Details of a Researcher - Uchida, Hiroyuki

Papers - Uchida, Hiroyuki

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Association between antidepressant side effects and functional impairment in patients with major depressive disorders

Kikuchi Toshiaki, Suzuki Takefumi, Uchida Hiroyuki, Watanabe Koichiro, Mimura Masaru

Psychiatry Research (Psychiatry Research) 210 ( 1 ) 127 - 133 2013.11

ISSN 0165-1781

Patients with depression may not well be aware of antidepressant adverse events (AEs); however, no studies have assessed how these AEs affect their daily function. Therefore, to evaluate the relationship between the quality of AEs and functional impairment, we studied 482 outpatients with depressive disorders who were not receiving any antidepressant treatment prior to the baseline visit and started it thereafter in usual clinical settings. The Quick Inventory for Depressive Symptomatology Self-Report Japanese version and antidepressant AEs for subjective assessment (antiAS) were performed at baseline and 10 days after antidepressant initiation (i.e. second visit). Functional impairment was evaluated with the Sheehan Disability Scale (SDS) on the second visit. As a result, the SDS was positively associated with the number of AEs (β=0.089, p=0.022) in multiple linear regression analysis (adjusted R²=0.357, p<0.001). Subjects who experienced vertigo, nausea and insomnia had significantly more functional impairment than those who did not. Additionally, the number of severe AEs (β=0.151, p<0.001) was associated with a higher SDS score, and those AEs with a negative causal attribution to antidepressants in the antiAS significantly affected the SDS (β=0.105, p=0.008). AEs of antidepressants should be carefully monitored since they could negatively affect their daily function.

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Melancholic and reactive depression

Mizushima Jin, Sakurai Hitoshi, Mizuno Yuya, Shinfuku Masaki, Tani Hideaki, Yoshida Kadunari, Ozawa Chisa, Serizawa Asako, Kodashiro Natsuko, Koide Shinya, Minamisawa Atsumi, Mutsumoto Eisaku, Nagai Nobuhiro, Noda Sachiko, Tachino Genichiro, Takahashi Tatsuichiro, Takeuchi Hiroyoshi, Kikuchi Toshiaki, Uchida Hiroyuki, Watanabe Koichiro, Kocha Hiroki, Mimura Masaru

BMC Psychiatry 13 2013.11

Background: The dominant diagnostic model of the classification of depression today is unitarian; however, since Kurt Schneider (1920) introduced the concept of endogenous depression and reactive depression, the binary model has still often been used on a clinical basis. Notwithstanding this, to our knowledge, there have been no collective data on how psychiatrists differentiate these two conditions. We therefore conducted a survey to examine how psychiatrists in Japan differentiate patients with major depressive disorder who present mainly with melancholic features and those with reactive features.Methods: Three case scenarios of melancholic and reactive depression, and one-in-between were prepared. These cases were designed to present with at least 5 symptoms listed in the DSM-IV-TR with severity being mild. We have sent the questionnaires regarding treatment options and diagnosis for those three cases on a 7-point Likert scale (1 = "not appropriate", 4 = "cannot tell", and 7 = "appropriate"). Five hundred and two psychiatrists from over one hundred hospitals and community clinics throughout Japan have participated in this survey.Results: The melancholic case resulted significantly higher than the reactive case on either antidepressants (mean ± SD: 5.9 ± 1.2 vs. 3.6 ± 1.7, p < 0.001), hypnotics (mean ± SD: 5.5 ± 1.1 vs. 5.0 ± 1.3, p < 0.001), and electroconvulsive therapy (mean ± SD: 1.5 ± 0.9 vs. 1.2 ± 0.6, p < 0.001). On the other hand, the reactive case resulted in significantly higher scores compared to the melancholic case and the one- in-between cases in regards to psychotherapy (mean ± SD: 4.9 ± 1.4 vs. 4.3 ± 1.4 vs. 4.7 ± 1.5, p < 0.001, respectively). Scores for informing patients that they suffered from "depression" were significantly higher in the melancholic case, compared to the reactive case (mean ± SD: 4.7 ± 1.7 vs. 2.2 ± 1.4, p < 0.001).Conclusions: Japanese psychiatrists distinguish between major depressive disorder with melancholic and reactive features, and thus choose different treatment strategies regarding pharmacological treatment and psychotherapy.

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Melancholic and reactive depression: A reappraisal of old categories

Mizushima J., Sakurai H., Mizuno Y., Shinfuku M., Tani H., Yoshida K., Ozawa C., Serizawa A., Kodashiro N., Koide S., Minamisawa A., Mutsumoto E., Nagai N., Noda S., Tachino G., Takahashi T., Takeuchi H., Kikuchi T., Uchida H., Watanabe K., Kocha H., Mimura M.

