研究等業績 - 原著論文 - 三島 和夫
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Efficacy of Lemborexant in Adults ≥ 65 Years of Age with Insomnia Disorder.
Valerie Arnold, Sonia Ancoli-Israel, Thien Thanh Dang-Vu, Kazuo Mishima, Kate Pinner, Manoj Malhotra, Margaret Moline
Neurology and therapy 2024年05月 [査読有り]
研究論文（学術雑誌） 国際共著
BACKGROUND: Pharmacologic treatments are available to treat insomnia, a common and burdensome sleep disorder, but may be contraindicated in older adults who are prone to side effects from sleep-promoting drugs. These analyses of sleep diary data from Study E2006-G000-303 (Study 303) investigated the benefits of lemborexant 5 mg (LEM5) and 10 mg (LEM10) in the subgroup age ≥ 65 years with insomnia. METHOD: Study 303, a 12-month, double-blind study of LEM5 and LEM10 in adults (age ≥ 18 years) with insomnia disorder (sleep onset and/or maintenance difficulties) assessed subject-reported (subjective) sleep-onset latency (sSOL), sleep efficiency (sSE), wake after sleep onset (sWASO), and total sleep time (sTST). Morning sleepiness/alertness, insomnia severity (Insomnia Severity Index [ISI]), fatigue (Fatigue Severity Scale [FSS]), perceptions of sleep-related medication effects (Patient Global Impression-Insomnia [PGI-I] questionnaire), and safety were also evaluated. RESULTS: In this subgroup of older adults (≥ 65 years; n = 262), there were significantly larger changes from baseline for sSOL, sSE, sTST, and sWASO with LEM5 and LEM10 versus placebo through month 6 (except sWASO month 1), indicating improvement; these improvements were sustained through month 12. Subject-reported increases in morning alertness were significantly greater with one or both LEM doses versus placebo through month 6 and sustained through month 12. There were significantly larger ISI total and daytime functioning score decreases (improvement) from baseline with LEM versus placebo at months 1, 3, and 6 (total score: both doses; daytime functioning: LEM5 month 1 and both doses months 3 and 6) and decreases from baseline FSS at months 1 and 3 (LEM5) and month 6 (both doses), sustained to month 12. Compared with placebo, more subjects reported that LEM (both doses) positively impacted ability to sleep, time to fall asleep, and TST through month 6, sustained to month 12, with no rebound after drug withdrawal. LEM was well tolerated to month 12; mild somnolence was the most common treatment-emergent adverse event. CONCLUSIONS: Improvements in subject-reported efficacy in LEM-treated adults age ≥ 65 years with insomnia were observed as early as the first week of treatment and sustained through end of month 12. LEM was well tolerated. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT02952820: E2006-G000-303; Study 303; SUNRISE-2 (First posted: October 2016); EudraCT 2015-001463-39 (First posted: November 2016).
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Treatment Failure and Long-Term Prescription Risk for Guideline-Recommended Hypnotics in Japan.
Masahiro Takeshima, Kazuhisa Yoshizawa, Masaya Ogasawara, Mizuki Kudo, Yu Itoh, Naoko Ayabe, Kazuo Mishima
JAMA network open 7 ( 4 ) e246865 2024年04月 [査読有り]
研究論文（学術雑誌） 国内共著
IMPORTANCE: Although insomnia guidelines recommend the use of several individual hypnotics, the most useful hypnotic for treating insomnia in a clinical setting remains unclear. OBJECTIVE: To determine which guideline-recommended hypnotics have lower risks of monotherapy failure and which hypnotics have a higher risk of long-term prescription for insomnia treatment. DESIGN, SETTING, AND PARTICIPANTS: This retrospective observational cohort study used data from the Japan Medical Data Center Claims Database from April 1, 2005, to March 31, 2021. Participants included adults whose first prescribed pharmaceutical treatment for insomnia was guideline-recommended hypnotic monotherapy. Data were analyzed from December 24, 2022, to September 26, 2023. EXPOSURES: Suvorexant, ramelteon, eszopiclone, zolpidem, and triazolam monotherapy. MAIN OUTCOMES AND MEASURES: The primary outcome was monotherapy failure, defined as a change in hypnotic or having