Details of a Researcher - Uchida, Hiroyuki

Papers - Uchida, Hiroyuki

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Factors associated with response to clozapine in schizophrenia: A review

Suzuki T., Uchida H., Watanabe K., Kashima H.

Psychopharmacology Bulletin (Psychopharmacology Bulletin) 44 ( 1 ) 32 - 60 2011.11

ISSN 00485764

Background: Clozapine has been serving as the gold standard medication for patients with treatment-resistant schizophrenia who failed to respond to other antipsychotics. However, factors affecting response to this medication have not been comprehensively reviewed recently. Methods: In order to find factors associated with response to clozapine in schizophrenia, a literature search was conducted using PubMed through January 2011 with keywords of clozapine, response, and schizophrenia. Cross-referencing of relevant articles was also performed. Factors were arbitrarily classified into the following: demographic/clinical, oral dosage/pharmacokinetic, biochemical, (electro)physiological, genetic, imaging, and combinations. Results: A synthesis from 280 articles indicated that demographic and clinical variables such as high baseline symptoms and low premorbid functioning have not been particularly useful in predicting response to clozapine. Pharmacokinetic evidence points to a threshold clozapine level of 350 ng/ml but in a context of significant inter- as well as intra-individual variability. Pharmacokinetic perspectives appear to have more implication in special situations including poor response, suspected toxicity and nonadherence. A number of laboratory-based studies have reported on many potential candidates for response prediction to clozapine, however, reproducibility, specificity, robustness of the findings, as well as clinical feasibility and cost-effectiveness all pose a significant practical challenge, in relation with the fact that pathophysiological bases of treatment resistance in schizophrenia largely remain to be elucidated. Conclusions: No unequivocal factors to clozapine response were found despite a relatively rich body of the literature, which calls for more works on this important topic. Clozapine level of 350 ng/ml appears to be useful in case of nonresponse.

Time course of improvement with antipsychotic medication in treatment-resistant schizophrenia

Suzuki Takefumi, Remington Gary, Arenovich Tamara, Uchida Hiroyuki, Agid Ofer, Graff-Guerrero Ariel, Mamo David C.

British Journal of Psychiatry (British Journal of Psychiatry) 199 ( 4 ) 275 - 280 2011.10

ISSN 0007-1250

Background: Improvements are greatest in the earlier weeks of antipsychotic treatment of patients with non-resistant schizophrenia. Aims: To address the early time-line for improvement with antipsychotics in treatment-resistant schizophrenia. Method: Randomised double-blind trials of antipsychotic medication in adult patients with treatment-resistant schizophrenia were investigated (last search June 2010). A series of metaregression analyses were carried out to examine the effect of time on the average item scores in the Positive and Negative Syndrome Scale (PANSS) or Brief Psychiatric Rating Scale (BPRS) at three or more distinct time points within the first 6 weeks of treatment. Results: Study duration varied from 4 weeks to 1 year and the definitions of treatment resistance as well as of treatment response were not necessarily consistent across 19 identified studies, resulting in highly variable rates of response (0-76%). The mean standardised baseline item score in the PANSS or BPRS was 3.4 (s.e. = 0.06) in the five studies included in the meta-regression analysis, with the average baseline Clinical Global Impression - Severity score being 5.2 (marked illness). For the pooled population treated with a range of antipsychotics (n = 1019), significant reductions in the mean item scores occurred during the first 4 weeks; improvements observed in later weeks were smaller and non-significant. In contrast, weekly improvement with clozapine was significant throughout (n = 356). Conclusions: Our findings provide preliminary evidence that the majority of improvement with antipsychotics may occur relatively early. More consistent improvements with clozapine may be associated with a gradual titration. To further elucidate response patterns, future studies are needed to provide data over regular intervals during earlier stages of treatment.

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Role of sonic hedgehog signaling in migration of cell lines established from CD133-positive malignant glioma cells.

Uchida H, Arita K, Yunoue S, Yonezawa H, Shinsato Y, Kawano H, Hirano H, Hanaya R, Tokimura H

Journal of neuro-oncology 104 ( 3 ) 697 - 704 2011.09

ISSN 0167-594X

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Species-specific functional evolution of neuroglobin.