BMC Psychiatry (BMC Psychiatry) 13 311 2013.11

Background: The dominant diagnostic model of the classification of depression today is unitarian; however, since Kurt Schneider (1920) introduced the concept of endogenous depression and reactive depression, the binary model has still often been used on a clinical basis. Notwithstanding this, to our knowledge, there have been no collective data on how psychiatrists differentiate these two conditions. We therefore conducted a survey to examine how psychiatrists in Japan differentiate patients with major depressive disorder who present mainly with melancholic features and those with reactive features.Methods: Three case scenarios of melancholic and reactive depression, and one-in-between were prepared. These cases were designed to present with at least 5 symptoms listed in the DSM-IV-TR with severity being mild. We have sent the questionnaires regarding treatment options and diagnosis for those three cases on a 7-point Likert scale (1 = "not appropriate", 4 = "cannot tell", and 7 = "appropriate"). Five hundred and two psychiatrists from over one hundred hospitals and community clinics throughout Japan have participated in this survey.Results: The melancholic case resulted significantly higher than the reactive case on either antidepressants (mean ± SD: 5.9 ± 1.2 vs. 3.6 ± 1.7, p < 0.001), hypnotics (mean ± SD: 5.5 ± 1.1 vs. 5.0 ± 1.3, p < 0.001), and electroconvulsive therapy (mean ± SD: 1.5 ± 0.9 vs. 1.2 ± 0.6, p < 0.001). On the other hand, the reactive case resulted in significantly higher scores compared to the melancholic case and the one- in-between cases in regards to psychotherapy (mean ± SD: 4.9 ± 1.4 vs. 4.3 ± 1.4 vs. 4.7 ± 1.5, p < 0.001, respectively). Scores for informing patients that they suffered from "depression" were significantly higher in the melancholic case, compared to the reactive case (mean ± SD: 4.7 ± 1.7 vs. 2.2 ± 1.4, p < 0.001).Conclusions: Japanese psychiatrists distinguish between major depressive disorder with melancholic and reactive features, and thus choose different treatment strategies regarding pharmacological treatment and psychotherapy. © 2013 Mizushima et al.; licensee BioMed Central Ltd.

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Trajectories of individual symptoms in remitters versus non-remitters with depression

Sakurai Hitoshi, Uchida Hiroyuki, Abe Takayuki, Nakajima Shinichiro, Suzuki Takefumi, Pollock Bruce G., Sato Yuji, Mimura Masaru

Journal of Affective Disorders (Journal of Affective Disorders) 151 ( 2 ) 506 - 513 2013.11

ISSN 0165-0327

Background It remains unclear regarding the contribution of each individual symptom in predicting the outcome in major depressive disorder (MDD). The objective of this analysis was to evaluate trajectories of individual symptoms over time to identify which specific depressive item(s) could predict subsequent clinical response. Methods The data of 2874 outpatients with nonpsychotic MDD who received citalopram for up to 14 weeks in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial were analyzed. Average trajectories of individual symptoms over time were estimated for remitters and non-remitters. Moreover, specific symptoms whose improvement at week 2 predicted remission were identified, using binary logistic regression analysis. Results Trajectories were significantly different between remitters and non-remitters in all depressive symptoms. All depressive symptoms in the 16-item Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR₁₆) in the two groups, except for hypersomnia and weight change in non-remitters, substantially improved within 2 weeks and gradually continued to improve thereafter throughout the 14 weeks. Early improvements in the following five symptoms, in order of magnitude, in the QIDS-SR₁₆ were significantly associated with remission: sad mood, negative self-view, feeling slowed down, low energy, and restlessness (P<0.001, P<0.001, P=0.001, P=0.004, P=0.021). Limitations The participants were limited to the nonpsychotic MDD outpatients who received citalopram. Further, symptomatology was not evaluated at the very beginning of treatment. Conclusions While the data pertain to citalopram and replication is necessary for other antidepressants, early improvements in certain core depressive symptoms may serve as a predictor of subsequent remission.