an additional hypnotic prescribed for insomnia within 6 months of the first prescription of a guideline-recommended hypnotic monotherapy. The secondary outcome was monotherapy discontinuation, defined as no prescription of any hypnotic for 2 consecutive months within 6 months after prescribing a guideline-recommended hypnotic in patients for whom monotherapy did not fail. Monotherapy failure and discontinuation were compared using Cox proportional hazards and logistic regression models, respectively. RESULTS: The study included 239 568 adults (median age, 45 [IQR, 34-55] years; 50.2% women) whose first prescription for insomnia was guideline-recommended hypnotic monotherapy. During the 6-month follow-up period, 24 778 patients (10.3%) experienced failure of monotherapy with a guideline-recommended hypnotic. In comparison with eszopiclone, there were more cases of monotherapy failure for ramelteon (adjusted hazard ratio [AHR], 1.23 [95% CI], 1.17-1.30; P < .001), fewer cases for zolpidem (AHR, 0.84 [95% CI, 0.81-0.87]; P < .001) and triazolam (AHR, 0.82 [95% CI, 0.78-0.87]; P < .001), and no significant difference between suvorexant and eszopiclone. Among those without monotherapy failure, monotherapy was discontinued in 84.6% of patients, with more discontinuations for ramelteon (adjusted odds ratio [AOR], 1.31 [95% CI, 1.24-1.40]; P < .001) and suvorexant (AOR, 1.20 [95% CI, 1.15-1.26]; P < .001) than for eszopiclone and no significant difference between zolpidem or triazolam and eszopiclone. CONCLUSIONS AND RELEVANCE: Due to uncontrolled confounding factors in this cohort study, no conclusions regarding the pharmacologic properties of guideline-recommended hypnotics can be drawn based on these results. Further studies accounting for confounding factors, including diagnoses of chronic vs acute insomnia disorder, insomnia and psychiatric symptom severity, and physician attitudes toward hypnotic prescription, are needed.
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Impact of aripiprazole discontinuation in remitted major depressive disorder: a randomized placebo-controlled trial.
Masahiro Takeshima, Akise Umakoshi, Yuki Omori, Kazuhisa Yoshizawa, Masaya Ogasawara, Mizuki Kudo, Yu Itoh, Naoko Ayabe, Kazuo Mishima
Psychopharmacology 2024年03月 [査読有り]
研究論文（学術雑誌） 国内共著
RATIONALE: The efficacy and safety of antidepressant augmentation therapy with aripiprazole (AATA) has been established; however, the ongoing effects of continuing aripiprazole after remission remain unclear because no studies have examined this issue. OBJECTIVES: We aimed to explore the effect of AATA discontinuation on the major depressive disorder (MDD) recurrence risk in patients with remitted MDD after AATA. METHODS: This 24-week, multicenter, placebo-controlled, double-blind, randomized trial evaluated recurrence risk in patients with MDD who achieved remission with AATA. Differences in MDD recurrence, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, between the two groups were compared using survival analysis. The differences in depressive symptom severity and social functioning between the two groups were compared using a mixed model with repeated measures. Extrapyramidal symptoms and akathisia were also assessed. RESULTS: Twenty-three participants were randomized and treated. Two patients in each group experienced recurrence during the study. Kaplan-Meier analysis with Log-rank comparison showed no difference in recurrence between groups (p = 0.642). No significant difference in interactions between group and period was observed in the 17-item Hamilton depression rating scale (p = 0.492) or the Social and Occupational Functioning Assessment Scale (p = 0.638). No patients developed extrapyramidal symptoms or akathisia. CONCLUSIONS: Definitive conclusions could not be drawn owing to the small sample size. This study represents a starting point for investigating the safety of aripiprazole discontinuation on recurrence in patients with MDD who have achieved remission with AATA. Future studies with appropriate sample sizes calculated based on this study are needed.
