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Rehospitalization Risk of Receptor-Affinity Profile in Antipsychotic Drug Treatment

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Rehospitalization Risk of Receptor-Affinity Profile in Antipsychotic Drug Treatment Neuropsychiatric Disease and Treatment Dovepress open access to scientific and medical research Open Access Full Text Article ORIGINAL RESEARCH Rehospitalization Risk of Receptor-Affinity Profile in Antipsychotic Drug Treatment: A Propensity Score Matching Analysis Using a Japanese Employment-Based Health Insurance Database This article was published in the following Dove Press journal: Neuropsychiatric Disease and Treatment Yoshiteru Takekita1 Purpose: The aim of this study was to examine whether there is a difference in the risk of Sachie Inoue2 rehospitalization when antipsychotics are classified into two groups treated using drugs with Kenji Baba3 a higher or lower affinity to H1 or α1 receptors than to D2 receptors (histamine H1 receptors, Tadashi Nosaka3 adrenaline α1 receptors [HA] high- and HA low-affinity drug group, respectively) based on affinity to receptors related to sedation using a nationwide insurance claims database in Japan. 1 Department of Neuropsychiatry, Kansai Patients and Methods: We identified eligible patients by the following two criteria: (i) Medical University, Osaka, Japan; 2CRECON Medical Assessment Inc, hospitalization due to schizophrenia (International Classification of Disease [ICD]-10 code: Tokyo, Japan; 3Sumitomo Dainippon F20 or F25) in psychiatric wards between January 1st, 2005 and August 31st, 2017, and (ii) Pharma Co, Ltd, Tokyo, Japan administration of HA high- or HA low-affinity drugs in the next month after discharge from the earliest hospitalization due to schizophrenia (index month). The primary endpoint was rehospitalization due to schizophrenia. The secondary endpoints were (i) involuntary rehos­ pitalization, (ii) concomitant use of anxiolytics/hypnotics, mood stabilizers, and antiparkin­ sonian drugs, (iii) all-cause death, and (iv) medication discontinuation. Propensity score (PS) matching analysis was applied, and the hazard ratio (HR) of the event rate in the HA high- affinity drug group relative to the HA low-affinity drug group was calculated using Cox’s proportional hazards model. Results: Two thousand nine hundred and forty patients were identified as eligible patients. Among PS-matched patients (819 in each group), the HR in the HA high-affinity drug group compared with the HA low-affinity drug group was 1.018 (0.822–1.260, P = 0.870). Other outcomes did not differ significantly between the two groups. Conclusion: No significant difference was observed in the rehospitalization risk due to schizophrenia associated with HA high-affinity antipsychotic drugs. Although this study was a retrospective PS-matched cohort study, the possibility of masking of the rehospitalization risk cannot be excluded because more than 80% of the patients were administered an anxiolytic/hypnotic at the time of admission. Keywords: schizophrenia, antipsychotics, sedative effect, rehospitalization, claim database, propensity score matching Correspondence: Yoshiteru Takekita Introduction Department of Neuropsychiatry, Kansai Schizophrenia is a common disease with a lifetime prevalence of 0.7%. Its symp­ Medical University, 10-15 Fumizono-Cho, Moriguchi, Osaka 570-8506, Japan toms vary widely, including hallucination/delusion (positive symptoms), abulia/ Tel +81-6-6992-1001 autism (negative symptoms), cognitive disorders, and emotional disorders (depres­ Fax +81-6-6992-4846 1 Email [email protected] sive symptoms). The treatment goal of schizophrenia is recovery of the patient’s submit your manuscript | www.dovepress.com Neuropsychiatric Disease and Treatment 2020:16 2871–2879 2871 DovePress © 2020 Takekita et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. http://doi.org/10.2147/NDT.S276030 php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Takekita et al Dovepress social life, and medication and psychosocial interventions quetiapine-treated group. The incidence of somnolence are performed in combination for this purpose. during the 6-week double-blind RCT was 5.3% in the Antipsychotics for schizophrenia are known to have lurasidone group and 13.4% in the quetiapine group, relapse-prevention effects and suppressive effects on with greater than a two-fold difference. Although the acute symptoms, but there are multiple reports that the score of daytime drowsiness on the Epworth sleepiness rehospitalization rate of patients with schizophrenia is scale (ESS) significantly differed between the two approximately 