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Effects of yoga therapy on postural stability in patients with schizophrenia-spectrum disorders

Ikai Saeko, Uchida Hiroyuki, Suzuki Takefumi, Tsunoda Kenichi, Mimura Masaru, Fujii Yasuo

Journal of Psychiatric Research 47 ( 11 ) 1744 - 1750 2013.11

ISSN 0022-3956

Introduction: Postural instability is a serious concern in patients with schizophrenia-spectrum disorders since it is expected to increase the risk of falls that may lead to fractures. The impact of yoga therapy on postural stability has not been investigated. Methods: In this eight-week single-blind randomized controlled study with an eight-week follow-up, outpatients with schizophrenia or related psychotic disorder (ICD-10) were randomly assigned to either yoga therapy or a control group. In the yoga therapy group, the subjects received weekly sessions of 60-minyoga therapy for eight weeks in addition to their ongoing treatment. In the control group, the subjects received a weekly regular day-care program. The assessments that were performed at the baseline and endpoint included the Clinical Stabilometric Platform (CSP), anteflexion in standing. Results: Forty-nine patients participated in this study (32 men; mean±SD age, 53.1±12.3 years): yoga therapy group (n=25) and control group (n=24). In the yoga group, significant improvements were observed in a total length of trunk motion, the Romberg ratio, and anteflexion in standing at week 8 (mean±SD: 63.9±40.7-53.4±26.2cm, 1.6±0.9-1.1±0.6, and-8.7±9.5 to-3.8±12.4cm, respectively) while there were no significant changes in the control group. However, those clinical gains returned to the baseline level at week 16. Conclusions: The results confirmed the beneficial effects of the yoga therapy on postural stability in patients with schizophrenia. However, the therapeutic effects seemed transient, which warrants further investigations on strategies to sustain the improvements.

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Estimated dopamine D2 receptor occupancy from plasma concentrations of atypical antipsychotics and subjective experience/drug attitude in schizophrenia

Takeuchi Hiroyoshi, Suzuki Takefumi, Bies Robert R., Remington Gary, Mamo David C., Pollock Bruce G., Mimura Masaru, Uchida Hiroyuki

Schizophrenia Research 150 ( 2-3 ) 373 - 379 2013.11

ISSN 0920-9964

Objective: The objective of this analysis was to evaluate both cross-sectional and longitudinal relationships between estimated dopamine D2 receptor occupancy from plasma concentrations of atypical antipsychotics and subjective experience/drug attitude in patients with schizophrenia. Method: The data from the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) were used in this analysis. The cross-sectional data included 371 patients receiving risperidone, olanzapine, or ziprasidone, who had completed the Drug Attitude Inventory (DAI-10) at six months and provided plasma antipsychotic concentrations. Samples were analyzed to examine the relationship between DAI-10 total scores and estimated D2 occupancy using Spearman's rank correlations, followed by multiple regression analysis. In addition, to elucidate the relationship between changes in DAI-10 scores and estimated D2 occupancy, the longitudinal data from 45 patients who experienced an increase in antipsychotic dosage between six and 12. months were analyzed. Mean peak and trough D2 occupancy levels were estimated from plasma antipsychotic concentrations using a population pharmacokinetic approach. Results: A positive association was found between estimated D2 occupancy and DAI-10 total scores in patients receiving ziprasidone in the cross-sectional dataset (rs= 0.395, P= 0.001). In contrast, a negative association was found in changes in estimated D2 occupancy and DAI-10 scores among patients receiving olanzapine in the longitudinal dataset (rs= -0.534, P= 0.010). No significant associations were found in patients receiving risperidone, or in the whole sample regarding both cross-sectional and longitudinal datasets. Conclusion: Dopamine D2 receptor occupancy may mediate subjective experience/drug attitude in patients with schizophrenia. The directionality may however differ between antipsychotics, which warrants further investigation.

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Oversight of constipation in inpatients with schizophrenia

Koizumi Teruki, Uchida Hiroyuki, Suzuki Takefumi, Sakurai Hitoshi, Tsunoda Kenichi, Nishimoto Masahiko, Ishigaki Tatsuya, Goto Akiko, Mimura Masaru

General Hospital Psychiatry 35 ( 6 ) 649 - 652 2013.11

ISSN 0163-8343

Objective: Constipation is often overlooked in patients with schizophrenia. We examined their awareness of constipation and whether they reported it to their psychiatrists. Method: Five hundred three inpatients with schizophrenia (International Classification of Diseases, 10th Revision) were interviewed about their recent bowel movements and evaluated for the diagnostic criteria for functional constipation. If constipation was present, patients were asked if they were aware of it and had reported it to their psychiatrists in charge. Additionally, their global psychopathology and functioning were assessed using the Clinical Global Impression-Schizophrenia (CGI-SCH) and the Global Assessment of Functioning (GAF), respectively. Results: The criteria for constipation were met by 184 patients (36.6%); of these patients, only 56.0% (103/184) were aware of it. Moreover, only 34 of the constipated patients (18.5%) reported its presence to their psychiatrists. No significant differences were found in the CGI-SCH overall severity or subscale scores or in the GAF scores between those patients who reported and those who failed to report constipation. Conclusions: The present study demonstrated that constipation was neither recognized nor reported to psychiatrists by a significant percentage of the patients. These findings underscore the importance of greater vigilance and active evaluation of constipation in patients with schizophrenia for appropriate clinical management.