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精神科で本当に必要な薬は何か? 精神科領域の安定確保医薬品に関する意識調査
稲垣 中, 橋本 亮太, 稲田 健, 坪井 貴嗣, 三島 和夫, 小路 純央, 齊尾 武郎, 安田 由華, 横井 優磨, 小田 陽彦, 加藤 正樹, 岸田 郁子, 岸本 泰士郎, 齊藤 卓弥, 冨田 哲, 古郡 規雄, 松尾 幸治, 渡邊 衡一郎, 木下 利彦, 三木 和平, 三野 進, 三村 將
精神神経学雑誌 ( (公社)日本精神神経学会 ) 125 ( 11 ) 932 - 943 2023年11月 [査読有り]
研究論文（学術雑誌） 国内共著
近年,医薬品の安定供給に疑念を抱かせるような事例が多発するようになったため,2020年に厚生労働省は10種類の向精神薬を含めた506種類の安定確保医薬品を指定した.しかしながら,このときには時間的な制約から精神科のステークホルダー全体のコンセンサスに基づいて10種類の向精神薬を選定できず,少数のエキスパートたちのコンセンサスに基づいて決定せざるをえなかった.今回われわれは精神科医,薬剤師,当事者・家族を対象としたweb媒体のアンケート調査を実施したうえで,第118回日本精神神経学会学術総会の際に開催されたシンポジウムにおいてデルファイ法に準じた方法により精神科のステークホルダー全体を反映したコンセンサスの形成を試みた.アンケート調査の結果,精神科医,薬剤師,当事者・家族の大半が10種類の向精神薬を安定確保医薬品に指定することを容認していることが示された.また,デルファイ法に準じた方法による意見集約の結果,リスペリドン,アリピプラゾール,オランザピン,クエチアピン,ミルタザピン,エスシタロプラム,バルプロ酸ナトリウム,炭酸リチウム,ロラゼパム,レンボレキサントの10種類の向精神薬がより妥当な安定確保医薬品として選択された.(著者抄録)
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不眠症患者におけるレンボレキサントの安全性および有効性の検討 デエビゴ錠一般使用成績調査結果報告
三島 和夫, 藤本 健一, 遠藤 亮, 石井 美佳
睡眠医療 ( (株)ライフ・サイエンス ) 17 ( 3 ) 351 - 363 2023年09月 [査読有り]
研究論文（学術雑誌） 国内共著
不眠症患者を対象にしたレンボレキサント(デエビゴ錠)の一般使用成績調査を実施し,日常診療下の安全性および有効性について539例の調査票を収集し検討を行った.本剤の製造販売承認後に同程度の規模の研究はほかになく,最初の報告となる.副作用の発現状況について検討したところ,「傾眠」の発現割合は7.65%,「悪夢」の発現割合は1.76%,「異常な夢」の発現割合は0.59%,「睡眠麻痺」の発現割合は0.20%であり,自殺念慮および自殺行動に関する副作用の発現はなかった.重篤な副作用の発現は認められなかった.有効割合は最終評価時で80.83%であった.主観的睡眠潜時の短縮,主観的総睡眠時間の延長は本剤投与8週後より認められた.本調査の結果から,安全性について検討した結果,現行の添付文書に記載された安全性プロファイルとの相違はなかった.また有効性について検討した結果,臨床上有用な薬剤であることが示された.(著者抄録)
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Development and acceptability testing of a decision aid for considering whether to reduce antipsychotics in individuals with stable schizophrenia
Aoki, Y. Takaesu, Y. Matsui, K. Tokumasu, T. Tani, H. Takekita, Y. Kanazawa, T. Kishimoto, T. Tarutani, S. Hashimoto, N. Takeuchi, H. Mishima, K. Inada, K.
Neuropsychopharmacol Rep ( Wiley ) 2023年07月 [査読有り]
研究論文（学術雑誌） 国内共著
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Feasibility of a wrist-worn wearable device for estimating mental health status in patients with mental illness.
Kazuyuki Nakagome, Manabu Makinodan, Mitsuhiro Uratani, Masaki Kato, Norio Ozaki, Seiko Miyata, Kunihiro Iwamoto, Naoki Hashimoto, Atsuhito Toyomaki, Kazuo Mishima, Masaya Ogasawara, Masahiro Takeshima, Kazumichi Minato, Toshikazu Fukami, Mari Oba, Kazuyoshi Takeda, Hideki Oi
Frontiers in psychiatry 14 1189765 - 1189765 2023年07月 [査読有り]
研究論文（学術雑誌） 国内共著
OBJECT: Real-world data from wearable devices has the potential to understand mental health status in everyday life. We aimed to investigate the feasibility of estimating mental health status using a wrist-worn wearable device (Fitbit Sense) that measures movement using a 3D accelerometer and optical pulse photoplethysmography (PPG). METHODS: Participants were 110 patients with mental illnesses from different diagnostic groups. The study was undertaken between 1 October 2020 and 31 March 2021. Participants wore a Fitbit Sense on their wrist and also completed the State-Trait Anxiety Inventory (STAI), Positive and Negative Affect Schedule (PANAS), and EuroQol 5 dimensions 5-level (EQ-5D-5L) during the study period. To determine heart rate (HR) variability (HRV), we calculated the sdnn (standard deviation of the normal-to-normal interval), coefficient of variation of R-R intervals, and mean HR separately for each sleep stage and the daytime. The association between mental health status and HR and HRV was analyzed. RESULTS: The following significant correlations were found in the wake after sleep onset stage within 3 days of mental health status assessment: sdnn, HR and STAI scores, HR and PANAS scores, HR and EQ-5D-5L scores. The association between mental health status and HR and HRV was stronger the closer the temporal distance between mental health status assessment and HR measurement. CONCLUSION: A wrist-worn wearable device that measures PPG signals was feasible for use with patients with mental illness. Resting state HR and HRV could be used as an objective assessment of mental health status within a few days of measurement.
