論文 - 内田　裕之

Impact of once- versus twice-daily perphenazine dosing on clinical outcomes: An analysis of the CATIE data

Takeuchi H., Fervaha G., Uchida H., Suzuki T., Bies R., Gronte D., Remington G.

Journal of Clinical Psychiatry （Journal of Clinical Psychiatry）  75 （ 5 ） 506 - 511 2014年05月

ISSN  01606689

　概要を見る

Objective: The objective of this study was to evaluate the impact of once- versus twice-daily dosing of perphenazine, which has a plasma half-life of 8-12 hours, on clinical outcomes in patients with schizophrenia. Method: Data from phase 1 of the Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) conducted between January 2001 and December 2004 were used in this post hoc analysis. Patients with schizophrenia (DSM-IV) randomly allocated to treatment with perphenazine were also randomly assigned to once-daily (N = 133) or twice-daily (N = 124) dosing and followed over 18 months. Discontinuation rate and time to discontinuation were used as primary outcomes to compare the 2 groups. The following clinical outcomes were analyzed as secondary measures: efficacy - Positive and Negative Syndrome Scale, Clinical Global Impressions-Severity scale, Calgary Depression Scale for Schizophrenia, and Drug Attitude Inventory and safety/ tolerability - Abnormal Involuntary Movement Scale, Barnes Akathisia Rating Scale, Simpson-Angus Scale, and body weight. Data on treatment-emergent adverse events, concomitant psychotropic medications, and medication adherence (pill count and clinician rating scale) were also analyzed for each group. Results: No significant differences were found in any outcome measures between the once-daily and twice-daily dosing groups, which remained the same when using the mean dose of perphenazine as a covariate. Conclusions: Perphenazine is routinely administered in a divided dosage regimen because of its relatively short plasma half-life. However, the present findings challenge such a strategy, suggesting that once-daily represents a viable treatment option. Results are discussed in the context of more recent evidence that challenges the need for high and continuous dopamine D2 receptor blockade to sustain antipsychotic response. © Copyright 2014 Physicians Postgraduate Press, Inc.

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アジスロマイシンの高濃度希釈投与における安全性の検討　2mg/mL希釈液の末梢静脈投与

内田 裕之, 岡 秀昭, 前野 努, 三村 一行, 小野 大輔, 石井 嘉之

日本化学療法学会雑誌 （(公社)日本化学療法学会）  62 （ 3 ） 382 - 384 2014年05月

ISSN  1340-7007

　概要を見る

アジスロマイシン点滴静注用(AZM)は、静脈炎予防の観点から1mg/mLに希釈して投与しなければならない。しかし体液貯留状態の患者に対して1回500mLの輸液負荷は過剰輸液になるおそれがあり、適応が難しい現状がある。米国では2mg/mLでの投与が承認されており、希釈用輸液を制限して投与を行える可能性が考えられることから、本邦での忍容性を評価することとした。疼痛評価可能な肺炎症例を対象に、AZM500mgを250mLの希釈用輸液(5%ブドウ糖液:10例、生理食塩液:2例)を用いて2mg/mLに調製し末梢静脈から2時間かけて点滴静注した際の忍容性について評価した。AZMを12症例21回投与した。19回は忍容性良好であった。1例で投与4日目に静脈炎所見が認められたが、抜針経過観察で改善した。点滴漏れが発生した投与が1回あり、評価対象から除外した。患者危険因子および希釈用輸液の種類と忍容性に関連を認めなかった。本検討は症例数が少なく、本邦での忍容性について十分検討できていないことから2mg/mLでの画一的な投与は避け輸液負荷が問題となる症例に限り選択肢の一つとすべきと考える。(著者抄録)

Immunoreactivity of Wnt5a, Fzd2, Fzd6, and Ryk in glioblastoma: evaluative methodology for DAB chromogenic immunostaining.

Hirano H, Yonezawa H, Yunoue S, Habu M, Uchida H, Yoshioka T, Kishida S, Kishida M, Oyoshi T, Fujio S, Sugata S, Yamahata H, Hanaya R, Arita K

Brain tumor pathology 31 （ 2 ） 85 - 93 2014年04月

ISSN  1433-7398

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Predicting dopamine D<inf>2</inf> receptor occupancy following antipsychotic dose reduction: A pilot PET study

Uchida H., Bies R., Suzuki T., Graff-Guerrero A., Pollock B., Mulsant B., Mamo D.