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Effects of yoga therapy on postural stability in patients with schizophrenia-spectrum disorders: A single-blind randomized controlled trial

Ikai S., Uchida H., Suzuki T., Tsunoda K., Mimura M., Fujii Y.

Journal of Psychiatric Research (Journal of Psychiatric Research) 47 ( 11 ) 1744 - 1750 2013.11

ISSN 00223956

Introduction: Postural instability is a serious concern in patients with schizophrenia-spectrum disorders since it is expected to increase the risk of falls that may lead to fractures. The impact of yoga therapy on postural stability has not been investigated. Methods: In this eight-week single-blind randomized controlled study with an eight-week follow-up, outpatients with schizophrenia or related psychotic disorder (ICD-10) were randomly assigned to either yoga therapy or a control group. In the yoga therapy group, the subjects received weekly sessions of 60-minyoga therapy for eight weeks in addition to their ongoing treatment. In the control group, the subjects received a weekly regular day-care program. The assessments that were performed at the baseline and endpoint included the Clinical Stabilometric Platform (CSP), anteflexion in standing. Results: Forty-nine patients participated in this study (32 men; mean±SD age, 53.1±12.3 years): yoga therapy group (n=25) and control group (n=24). In the yoga group, significant improvements were observed in a total length of trunk motion, the Romberg ratio, and anteflexion in standing at week 8 (mean±SD: 63.9±40.7-53.4±26.2cm, 1.6±0.9-1.1±0.6, and-8.7±9.5 to-3.8±12.4cm, respectively) while there were no significant changes in the control group. However, those clinical gains returned to the baseline level at week 16. Conclusions: The results confirmed the beneficial effects of the yoga therapy on postural stability in patients with schizophrenia. However, the therapeutic effects seemed transient, which warrants further investigations on strategies to sustain the improvements. © 2013 Elsevier Ltd.

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Oversight of constipation in inpatients with schizophrenia: A cross-sectional study

Koizumi T., Uchida H., Suzuki T., Sakurai H., Tsunoda K., Nishimoto M., Ishigaki T., Goto A., Mimura M.

General Hospital Psychiatry (General Hospital Psychiatry) 35 ( 6 ) 649 - 652 2013.11

ISSN 01638343

Objective: Constipation is often overlooked in patients with schizophrenia. We examined their awareness of constipation and whether they reported it to their psychiatrists. Method: Five hundred three inpatients with schizophrenia (International Classification of Diseases, 10th Revision) were interviewed about their recent bowel movements and evaluated for the diagnostic criteria for functional constipation. If constipation was present, patients were asked if they were aware of it and had reported it to their psychiatrists in charge. Additionally, their global psychopathology and functioning were assessed using the Clinical Global Impression-Schizophrenia (CGI-SCH) and the Global Assessment of Functioning (GAF), respectively. Results: The criteria for constipation were met by 184 patients (36.6%); of these patients, only 56.0% (103/184) were aware of it. Moreover, only 34 of the constipated patients (18.5%) reported its presence to their psychiatrists. No significant differences were found in the CGI-SCH overall severity or subscale scores or in the GAF scores between those patients who reported and those who failed to report constipation. Conclusions: The present study demonstrated that constipation was neither recognized nor reported to psychiatrists by a significant percentage of the patients. These findings underscore the importance of greater vigilance and active evaluation of constipation in patients with schizophrenia for appropriate clinical management. © 2013 Elsevier Inc.

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Estimated dopamine D2 receptor occupancy from plasma concentrations of atypical antipsychotics and subjective experience/drug attitude in schizophrenia: An analysis of the CATIE data

Takeuchi H., Suzuki T., Bies R., Remington G., Mamo D., Pollock B., Mimura M., Uchida H.