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Clinical practice for unspecified anxiety disorder in primary care
Sakurai, H. Takeshima, M. Inada, K. Aoki, Y. Ie, K. Kise, M. Yoshida, E. Tsuboi, T. Yamada, H. Hori, H. Inada, Y. Shimizu, E. Mishima, K. Watanabe, K. Takaesu, Y.
Psychiatry and Clinical Neurosciences Reports ( Wiley ) 2 ( 3 ) 2023年06月 [査読有り]
研究論文（学術雑誌） 国内共著
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Yumi Aoki, Yoshikazu Takaesu, Ken Inada, Hiroki Yamada, Tomohiko Murao, Toshiaki Kikuchi, Masahiro Takeshima, Masayuki Tani, Kazuo Mishima, Tempei Otsubo
Frontiers in Psychiatry ( Frontiers Media SA ) 14 2023年05月 [査読有り]
研究論文（学術雑誌） 国内共著
Aim
We aimed to develop a decision aid (DA) for individuals with anxiety disorders who consider tapering benzodiazepine (BZD) anxiolytics, and if tapering, tapering BZD anxiolytics with or without cognitive behavioral therapy (CBT) for anxiety. We also assessed its acceptability among stakeholders.
Methods
First, we conducted a literature review regarding anxiety disorders to determine treatment options. We cited the results of the systematic review and meta-analysis, which we conducted previously, to describe the related outcomes of two options: tapering BZD anxiolytics with CBT and tapering BZD anxiolytics without CBT. Second, we developed a DA prototype in accordance with the International Patient Decision Aid Standards. We carried out a mixed methods survey to assess the acceptability among stakeholders including those with anxiety disorders and healthcare providers.
Results
Our DA provided information such as explanation of anxiety disorders, options of tapering or not tapering BZD anxiolytics (if tapering, the options of tapering BZD anxiolytics with or without CBT) for anxiety disorder, benefits and risks of each option, and a worksheet for value clarification. For patients (n = 21), the DA appeared to be acceptable language (86%), adequate information (81%), and well-balanced presentation (86%). The developed DA was also acceptable for healthcare providers (n = 10).
Conclusion
We successfully created a DA for individuals with anxiety disorders who consider tapering BZD anxiolytics, which was acceptable for both patients and healthcare providers. Our DA was designed to assist patients and healthcare providers to involve decision-making about whether to taper BZD anxiolytics or not. -
Yumi Aoki, Masahiro Takeshima, Takashi Tsuboi, Eiichi Katsumoto, Ken Udagawa, Ken Inada, Koichiro Watanabe, Kazuo Mishima, Yoshikazu Takaesu
International Journal of Environmental Research and Public Health ( MDPI AG ) 20 ( 7 ) 5373 - 5373 2023年04月 [査読有り]
研究論文（学術雑誌） 国内共著
Background: Although long-term use of benzodiazepines and z-drugs (BZDs) is not recommended, little is known about the stakeholders’ perceptions. This study aimed to assess and compare the perceptions of BZD use and decision making regarding its discontinuation between psychiatric outpatients and psychiatrists. Methods: A cross-sectional survey was conducted. Results: Of 104 outpatients, 92% were taking hypnotics and 96% were taking anxiolytics for ≥a year, while 49% were willing to taper hypnotic/anxiolytics within a year of starting. Most psychiatrists felt that “patient and psychiatrist make the decision together on an equal basis” compared to patients (p < 0.001), while more patients felt that “the decision is (was) made considering the psychiatrists’ opinion” compared to psychiatrists (p < 0.001). Of 543 psychiatrists, 79% reported “patients were not willing to discontinue hypnotic/anxiolytic” whereas a certain number of patients conveyed “psychiatrists did not explain in enough detail about hypnotic/anxiolytic discontinuation such as procedure (18.3%), timing (19.2%), and appropriate condition (14.4%)”. Conclusion: The results suggest that the majority of psychiatric outpatients were taking hypnotic/anxiolytics for a long time against their will. There might be a difference in perceptions toward hypnotic/anxiolytic use and decision making for its discontinuation between psychiatric outpatients and psychiatrists. Further research is necessary to fill this gap.