Japanese Journal of Neuropsychopharmacology （Japanese Journal of Neuropsychopharmacology）  34 （ 2 ） 55 - 56 2014年04月

ISSN  13402544

自閉症スペクトラム障害の風景構成法の特徴　構成型の視点から

内田 裕之, 明翫 光宜, 稲生 慧, 辻井 正次

小児の精神と神経 （(一社)日本小児精神神経学会）  54 （ 1 ） 29 - 36 2014年04月

ISSN  0559-9040

　概要を見る

本研究では、自閉症スペクトラム障害(ASD)児の風景構成法の特徴を捉えるために、(1)ASD群の風景構成法の構成型の分布の特徴、(2)年齢、WISC・WAISのIQ、ベンダー得点のうち、構成型の発達に関与する要因は何かについて検討した。対象はASDの児童期・青年期男子事例49名である。ASDの構成型の分布においては、構成型IIIに大きなピークがあり、「アイテムの統合不全」がASDの風景構成法の大きな特徴であることがうかがえた。また構成型の発達には、年齢要因が大きく寄与していることが推測された。(著者抄録)

Tardive dyskinesia in relation to estimated dopamine D2 receptor occupancy in patients with schizophrenia: Analysis of the CATIE data

Yoshida K., Bies R., Suzuki T., Remington G., Pollock B., Mizuno Y., Mimura M., Uchida H.

Schizophrenia Research （Schizophrenia Research）  153 （ 1-3 ） 184 - 188 2014年03月

ISSN  09209964

　概要を見る

Objective: The objective of this study was to evaluate the relationship between antipsychotic-induced tardive dyskinesia (TD) and estimated dopamine D2 receptor occupancy levels in patients with schizophrenia, using the dataset from the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE). Methods: The dataset from 218 subjects (risperidone, N = 78; olanzapine, N = 100; ziprasidone, N = 40) who presented with a score of zero on the Abnormal Involuntary Movement Scale (AIMS) at baseline in Phase 1 of the CATIE study, and remained for ≥. 6. months, was used. Peak and trough dopamine D2 receptor occupancy levels on the day of the AIMS assessment at the endpoint were estimated from plasma antipsychotic concentrations, using population pharmacokinetic analysis and our D2 prediction model. The estimated dopamine D2 receptor occupancy levels were compared between patients who presented an AIMS score of ≥. 2 at endpoint and those with a score of zero, using the Mann-Whitney U test. Results: Estimated dopamine D2 receptor occupancy levels at trough were significantly higher in subjects who developed involuntary movements (N = 23) than those who did not (N = 195) (71.7. ±. 14.4% vs. 64.3. ±. 19.3%, p. < 0.05) while no significant difference was found in the estimated peak D2 receptor occupancy between them (75.4. ±. 8.7% vs. 72.1. ±. 9.9%, p. = 0.07). When the analyses were separately conducted for the three drugs, there were no significant differences in estimated peak or trough D2 occupancy although the values were consistently numerically higher among those developing involuntary movements. Conclusion: Greater dopamine D2 receptor blockade with antipsychotics at trough might increase the risk of tardive involuntary movements although this finding needs to be replicated in larger trials. © 2014 Elsevier B.V.

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The N-terminus and Tudor domains of Sgf29 are important for its heterochromatin boundary formation function.

Kamata K, Goswami G, Kashio S, Urano T, Nakagawa R, Uchida H, Oki M

Journal of biochemistry 155 （ 3 ） 159 - 71 2014年03月

ISSN  0021-924X

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研究と報告　日本版青年・成人感覚プロフィールの構成概念妥当性　自閉症サンプルに基づく検討

平島 太郎, 伊藤 大幸, 岩永 竜一郎, 萩原 拓, 谷 伊織, 行廣 隆次, 大西 将史, 内山 登紀夫, 小笠原 恵, 黒田 美保, 稲田 尚子, 原 幸一, 井上 雅彦, 村上 隆, 染木 史緒, 中村 和彦, 杉山 登志郎, 内田 裕之, 市川 宏伸, 辻井 正次