Schizophrenia Research (Schizophrenia Research) 150 ( 2-3 ) 373 - 379 2013.11

ISSN 09209964

Objective: The objective of this analysis was to evaluate both cross-sectional and longitudinal relationships between estimated dopamine D2 receptor occupancy from plasma concentrations of atypical antipsychotics and subjective experience/drug attitude in patients with schizophrenia. Method: The data from the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) were used in this analysis. The cross-sectional data included 371 patients receiving risperidone, olanzapine, or ziprasidone, who had completed the Drug Attitude Inventory (DAI-10) at six months and provided plasma antipsychotic concentrations. Samples were analyzed to examine the relationship between DAI-10 total scores and estimated D2 occupancy using Spearman's rank correlations, followed by multiple regression analysis. In addition, to elucidate the relationship between changes in DAI-10 scores and estimated D2 occupancy, the longitudinal data from 45 patients who experienced an increase in antipsychotic dosage between six and 12. months were analyzed. Mean peak and trough D2 occupancy levels were estimated from plasma antipsychotic concentrations using a population pharmacokinetic approach. Results: A positive association was found between estimated D2 occupancy and DAI-10 total scores in patients receiving ziprasidone in the cross-sectional dataset (rs= 0.395, P= 0.001). In contrast, a negative association was found in changes in estimated D2 occupancy and DAI-10 scores among patients receiving olanzapine in the longitudinal dataset (rs= -0.534, P= 0.010). No significant associations were found in patients receiving risperidone, or in the whole sample regarding both cross-sectional and longitudinal datasets. Conclusion: Dopamine D2 receptor occupancy may mediate subjective experience/drug attitude in patients with schizophrenia. The directionality may however differ between antipsychotics, which warrants further investigation. © 2013 Elsevier B.V.

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医療・福祉機関における発達障害に関するアセスメントツールの利用実態に関する調査

松本かおり, 伊藤大幸, 小笠原恵, 明翫光宜, 染木史緒, 谷伊織, 行廣隆次, 内山登紀夫, 黒田美保, 稲田尚子, 岩永竜一郎, 萩原拓, 原幸一, 井上雅彦, 村上隆, 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) 55 ( 11 ) 1093 - 1102 2013.11

ISSN 0488-1281

発達障害児者の支援に携わる全国の2,790の医療機関および福祉機関を対象に,アセスメントツールの利用の実態と利用を規定する要因を検討することを目的に調査を行った。一般的ツールの利用率は,医療機関や児童相談所では9割,発達障害者支援センターや保健センターでは7〜8割であったが,福祉施設・事業所ではわずかに2割以下であった。全般的に知能検査・発達検査が比較的よく利用されている一方で,生活能力,問題行動,発達障害特性に関するツールは利用する機関が少なかった。特に,18歳未満の利用者がいない福祉施設・事業所では,アセスメントツールの普及が遅れていた。アセスメントツールの利用には,実施者や購入資金,実施時間といった資源の不足のみならず,アセスメントに対する理解の不足,ツールの利便性の問題なども影響することが推測された。(著者抄録)

Antipsychotic polypharmacy

Kishimoto Taishiro, Watanabe Koichiro, Uchida Hiroyuki, Mimura Masaru, Kane John M., Correll Christoph U.

Psychiatry Research 209 ( 3 ) 406 - 411 2013.10

ISSN 0165-1781

While combining antipsychotics is common in schizophrenia treatment, the literature on the reasons for antipsychotic polypharmacy (APP) is limited. We aimed to identify prescriber attitudes and rationales for APP in Japan where high APP utilization is reported. Two-hundred and seventeen psychiatrists participated in the survey, which assessed APP attitudes and behaviors. Prescribing APP to 47.7±24.7% (mean±S.D.) of their patients, psychiatrists reported that they were "moderately" concerned about APP. The most APP-justifiable factors were (1="not at all" to 5="extreme") cross titration (4.50±0.67), randomized controlled evidence (3.67±0.83), and treatment of comorbid conditions (3.31±0.83). Conversely, APP-discouraging factors were chronic side effects (4.14±0.64), difficulty determining cause and effect (4.07±0.74), and acute side effects (3.99±0.81). Comparing high to low APP prescribers (>50% vs. ≤50% of patients), no differences emerged regarding APP justification and concerns. In multivariate analyses, high APP use was associated with practice at a psychiatric hospital (OR: 2.70, 95% CI: 1.29-5.67, p=0.009), concern about potential drug-drug interactions (OR: 1.56, 95% CI: 1.04-2.35, p=0.031), and less reliance on case reports of APP showing efficacy (OR: 0.64, 95% CI: 0.44-0.92, p=0.017) (r²=0.111, p=0.001). High and low APP prescribers shared a comparable degree of justifications and concerns. Future research should examine the impact of cultural determinants on APP.

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Antipsychotic polypharmacy: A Japanese survey of prescribers' attitudes and rationales

Kishimoto T., Watanabe K., Uchida H., Mimura M., Kane J.M., Correll C.U.