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Treatment Strategy for Insomnia Disorder: Japanese Expert Consensus
Yoshikazu Takaesu, Hitoshi Sakurai, Yumi Aoki, Masahiro Takeshima, Kenya Ie, Kentaro Matsui, Tomohiro Utsumi, Akiyoshi Shimura, Isa Okajima, Nozomu Kotorii, Hidehisa Yamashita, Masahiro Suzuki, Kenichi Kuriyama, Eiji Shimizu, Kazuo Mishima, Koichiro Watanabe, Ken Inada
Frontiers in Psychiatry 2023年04月 [査読有り]
研究論文（学術雑誌） 国内共著
Purpose: There is a lack of evidence regarding answers for clinical questions about treating insomnia disorder. This study aimed to answer the following clinical questions: 1) how to use each hypnotic and non-pharmacological treatment differently depending on clinical situations and 2) how to reduce or stop benzodiazepine hypnotics using alternative pharmacological and non-pharmacological treatments.
Methods: Experts were asked to evaluate treatment choices based on 10 clinical questions about insomnia disorder using a nine-point Likert scale (1=“disagree” to 9=“agree”). The responses of 196 experts were collected, and the answers were categorized into first-, second-, and third-line recommendations.
Results: The primary pharmacological treatment, lemborexant (7.3±2.0), was categorized as a first-line recommendation for sleep initiation insomnia, and lemborexant (7.3±1.8) and suvorexant (6.8±1.8) were categorized as the first-line recommendations for sleep maintenance insomnia. Regarding non-pharmacological treatments for primary treatment, sleep hygiene education was categorized as the first-line recommendation for both sleep initiation (8.4±1.1) and maintenance insomnia (8.1±1.5), while multicomponent cognitive behavioral therapy for insomnia was categorized as the second-line treatment for both sleep initiation (5.6±2.3) and maintenance insomnia (5.7±2.4). When reducing or discontinuing benzodiazepine hypnotics by switching to other medications, lemborexant (7.5±1.8) and suvorexant (6.9±1.9) were categorized as first-line recommendations.
Conclusion: Expert consensus indicates that orexin receptor antagonists and sleep hygiene education are recommended as first-line treatments in most clinical situations to treat insomnia disorder. -
Exploratory Validation of Sleep-Tracking Devices in Patients with Psychiatric Disorders.
Masaya Ogasawara, Masahiro Takeshima, Shumpei Kosaka, Aya Imanishi, Yu Itoh, Dai Fujiwara, Kazuhisa Yoshizawa, Norio Ozaki, Kazuyuki Nakagome, Kazuo Mishima
Nature and science of sleep 15 301 - 312 2023年04月 [査読有り]
研究論文（学術雑誌） 国内共著
PURPOSE: Sleep-tracking devices have performed well in recent studies that evaluated their use in healthy adults by comparing them with the gold standard sleep assessment technique, polysomnography (PSG). These devices have not been validated for use in patients with psychiatric disorders. Therefore, we tested the performance of three sleep-tracking devices against PSG in patients with psychiatric disorders. PATIENTS AND METHODS: In total, 52 patients (32 women; 48.1 ± 17.2 years, mean ± SD; 18 patients diagnosed with schizophrenia, 19 with depressive disorder, 3 with bipolar disorder, and 12 with sleep disorder cases) were tested in a sleep laboratory with PSG, along with portable electroencephalography (EEG) device (Sleepgraph), actigraphy (MTN-220/221) and consumer sleep-tracking device (Fitbit Sense). RESULTS: Epoch-by-epoch sensitivity (for sleep) and specificity (for wake), respectively, were as follows: Sleepgraph (0.95, 0.76), Fitbit Sense (0.95, 0.45) and MTN-220/221 (0.93, 0.40). Portable EEG (Sleepgraph) had the best sleep stage-tracking performance. Sleep-wake summary metrics demonstrated lower performance on poor sleep (ice, shorter total sleep time, lower sleep efficiency, longer sleep latency, longer wake after sleep onset). CONCLUSION: Devices demonstrated similar sleep-wake detecting performance as compared with previous studies that evaluated sleep in healthy adults. Consumer sleep device may exhibit poor sleep stage-tracking performance in patients with psychiatric disorders due to factors that affect the sleep determination algorithm, such as changes in autonomic nervous system activity. However, Sleepgraph, a portable EEG device, demonstrated higher performance in mental disorders than the Fitbit Sense and actigraphy.