30% in Japan.2,3 As relapse due to insuffi­ groups,13 the incidence of somnolence in the two groups cient response to antipsychotics and poor medication during the 1-year period was 3.3% and 4.7%, respectively, adherence are suggested as factors related to with no marked difference.14 Although this study also rehospitalization,4 maintaining medication adherence of suggested that the incidence of drowsiness differs among antipsychotics is considered one of the important condi­ antipsychotics, the relationship between drowsiness and tions for the prevention of relapse and minimization of rehospitalization risk remains unclear, and the design of rehospitalization risk. the sustained administration study, in which patients with As factors of poor adherence, several factors, including a high tolerance were registered, was considered to be 5 the difference in the dosage form, lack of knowledge limited for confirmation of this relationship. Although about the disease, drug abuse, negative feelings about there were many reports about the rehospitalization risk medication, and cognitive impairment, have been in schizophrenia patients, no study evaluating the relation­ 6 suggested. In addition, based on a systematic literature ship between drowsiness due to antipsychotics and the review, Velligan et al found that there are many adverse rehospitalization risk was found. Moreover, there is cur­ 6 events associated with poor adherence. According to rently no report about whether the outcome of rehospitali­ a questionnaire survey of 306 patients with schizophrenia zation differs according to the development of drowsiness 7 in Japan about adverse events due to antipsychotics, day­ due to antipsychotics or the strength of the sedative time drowsiness (50%) was the most common adverse effects. event. Of the patients, 13.7% answered that daytime drow­ The aim of this study was to evaluate whether there is siness was tolerable, and this percentage was lowest a difference in the rehospitalization risk by classifying among other common adverse events due to antipsychotics antipsychotics according to affinity to receptors related to such as weight gain (31.8%), sexual dysfunction (30.3%), sedation from the viewpoint of their pharmacological pro­ akathisia (24.0%), and dry mouth (27.0%). Afonso et al file to clarify the relationship between the development of also reported that medication adherence was poorer for the drowsiness and rehospitalization risk. Although there is no 8 outpatients with more severe somnipathy. These results clear definition for classification of each antipsychotic suggest that patients discontinue taking antipsychotics on drug according to the strength of their sedative effects, their own due to drowsiness, which may lead to the relapse we assessed our hypothesis by rating the strength of seda­ of psychiatric symptoms and rehospitalization. tive effects of antipsychotics from the viewpoint of their Differences in safety and tolerability profiles of atypi­ pharmacological profile using the ratio of affinity of dopa­ cal antipsychotics have been summarized in several review mine D2 receptors and affinity to adrenaline α1 receptors 9–11 articles. Among the atypical antipsychotics, the profile or histamine H1 receptors, which are related to the seda­ of drowsiness is different, with clozapine, olanzapine, and tive effects.15–17 Therefore, we examined whether the quetiapine summarized as very common. This adverse group of atypical antipsychotics with α1 or H1 receptor event is pharmacologically explained to be due to its high affinity had a higher risk of rehospitalization than the 10 high affinity for the H1 or α1 receptor. A comparative group with α1 and H1 receptor low affinity in patients with trial of antipsychotics with rehospitalization as an endpoint schizophrenia using the nationwide insurance claims data­ was performed during a randomized controlled sustained base in Japan. administration study (1 year)12 following a double-blind randomized controlled trial (RCT) comparing lurasidone, quetiapine, and placebo in patients with acute phase schi­ Patients and Methods zophrenia (6 weeks).13 In this study, the hazard ratios (HR) Study Design of medication discontinuation and rehospitalization were This study utilized a nationwide insurance claims database lower in the lurasidone-treated group than in the in Japan constructed by JMDC Inc.18 The JMDC database 2872 submit your manuscript | www.dovepress.com Neur opsychiatric Disease and T reatment 2020:16 DovePress Dovepress Takekita et al is an epidemiological receipt database that has accumu­ month). The exclusion
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