Psychiatry Research (Psychiatry Research) 209 ( 3 ) 406 - 411 2013.10

ISSN 01651781

While combining antipsychotics is common in schizophrenia treatment, the literature on the reasons for antipsychotic polypharmacy (APP) is limited. We aimed to identify prescriber attitudes and rationales for APP in Japan where high APP utilization is reported. Two-hundred and seventeen psychiatrists participated in the survey, which assessed APP attitudes and behaviors. Prescribing APP to 47.7±24.7% (mean±S.D.) of their patients, psychiatrists reported that they were "moderately" concerned about APP. The most APP-justifiable factors were (1="not at all" to 5="extreme") cross titration (4.50±0.67), randomized controlled evidence (3.67±0.83), and treatment of comorbid conditions (3.31±0.83). Conversely, APP-discouraging factors were chronic side effects (4.14±0.64), difficulty determining cause and effect (4.07±0.74), and acute side effects (3.99±0.81). Comparing high to low APP prescribers (>50% vs. ≤50% of patients), no differences emerged regarding APP justification and concerns. In multivariate analyses, high APP use was associated with practice at a psychiatric hospital (OR: 2.70, 95% CI: 1.29-5.67, p=0.009), concern about potential drug-drug interactions (OR: 1.56, 95% CI: 1.04-2.35, p=0.031), and less reliance on case reports of APP showing efficacy (OR: 0.64, 95% CI: 0.44-0.92, p=0.017) (r2=0.111, p=0.001). High and low APP prescribers shared a comparable degree of justifications and concerns. Future research should examine the impact of cultural determinants on APP. © 2013 Elsevier Ireland Ltd.

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An open-label study of algorithm-based treatment versus treatment-as-usual for patients with schizophrenia

Hirano Jinichi, Watanabe Koichiro, Suzuki Takefumi, Uchida Hiroyuki, Den Ryosuke, Kishimoto Taishiro, Nagasawa Takashi, Tomita Yusuke, Hara Koichiro, Ochi Hiromi, Kobayashi Yoshimi, Ishii Mutsuko, Fujita Akane, Kanai Yoshihiko, Goto Megumi, Hayashi Hiromi, Inamura Kanako, Ooshima Fumiko, Sumida Mariko, Ozawa Tomoko, Sekigawa Kayoko, Nagaoka Maki, Yoshimura Kae, Konishi Mika, Inagaki Ataru, Saito Takuya, Motohashi Nobutaka, Mimura Masaru, Okubo Yoshiro, Kato Motoichiro

Neuropsychiatric Disease and Treatment (Neuropsychiatric Disease and Treatment) 9 1553 - 1564 2013.10

ISSN 1176-6328

Objective: The use of an algorithm may facilitate measurement-based treatment and result in more rational therapy. We conducted a 1-year, open-label study to compare various outcomes of algorithm-based treatment (ALGO) for schizophrenia versus treatment-as-usual (TAU), for which evidence has been very scarce. Methods: In ALGO, patients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) were treated with an algorithm consisting of a series of antipsychotic monotherapies that was guided by the total scores in the positive and negative syndrome scale (PANSS). When posttreatment PANSS total scores were above 70% of those at baseline in the first and second stages, or above 80% in the 3rd stage, patients proceeded to the next treatment stage with different antipsychotics. In contrast, TAU represented the best clinical judgment by treating psychiatrists. Results: Forty-two patients (21 females, 39.0 10.9 years-old) participated in this study. The baseline PANSS total score indicated the presence of severe psychopathology and was significantly higher in the ALGO group (n=25; 106.9 ± 20.0) than in the TAU group (n = 17; 92.2 ± 18.3) (P = 0.021). As a result of treatment, there were no significant differences in the PANSS reduction rates, premature attrition rates, as well as in a variety of other clinical measures between the groups. Despite an effort to make each group unique in pharmacologic treatment, it was found that pharmacotherapy in the TAU group eventually became similar in quality to that of the ALGO group. Conclusion: While the results need to be carefully interpreted in light of a hard-to-distinguish treatment manner between the two groups and more studies are necessary, algorithm-based antipsychotic treatments for schizophrenia compared well to treatment-as-usual in this study.

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Estimated dopamine D2 receptor occupancy and remission in schizophrenia

Moriguchi Sho, Bies Robert R., Remington Gary, Suzuki Takefumi, Mamo David C., Watanabe Koichiro, Mimura Masaru, Pollock Bruce G., Uchida Hiroyuki