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Management of unspecified anxiety disorder: Expert consensus.
Hitoshi Sakurai, Ken Inada, Yumi Aoki, Masahiro Takeshima, Kenya Ie, Morito Kise, Eriko Yoshida, Takashi Tsuboi, Hisashi Yamada, Hikaru Hori, Yasushi Inada, Eiji Shimizu, Kazuo Mishima, Koichiro Watanabe, Yoshikazu Takaesu
Neuropsychopharmacology reports 2023年02月 [査読有り]
研究論文（学術雑誌） 国内共著
AIMS: Treatment guidelines with respect to unspecified anxiety disorder have not been published. The aim of this study was to develop a consensus among field experts on the management of unspecified anxiety disorder. METHODS: Experts were asked to evaluate treatment choices based on eight clinical questions concerning unspecified anxiety disorder using a nine-point Likert scale (1 = "disagree" to 9 = "agree"). According to the responses from 119 experts, the choices were categorized into first-, second-, and third-line recommendations. RESULTS: Benzodiazepine anxiolytic use was not categorized as a first-line recommendation for the primary treatment of unspecified anxiety disorder, whereas multiple nonpharmacological treatment strategies, including coping strategies (7.9 ± 1.4), psychoeducation for anxiety (7.9 ± 1.4), lifestyle changes (7.8 ± 1.5), and relaxation techniques (7.4 ± 1.8), were categorized as first-line recommendations. Various treatment strategies were categorized as first-line recommendations when a benzodiazepine anxiolytic drug did not improve anxiety symptoms, that is, differential diagnosis (8.2 ± 1.4), psychoeducation for anxiety (8.0 ± 1.5), coping strategies (7.8 ± 1.5), lifestyle changes (7.8 ± 1.5), relaxation techniques (7.2 ± 1.9), and switching to selective serotonin reuptake inhibitors (SSRIs) (7.0 ± 1.8). These strategies were also highly endorsed when tapering the dosage of or discontinuing benzodiazepine anxiolytic drugs. There was no first-line recommendation regarding excusable reasons for continuing benzodiazepine anxiolytics. CONCLUSIONS: The field experts recommend that benzodiazepine anxiolytics should not be used as a first-line option for patients with unspecified anxiety disorder. Instead, several nonpharmacological interventions and switching to SSRIs were endorsed for the primary treatment of unspecified anxiety disorder and as alternatives to benzodiazepine anxiolytics.
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Physicians' attitudes toward hypnotics for insomnia;a questionnaire-based study
Masahiro Takeshima, Yoshikazu Takaesu, Yumi Aoki, Kenya Ie,Eiichi, Katsumoto, Eichi Tsuru, Takashi Tsuboi, Ken Inada, Morito Kise, Koichiro Watanabe, Kazuo Mishima
Frontiers in Psychiatry 14 1071962 - 1071962 2023年01月 [査読有り]
研究論文（学術雑誌） 国内共著
INTRODUCTION: Benzodiazepines and non-benzodiazepines are still widely prescribed despite safety concerns and the introduction of novel hypnotics (orexin receptor antagonists [ORA] and melatonin receptor agonists [MRA]), which may be influenced by physicians' attitudes toward hypnotics. METHODS: A questionnaire survey was administered to 962 physicians between October 2021 and February 2022, investigating frequently prescribed hypnotics and the reasons for their selection. RESULTS: ORA were the most frequently prescribed at 84.3%, followed by non-benzodiazepines (75.4%), MRA (57.1%), and benzodiazepines (54.3%). Compared to non-frequent prescribers of hypnotics, a logistic regression analysis showed that frequent ORA prescribers were more concerned with efficacy (odds ratio [OR]: 1.60, 95% confidence interval [CI]: 1.01-2.54, p = 0.044) and safety (OR: 4.52, 95% CI: 2.99-6.84, p < 0.001), frequent MRA prescribers were more concerned with safety (OR: 2.48, 95% CI: 1.77-3.46, p < 0.001), frequent non-benzodiazepine prescribers were more concerned with efficacy (OR: 4.19, 95% CI: 2.91-6.04, p < 0.001), and frequent benzodiazepine prescribers were more concerned with efficacy (OR: 4.19, 95% CI: 2.91-6.04, p < 0.001) but less concerned with safety (OR: 0.25, 95% CI: 0.16-0.39, p < 0.001). DISCUSSION: This study suggested that physicians believed ORA to be an effective and safe hypnotic and were compelled to prescribe benzodiazepine and non-benzodiazepine frequently, choosing efficacy over safety.