精神医学 （(株)医学書院）  56 （ 2 ） 123 - 132 2014年02月

ISSN  0488-1281

　概要を見る

本研究では,感覚刺激に対する反応異常のアセスメントツールとして国際的に広く用いられている感覚プロフィールの日本版の標準化に関する研究の一環として,自閉症サンプル(n=172)をもとに,日本版青年・成人感覚プロフィール(AASP-J)の妥当性を検討した。その結果,一般群とASD群との間で尺度得点に差異がみられた。また,保護者評定版の感覚プロフィールや日常生活への適応を阻害する不適応行動との関連が示され,尺度としての妥当性が確認された。ただし,知的障害やASD特性を抱える場合には,自己評定形式のAASP-Jに加え,他者評定形式の感覚プロフィールを実施し,客観的な視点から感覚異常を把握することの必要性も示唆された。(著者抄録)

[Adverse drug reactions of psychotropic agents

Miura Tomofumi, Nakanishi Shoichiro, Kanba Shigenobu, Uchida Hiroyuki, Saio Takeo, Suzuki Eiji, Suzuki Yutaro, Takahashi Keisuke, Nakagawa Atsuo, Mikuni Masahiko, Yamada Kazuo

Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica 116 （ 9 ） 735 - 745 2014年01月

ISSN  0033-2658

　概要を見る

<p>Pharmacological treatments of psychiatric illness have been developed and many psychotropic drugs are now on the market. The body of safety information regarding psychotropic agents is so large that it is difficult for clinicians to consider all the details of possible adverse drug reactions(ADRs) in daily clinical practice. Although it is impossible to predict and prevent all occurrences of ADRs, many of them may be preventable. In this context, there is a strong need for compact manuals of diagnosis and treatment for ADRs arising from psychotropic agents that are likely to be used in daily practice. Under the auspices of the Japanese Society of Psychiatry and Neurology, a task force was convened to answer this need. This review focuses on the general considerations of ADRs with psychotropic agents, based on discussions of the task force. We also discuss the guidelines for drug safety monitoring, targeted towards specific psychiatric disorders or patients taking specific classes of drugs. Finally, we introduce the Adverse Drug Reactions Relief System in Japan.</p>

Incidence of Deep Vein Thrombosis in Restrained Psychiatric Patients

Ishida T., Katagiri T., Uchida H., Takeuchi H., Sakurai H., Watanabe K., Mimura M.

Psychosomatics （Psychosomatics）  55 （ 1 ） 69 - 75 2014年01月

ISSN  0033-3182

　概要を見る

Background: Although physical restraint is still used in psychiatric inpatient settings, it sometimes causes serious side effects, including deep vein thrombosis (DVT) and resulting pulmonary embolism. Objective: The aim of this study was to investigate the incidence of the DVT in restrained patients who were receiving routine prophylaxis and to identify the risk factors of this condition. Methods: This study was conducted at Sakuragaoka Memorial Hospital, Japan from December 2008 to September 2010. Inpatients who were restrained during the study period were included. All restrained patients wore graduated compression stockings and were recommended to receive subcutaneous injection of unfractionated heparin during the period of restraint unless it was contraindicated. When plasma d-dimer level at the time of removal of restraint was ≥ 0.50. μg/dL, the patients underwent a Doppler ultrasound scanning of their lower extremities to examine the presence of DVT. A multiple logistic regression model was used to examine the effects of demographic and clinical characteristics on the incidence of DVT. Results: A total of 181 patients (98 men; mean ± standard deviation age, 47.8 ± 17.0. y) were included; DVT was detected in 21 patients (11.6%). A longer duration of restraint (odds ratio = 9.77, 95% confidence interval = 1.56-61.03, p = 0.015), excessive sedation (odds ratio = 4.90, 95% confidence interval = 1.33-18.02, p = 0.017), lower antipsychotic dosage (odds ratio = 0.05, 95% confidence interval = 0.005-0.57, p = 0.016), and recent medical hospitalization (odds ratio = 11.44, 95% confidence interval = 2.13-61.47, p = 0.004) were significantly associated with the incidence of DVT. Conclusion: The incidence of DVT in restrained psychiatric patients was not low in spite of prophylaxis. These findings emphasize the importance of regular screening of and thorough assessments of DVT, especially in restrained psychiatric patients. © 2014 The Academy of Psychosomatic Medicine.