Journal of Clinical Psychopharmacology 33 ( 5 ) 682 - 685 2013.10

ISSN 0271-0749

In treating schizophrenia, 65% to 80% occupancy of dopamine D2 receptors optimizes therapeutic efficacy while minimizing risks of extrapyramidal symptoms and cognitive impairments. However, it is unclear as to whether it is necessary to keep D2 receptor occupancy within this therapeutic window to maintain clinical response. The data set from phase 1 of the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) trial was reappraised. Thirty patients receiving risperidone (12 patients), olanzapine (12 patients), or ziprasidone (6 patients) fulfilled the following definition of remission and were included: a score of 3 or less on the 8 specific items in the Positive and Negative Syndrome Scale (ie, P1, P2, P3, N1, N4, N6, G5, and G9; adopted from Andreasen et al, 2005) at the initial assessment and months 1, 2, and 6. Peak and trough D2 receptor occupancy levels at month 6 were estimated from plasma antipsychotic concentrations using population pharmacokinetic analysis and our D2 prediction model. Estimated mean ± SD peak and trough D2 receptor occupancy levels at month 6 were 70.3% ± 9.8% and 60.5% ± 20.2%, respectively; among these individuals, 46.7% (14 patients) did not achieve continuous blockade of 65% or greater (ie, trough D2 occupancy of <65%). In conclusion, approximately half of patients with remission did not achieve continuous blockade of estimated D2 receptor occupancy 5% or greater. These results extend our previous findings and suggest that sustained D2 receptor occupancy greater than 65% may not always be necessary for the maintenance treatment of schizophrenia.

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Estimated dopamine D2 receptor occupancy and remission in schizophrenia: Analysis of the catie data

Moriguchi S., Bies R., Remington G., Suzuki T., Mamo D., Watanabe K., Mimura M., Pollock B., Uchida H.

Journal of Clinical Psychopharmacology (Journal of Clinical Psychopharmacology) 33 ( 5 ) 682 - 685 2013.10

ISSN 02710749

In treating schizophrenia, 65% to 80% occupancy of dopamine D2 receptors optimizes therapeutic efficacy while minimizing risks of extrapyramidal symptoms and cognitive impairments. However, it is unclear as to whether it is necessary to keep D2 receptor occupancy within this therapeutic window to maintain clinical response. The data set from phase 1 of the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) trial was reappraised. Thirty patients receiving risperidone (12 patients), olanzapine (12 patients), or ziprasidone (6 patients) fulfilled the following definition of remission and were included: a score of 3 or less on the 8 specific items in the Positive and Negative Syndrome Scale (ie, P1, P2, P3, N1, N4, N6, G5, and G9; adopted from Andreasen et al, 2005) at the initial assessment and months 1, 2, and 6. Peak and trough D2 receptor occupancy levels at month 6 were estimated from plasma antipsychotic concentrations using population pharmacokinetic analysis and our D2 prediction model. Estimated mean ± SD peak and trough D2 receptor occupancy levels at month 6 were 70.3% ± 9.8% and 60.5% ± 20.2%, respectively; among these individuals, 46.7% (14 patients) did not achieve continuous blockade of 65% or greater (ie, trough D2 occupancy of <65%). In conclusion, approximately half of patients with remission did not achieve continuous blockade of estimated D2 receptor occupancy 5% or greater. These results extend our previous findings and suggest that sustained D2 receptor occupancy greater than 65% may not always be necessary for the maintenance treatment of schizophrenia.

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日本版Vineland-II適応行動尺度の開発　適応行動尺度の項目分析と年齢による推移

谷伊織, 伊藤大幸, 行廣隆次, 平島太郎, 安永和央, 内山登紀夫, 小笠原恵, 黒田美保, 稲田尚子, 萩原拓, 原幸一, 岩永竜一郎, 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, 田中恭子, 辻井正次

精神医学 ((株)医学書院) 55 ( 10 ) 971 - 980 2013.10

ISSN 0488-1281

本研究は,全年齢に適用可能であり国際的に広く利用されるVineland Adaptive Behavior Scales, Second Editionの日本版の標準化に関する研究の一環として,適応行動尺度の項目分析と年齢による推移を検討した。項目分析の結果,いずれの項目も十分な項目-合計相関を示した。さらに,IRT(item response theory)によって項目の再配置を行い,打ち切りルールを適用し,尺度得点を求めた。打ち切り前後の得点の相関を検討したところ,いずれの下位尺度についても.99程度の強い相関がみられた。Vineland-II日本版の適応尺度の年齢推移を調べた結果,いずれの尺度も全年代の発達に対応していることが明らかになった。これらの結果は適応行動尺度の高い信頼性・妥当性を示している。(著者抄録)

Ten year outcomes of outpatients with schizophrenia on conventional depot antipsychotics

Uchida Takahito, Suzuki Takefumi, Sakurai Hitoshi, Tsutsumi Chisa, Den Ryosuke, Mimura Masaru, Uchida Hiroyuki