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Effects of Japanese policies and novel hypnotics on long-term prescriptions of hypnotics.
Masahiro Takeshima, Kazuhisa Yoshizawa, Minori Enomoto, Masaya Ogasawara, Mizuki Kudo, Yu Itoh, Naoko Ayabe, Yoshikazu Takaesu, Kazuo Mishima
Psychiatry and clinical neurosciences 77 ( 5 ) 264 - 272 2022年12月 [査読有り]
研究論文（学術雑誌） 国内共著
AIM: This study aimed to examine the effect of Japanese policies for appropriate hypnotics use and novel hypnotics (e.g., melatonin receptor agonist [MRA] and orexin receptor antagonist [ORA]) on long-term prescriptions of hypnotics. METHODS: This retrospective study was conducted using a large-scale health insurance claims database. Among subscribers prescribed hypnotics at least once between April 2005 and March 2021, those prescribed hypnotics for the first time after being included in the database in three periods (period 1, April 2012-March 2013; period 2, April 2016-March 2017; and period 3, April 2018-March 2019) were eligible. These were set considering the timing of the 2014 and 2018 medical fee revisions (2014 for polypharmacy of three or more hypnotics, 2018 for long-term prescription of benzodiazepine receptor agonists for >12 months). The duration of consecutive prescriptions of hypnotics over 12 months was evaluated. Factors associated with short-term prescriptions of hypnotics were also investigated. RESULTS: In total, 186,535 participants were newly prescribed hypnotics. The mean duration of prescriptions was 2.9 months, and 9.3% of participants were prescribed hypnotics for 12 months. Prescription periods were not associated with short-term prescriptions of hypnotics. ORA use was associated with short-term prescriptions of hypnotics (adjusted hazard ratio, 1.077; 95% confidence interval, 1.035-1.120; p<0.001), but MRA use was not. CONCLUSION: Japanese policies had no statistically significant effect on long-term prescriptions of hypnotics. Although this study suggests initiating ORA for insomniacs as a candidate strategy to prevent long-term prescriptions of hypnotics, further research is necessary to draw conclusions. This article is protected by copyright. All rights reserved.
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Preterm toddlers have low nighttime sleep quality and high daytime activity.
Yoko Asaka, Yusuke Mitani, Hidenobu Ohta, Takayo Nakazawa, Rika Fukutomi, Kyoko Kobayashi, Mayuko Kumagai, Hitomi Shinohara, Michiko Yoshida, Akiko Ando, Yuko Yoshimura, Machiko Nakagawa, Yoshihisa Oishi, Masato Mizushima, Hiroyuki Adachi, Yosuke Kaneshi, Keita Morioka, Yoshitaka Seto, Rinshu Shimabukuro, Michio Hirata, Takashi Ikeda, Miwa Ozawa, Masahiro Takeshima, Atsushi Manabe, Tsutomu Takahashi, Kazuo Mishima, Mitsuru Kikuchi, Hitoshi Yoda, Isao Kusakawa, Kazutoshi Cho
Scientific reports 12 ( 1 ) 20032 - 20032 2022年11月 [査読有り]
研究論文（学術雑誌） 国内共著
A number of studies have been made on the sleep characteristics of children born preterm in an attempt to develop methods to address the sleep problems commonly observed among such children. However, the reported sleep characteristics from these studies vary depending on the observation methods used, i.e., actigraphy, polysomnography and questionnaire. In the current study, to obtain reliable data on the sleep characteristics of preterm-born children, we investigated the difference in sleep properties between 97 preterm and 97 term toddlers of approximately 1.5 years of age using actigraphy. Actigraphy units were attached to the toddlers' waists with an adjustable elastic belt for 7 consecutive days, and a child sleep diary was completed by their parents. In the study, we found that preterm toddlers had more nocturnal awakenings and more daytime activity, suggesting that preterm-born children may have a different process of sleep development in their early development.