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A review on schizophrenia and relapse - A quest for user-friendly psychopharmacotherapy

Suzuki T., Uchida H., Takeuchi H., Tsuboi T., Hirano J., Mimura M.

Human Psychopharmacology （Human Psychopharmacology）  29 （ 5 ） 414 - 426 2014年

ISSN  0885-6222

　概要を見る

Copyright © 2014 John Wiley & Sons, Ltd. Objective: Schizophrenia in general is notoriously associated with relapses rendering the illness progressive to worse outcomes, a concept of which is compatible with neurotoxicity. Therefore, relapse prevention is of utmost clinical relevance. Methods: In this review, we aim to put relapse into clinical context in the realm of natural history of, or heterogeneity in, schizophrenia and summarize risk factors of relapse. We discuss how to effectively ' define' relapse in schizophrenia and recent meta-analytic studies on this topic to highlight the importance of continuous antipsychotic treatment. Results: The following issues emerged: 'How low maintenance antipsychotic dosage could be?', 'How extended dosing could be?', 'Who could be successfully withdrawn from antipsychotics?' and 'How relapse could be defined in the first place?' The question in particular is how better to deliver antipsychotics at the lowest possible, whereby dose and dosing interval are relevant. While ongoing antipsychotic treatment is the rule, recent works are pointing to a possibility of lower dosage in the maintenance phase of the illness. Conclusions: Bearing in mind that suboptimal adherence and withdrawal from antipsychotics are an established and unequivocal risk factor for relapse, further investigations are certainly needed to explore user-friendly manner of psychopharmacotherapy to prevent relapse in schizophrenia.

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Baseline difference between patients' and clinicians' rated illness severity scores and subsequent outcomes in major depressive disorder

Tada Mitsuhiro, Uchida Hiroyuki, Suzuki Takefumi, Abe Takayuki, Pollock Bruce G., Mimura Masaru

Journal of Clinical Psychopharmacology 34 （ 3 ） 297 - 302 2014年

ISSN  0271-0749

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Critical review of antipsychotic polypharmacy in the treatment of schizophrenia

Fleischhacker W., Uchida H.

International Journal of Neuropsychopharmacology （International Journal of Neuropsychopharmacology）  17 （ 7 ） 1083 - 1093 2014年

ISSN  1461-1457

　概要を見る

Antipsychotic polypharmacy remains prevalent; it has probably increased for the treatment of schizophrenia in real-world clinical settings. The current evidence suggests some clinical benefits of antipsychotic polypharmacy, such as better symptom control with clozapine plus another antipsychotic, and a reversal of metabolic side-effects with a concomitant use of aripiprazole. On the other hand, the interpretation of findings in the literature should be made conservatively in light of the paucity of good studies and potentially serious side-effects. Also, although the available data are still limited, two smaller-scale clinical trials provide preliminary evidence that converting antipsychotic polypharmacy to monotherapy could be a valid and reasonable treatment option. Several studies have explored strategies to change physicians' antipsychotic polypharmacy prescribing behaviours. These have revealed that, while the impact of purely educational interventions may be limited, more aggressive procedures such as directly notifying physicians by letters or phone calls can be more effective in reducing antipsychotic polypharmacy. In conclusion, antipsychotic polypharmacy can work for some clinically difficult conditions; however, it should be the exception rather than the rule and may be avoidable in many patients. More importantly, the paucity of the data clearly emphasizes the need for further investigations on not only advantages and disadvantages of antipsychotic polypharmacy, but also regarding effective interventions in already prescribed polypharmacy regimens. © 2012 CINP.