International Clinical Psychopharmacology 28 ( 5 ) 261 - 266 2013.09

ISSN 0268-1315

Long-term follow-up data of patients with schizophrenia on depot antipsychotics have been few and the longest follow-up period has been up to 7 years. We carried out a systematic chart review to examine 10-year outcomes for outpatients with schizophrenia who were receiving a conventional depot antipsychotic. Maintenance of outpatient status for 10 years was considered as a favorable outcome. From the initial sample of 1587 outpatients, 90 patients who were receiving a depot antipsychotic were included in this study (mean±SD, age 44.0±13.0 years; men, N=54). Haloperidol decanoate, fluphenazine decanoate, fluphenazine enanthate, and haloperidol decanoate plus fluphenazine enanthate were used in 53 (58.9%), 29 (32.2%), seven (7.8%), and one (1.1%) patients, respectively. These depot antipsychotics accounted for 36.9% of the total antipsychotic dosage on average. Seventeen patients (18.9%) successfully maintained outpatient status for 10 years. The most frequent reason for dropout was 'hospitalization' (N=49, 54.4%), followed by 'referral to another clinic/hospital' (N=9, 10.0%) and 'side effects' (N=7, 7.8%). As only 36.9% of the chlorpromazine equivalents were administered through depot antipsychotics, it is difficult to draw any firm conclusion. Still, the data suggest that even depot antipsychotics may not sufficiently prevent relapse in the treatment of schizophrenia.

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Absence of evidence that the pro re nata regimen confers benefit

Yoshida Kazunari, Suzuki Takefumi, Uchida Hiroyuki, Mimura Masaru

International Clinical Psychopharmacology 28 ( 5 ) 228 - 237 2013.09

ISSN 0268-1315

Studies were sought that evaluated the prevalence, effectiveness, and safety of pro re nata (p.r.n.) medications in psychiatric practice for which evidence has been scarce despite their wide application. To this end, a systematic literature search was performed using various search engines (last search: October 2012) with cross-referencing. A total of 34 studies were identified: 16 studies on epidemiological usage, 16 retrospective studies on effectiveness/safety as well as reasons, and only two prospective studies on the effectiveness/safety of p.r.n. medications. All the patients studied were inpatients, and the reasons for p.r.n. were acute behavioral dyscontrol in 29 studies. Psychiatric diagnoses and outcome measures to assess effectiveness/safety varied and were described in 27 and 20 studies, respectively. Medications under study included antipsychotics (mainly chlorpromazine, haloperidol, olanzapine, risperidone, or quetiapine), benzodiazepines (mainly diazepam and lorazepam), and antihistamines (mainly diphenhydramine). Altogether, 17 studies reported that p.r.n. medications were effective in psychiatric inpatients. Those two prospective studies targeted solely a child/adolescent population with small sample sizes. Currently available data are limited in number, quality, and scope; there has been only equivocal evidence to guide the choice of p.r.n. medications for psychiatric patients, hence there is a need for more investigations on this important clinical topic.

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Effects of risperidone and olanzapine dose reduction on cognitive function in stable patients with schizophrenia

Takeuchi Hiroyoshi, Suzuki Takefumi, Remington Gary, Bies Robert R., Abe Takayuki, Graff-Guerrero Ariel, Watanabe Koichiro, Mimura Masaru, Uchida Hiroyuki

Schizophrenia Bulletin 39 ( 5 ) 993 - 998 2013.09

ISSN 0586-7614

Impact of dose reduction of atypical antipsychotics on cognitive function has not been investigated in stable patients with schizophrenia. In this open-label, 28-week, randomized controlled trial, stable patients with schizophrenia treated with risperidone or olanzapine were randomly assigned to the reduction group (dose reduced by 50% in 4 weeks and then maintained) or maintenance group (dose kept constant). Assessments at baseline and week 28 included the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Positive and Negative Syndrome Scale (PANSS), and Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). Sixty-one patients were enrolled; 2 of 31 (6.5%) and 5 of 30 (16.7%) patients prematurely withdrew from the study in the reduction and maintenance groups, respectively. While no significant differences in change in the PANSS total score were observed between the 2 groups, the reduction group showed significantly greater improvements in the RBANS and DIEPSS total scores compared with the maintenance group (mean ± SD, +7.0±7.1 vs -0.1±8.0, P <. 001; -0.9±1.7 vs +0.1±1.2, P =. 010, respectively). This 6-month pilot study suggests that risperidone or olanzapine dose reduction of 50% can improve cognitive function for stable patients with schizophrenia. Due to the open-label design, small sample size, and short study duration, however, there is a need to confirm the finding through double-blind, larger scale trials with longer follow-up periods. Moreover, potential risks of relapse following antipsychotic dose reduction should be thoroughly investigated in longer term studies.

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