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Attitudes and Difficulties Associated with Benzodiazepine Discontinuation.
Masahiro Takeshima, Yumi Aoki, Kenya Ie, Eiichi Katsumoto, Eichi Tsuru, Takashi Tsuboi, Ken Inada, Morito Kise, Koichiro Watanabe, Kazuo Mishima, Yoshikazu Takaesu
International journal of environmental research and public health 19 ( 23 ) 2022年11月 [査読有り]
研究論文（学術雑誌） 国内共著
Long-term use of benzodiazepine receptor agonists (BZDs) may depend on clinicians' BZD discontinuation strategies. We aimed to explore differences in strategies and difficulties with BZD discontinuation between psychiatrists and non-psychiatrists and to identify factors related to difficulties with BZD discontinuation. Japanese physicians affiliated with the Japan Primary Care Association, All Japan Hospital Association, and Japanese Association of Neuro-Psychiatric Clinics were surveyed on the following items: age group, specialty (psychiatric or otherwise), preferred time to start BZD reduction after improvement in symptoms, methods used to discontinue, difficulties regarding BZD discontinuation, and reasons for the difficulties. We obtained 962 responses from physicians (390 from non-psychiatrists and 572 from psychiatrists), of which 94.0% reported difficulty discontinuing BZDs. Non-psychiatrists had more difficulty with BZD discontinuation strategies, while psychiatrists had more difficulty with symptom recurrence/relapse and withdrawal symptoms. Psychiatrists used more candidate strategies in BZD reduction than non-psychiatrists but initiated BZD discontinuation after symptom improvement. Logistic regression analysis showed that psychosocial therapy was associated with less difficulty in BZD discontinuation (odds ratio, 0.438; 95% confidence interval, 0.204-0.942; p = 0.035). Educating physicians about psychosocial therapy may alleviate physicians' difficulty in discontinuing BZDs and reduce long-term BZD prescriptions.
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Relationship between clozapine exposure and the onset of appendicitis in schizophrenia patients: a retrospective cohort study.
Yuta Kawakita, Masahiro Takeshima, Tomonari Komatsu, Aya Imanishi, Dai Fujiwara, Yu Itoh, Kazuo Mishima
BMC psychiatry 22 ( 1 ) 653 - 653 2022年10月 [査読有り]
研究論文（学術雑誌） 国内共著
OBJECTIVE: Clozapine may cause serious side effects despite benefits in patients with schizophrenia. Thus, an accurate understanding of the side-effect profile of clozapine is extremely important in the management of its administration to patients with schizophrenia. Our aim was to validate the relationship between clozapine exposure and appendicitis onset in patients with schizophrenia. METHODS: In this study, we retrospectively compared the incidence and cumulative incidence of appendicitis in patients with schizophrenia with and without a history of clozapine exposure. Among the patients with schizophrenia who visited our hospital between June 2009 and August 2021, we extracted those with a history of clozapine treatment. Patients with a history of taking clozapine were defined as the clozapine exposure group, while the others were defined as the clozapine non-exposure group. Patients with a history of appendectomy before their initial visit to our hospital or with a history of clozapine use at other hospitals were excluded. RESULTS: There were 65 patients in the clozapine exposure group and 400 patients in the clozapine non-exposure group who met the inclusion criteria. The exposure group exhibited a remarkably higher incidence of appendicitis during the observation period than the non-exposure group (863 cases vs. 124 cases per 100,000 person-years). In particular, if limited to the period of clozapine exposure, the incidence of appendicitis is extremely high, at 2,086 cases per 100,000 person-years. Moreover, multivariable analysis showed that clozapine exposure was an independent factor contributing to the onset of appendicitis. CONCLUSIONS: Clozapine exposure is associated with appendicitis onset in patients with schizophrenia.