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Impact of once- versus twice-daily perphenazine dosing on clinical outcomes

Takeuchi Hiroyoshi, Fervaha Gagan, Uchida Hiroyuki, Suzuki Takefumi, Bies Robert R., Gronte David, Remington Gary

Journal of Clinical Psychiatry 75 （ 5 ） 506 - 511 2014年

ISSN  0160-6689

　概要を見る

<p>Objective: The objective of this study was to evaluate the impact of once- versus twice-daily dosing of perphenazine, which has a plasma half-life of 8-12 hours, on clinical outcomes in patients with schizophrenia. Method: Data from phase 1 of the Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) conducted between January 2001 and December 2004 were used in this post hoc analysis. Patients with schizophrenia (DSM-IV) randomly allocated to treatment with perphenazine were also randomly assigned to once-daily (N = 133) or twice-daily (N = 124) dosing and followed over 18 months. Discontinuation rate and time to discontinuation were used as primary outcomes to compare the 2 groups. The following clinical outcomes were analyzed as secondary measures: efficacy - Positive and Negative Syndrome Scale, Clinical Global Impressions-Severity scale, Calgary Depression Scale for Schizophrenia, and Drug Attitude Inventory and safety/ tolerability - Abnormal Involuntary Movement Scale, Barnes Akathisia Rating Scale, Simpson-Angus Scale, and body weight. Data on treatment-emergent adverse events, concomitant psychotropic medications, and medication adherence (pill count and clinician rating scale) were also analyzed for each group. Results: No significant differences were found in any outcome measures between the once-daily and twice-daily dosing groups, which remained the same when using the mean dose of perphenazine as a covariate. Conclusions: Perphenazine is routinely administered in a divided dosage regimen because of its relatively short plasma half-life. However, the present findings challenge such a strategy, suggesting that once-daily represents a viable treatment option. Results are discussed in the context of more recent evidence that challenges the need for high and continuous dopamine D₂ receptor blockade to sustain antipsychotic response.</p>

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Japanese versions of the Executive Interview (J-EXIT25) and the Executive Clock Drawing Task (J-CLOX) for older people

Matsuoka T., Kato Y., Taniguchi S., Ogawa M., Fujimoto H., Okamura A., Shibata K., Nakamura K., Uchida H., Nakaaki S., Koumi H., Mimura M., Fukui K., Narumoto J.

International Psychogeriatrics （International Psychogeriatrics）  26 （ 8 ） 1387 - 1397 2014年

ISSN  1041-6102

　概要を見る

Background: The aim of the study was to develop the Japanese versions of Executive Interview (J-EXIT25) and Executive Clock Drawing Task (J-CLOX) and to evaluate the aspects of executive function that these two tests will be examining. Methods: The concurrent validity and reliability of J-EXIT25 and J-CLOX were first examined in all participants (n = 201). Next, the relationship between the two tests was examined using receiver operating characteristic (ROC), correlation, and regression analyses in healthy participants (n = 45) and participants with mild cognitive impairment (n = 36) and dementia (n = 95). Results: Satisfactory concurrent validity and reliability of J-EXIT25 and J-CLOX were shown. ROC analysis indicated that J-EXIT25 and J-CLOX1 were superior to the Frontal Assessment Battery, but inferior to the Mini-Mental State Examination (MMSE), in discriminating between non-dementia and dementia. J-EXIT25, J-CLOX1, and J-CLOX2 scores were significantly correlated with age, scores on the MMSE, Instrumental Activities of Daily Living (IADL) and Physical Self-Maintenance Scale (PSMS), and care level. In stepwise regression analyses of IADL scores, MMSE and J-EXIT25 were significantly independent predictors in men, and MMSE, age, and J-CLOX1 were significantly independent predictors in women. J-EXIT25, MMSE, and J-CLOX1 were significantly independent predictors in stepwise regression analysis of PSMS scores, and J-EXIT25 was the only significantly independent predictor in stepwise regression analysis of care level. Conclusions: J-EXIT25 and J-CLOX are valid and reliable instruments for assessment of executive function in older people. The present results suggest that these tests have common and distinct psychometric properties in the assessment of executive function. © International Psychogeriatric Association 2014.

