for Research from the National Center for Global Health and Medicine
                Award ID: 20A3001 and 21A1012
                Award Recipient :
                This study was supported in part by Grants-in-Aid for Research from the National Center for Global Health and Medicine (20A3001 and 21A1012). The funder played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
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                Custom metadata
                Due to ethical restrictions upon the dataset by the Ethical Committee of the National Center for Global Health and Medicine (Tokyo, Japan), the data underlying this study may not be made publicly available. The anonymized dataset is available upon request to interested and qualified researchers who meet the requirements for access to confidential data. Data access requests can be sent to the Ethical Committee of the National Center for Global Health and Medicine through the email address rinrijm@ 123456hosp.ncgm.go.jp .

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