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Lack of effect of risperidone or olanzapine dose reduction on metabolic parameters, prolactin, and corrected QT interval in stable patients with schizophrenia

Takeuchi Hiroyoshi, Suzuki Takefumi, Remington Gary, Watanabe Koichiro, Mimura Masaru, Uchida Hiroyuki

Journal of Clinical Psychopharmacology 34 （ 4 ） 517 - 520 2014年

ISSN  0271-0749

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Predicting dopamine D₂ receptor occupancy following antipsychotic dose reduction

Uchida Hiroyuki, Bies Robert R., Suzuki Takefumi, Graff-Guerrero Ariel, Pollock Bruce G., Mulsant Benoit H., Mamo David C.

Japanese Journal of Neuropsychopharmacology 34 （ 2 ） 55 - 56 2014年

ISSN  1340-2544

Tardive dyskinesia in relation to estimated dopamine D2 receptor occupancy in patients with schizophrenia

Yoshida Kazunari, Bies Robert R., Suzuki Takefumi, Remington Gary, Pollock Bruce G., Mizuno Yuya, Mimura Masaru, Uchida Hiroyuki

Schizophrenia Research 153 （ 1-3 ） 184 - 188 2014年

ISSN  0920-9964

　概要を見る

<p>Objective: The objective of this study was to evaluate the relationship between antipsychotic-induced tardive dyskinesia (TD) and estimated dopamine D2 receptor occupancy levels in patients with schizophrenia, using the dataset from the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE). Methods: The dataset from 218 subjects (risperidone, N = 78; olanzapine, N = 100; ziprasidone, N = 40) who presented with a score of zero on the Abnormal Involuntary Movement Scale (AIMS) at baseline in Phase 1 of the CATIE study, and remained for ≥. 6. months, was used. Peak and trough dopamine D2 receptor occupancy levels on the day of the AIMS assessment at the endpoint were estimated from plasma antipsychotic concentrations, using population pharmacokinetic analysis and our D2 prediction model. The estimated dopamine D2 receptor occupancy levels were compared between patients who presented an AIMS score of ≥. 2 at endpoint and those with a score of zero, using the Mann-Whitney U test. Results: Estimated dopamine D2 receptor occupancy levels at trough were significantly higher in subjects who developed involuntary movements (N = 23) than those who did not (N = 195) (71.7. ±. 14.4% vs. 64.3. ±. 19.3%, p. &lt; 0.05) while no significant difference was found in the estimated peak D2 receptor occupancy between them (75.4. ±. 8.7% vs. 72.1. ±. 9.9%, p. = 0.07). When the analyses were separately conducted for the three drugs, there were no significant differences in estimated peak or trough D2 occupancy although the values were consistently numerically higher among those developing involuntary movements. Conclusion: Greater dopamine D2 receptor blockade with antipsychotics at trough might increase the risk of tardive involuntary movements although this finding needs to be replicated in larger trials.</p>

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[Adverse drug reactions of psychotropic agents: adverse drug reactions and safety monitoring of psychotropic agents]

Miura T., Nakanishi S., Kanba S., Uchida H., Saio T., Suzuki E., Suzuki Y., Takahashi K., Nakagawa A., Mikuni M., Yamada K.

Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica （Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica）  116 （ 9 ） 735 - 745 2014年

ISSN  00332658

　概要を見る

Pharmacological treatments of psychiatric illness have been developed and many psychotropic drugs are now on the market. The body of safety information regarding psychotropic agents is so large that it is difficult for clinicians to consider all the details of possible adverse drug reactions(ADRs) in daily clinical practice. Although it is impossible to predict and prevent all occurrences of ADRs, many of them may be preventable. In this context, there is a strong need for compact manuals of diagnosis and treatment for ADRs arising from psychotropic agents that are likely to be used in daily practice. Under the auspices of the Japanese Society of Psychiatry and Neurology, a task force was convened to answer this need. This review focuses on the general considerations of ADRs with psychotropic agents, based on discussions of the task force. We also discuss the guidelines for drug safety monitoring, targeted towards specific psychiatric disorders or patients taking specific classes of drugs. Finally, we introduce the Adverse Drug Reactions Relief System in Japan.

Effectiveness of saikokaryukotsuboreito (herbal medicine) for antipsychotic-induced sexual dysfunction in male patients with schizophrenia: a description of two cases.

Takashi T, Uchida H, Suzuki T, Mimura M

Case reports in psychiatry 2014   784671 2014年

ISSN  2090-682X

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