Wakasugi K, Takahashi N, Uchida H, Watanabe S

Marine genomics 4 ( 3 ) 137 - 42 2011.09

ISSN 1874-7787

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The evolution of antipsychotic switch and polypharmacy in natural practice - A longitudinal perspective

Tsutsumi Chisa, Uchida Hiroyuki, Suzuki Takefumi, Watanabe Koichiro, Takeuchi Hiroyoshi, Nakajima Shinichiro, Kimura Yoshie, Tsutsumi Yuichiro, Ishii Koichi, Imasaka Yasushi, Kapur Shitij

Schizophrenia Research (Schizophrenia Research) 130 ( 1-3 ) 40 - 46 2011.08

ISSN 0920-9964

Objective: Most patients with schizophrenia first start with a single antipsychotic, and yet most finally end up 'switching' or using 'polypharmacy'. The objective of this study was to examine the evolution of antipsychotic switch and polypharmacy in the real-world from a longitudinal perspective. Methods: A systematic review of longitudinal antipsychotic prescriptions in 300 patients with schizophrenia (ICD-10) for up to 2. years after their first visit to one of the 4 participating psychiatric clinics in Tokyo, Japan between January, 2007 and June, 2008, was conducted. Reasons for prescription change were also examined. The evolution of switching and polypharmacy was studied, and prescribed doses were compared to suggested dose ranges by the Texas Medication Algorithm Project (TMAP). Results: 208 patients started their antipsychotic treatment with monotherapy. 34.1% of the patients gave up monotherapy with an initial antipsychotic to move to antipsychotic switch (27.4%) and/or polypharmacy (17.8%) within 2. years. The main reason for antipsychotic switch was 'ineffectiveness'; interestingly, this happened despite the fact that the monotherapy dose was below the recommended range in 47.4% of the antipsychotic switch. In a subgroup of 100 patients who started as antipsychotic-free, 2-year prevalence rates of switching and antipsychotic polypharmacy were 27.0% and 18.0%, respectively, and polypharmacy was resorted to after a median of 1 antipsychotic had been tried for 84. days (median). Conclusions: These findings raise a concern that physicians may perform an antipsychotic switch without exploring the entire dose range and resort to antipsychotic polypharmacy without trying an adequate number of antipsychotics.

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Dopamine D₂ receptor occupancy and clinical effects

Uchida Hiroyuki, Takeuchi Hiroyoshi, Graff-Guerrero Ariel, Suzuki Takefumi, Watanabe Koichiro, Mamo David C.

Journal of Clinical Psychopharmacology 31 ( 4 ) 497 - 502 2011.08

ISSN 0271-0749

Positron emission tomography (PET) studies proposed a therapeutic window of D₂ receptor occupancy (65%-80%) of antipsychotics for the treatment of schizophrenia in young adults. However, this conclusion has been drawn from clinical PET studies using small sample sizes (<20). Prospective PET studies that measured D₂ occupancy levels and assessed extrapyramidal side effects (EPS) and/or treatment response induced by antipsychotics (excluding partial agonists) were identified, using MEDLINE and EMBASE (last search: March 2010). Individual subjects were divided into 2 groups based on EPS status (ie, presence or lack of newly emergent EPS) and treatment response (ie, a â‰¥ 25% or â‰¥ 50% reduction in the Positive and Negative Syndrome Scale or Brief Psychiatric Rating Scale). To evaluate the performance of this binary classification, sensitivity, specificity, and accuracy of consecutive cutoff points in the D₂ occupancy were calculated: Accuracy = (True Positive + True Negative)/Total N. Twelve studies, including a total of 82 subjects, were included in our analyses. The cutoff points associated with 0.5 or greater in both sensitivity and specificity with the greatest accuracy were 77% to 78% for EPS, 60% for a 25% or greater symptom reduction, and 72% for a 50% or greater symptom reduction. These findings support the presence of a therapeutic window of 60% to 78% D₂ occupancy of antipsychotics in young adults with schizophrenia and may suggest the presence of a continuum of effectiveness with increasing occupancy within this therapeutic window.

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How long to wait before reducing antipsychotic dosage in stabilized patients with schizophrenia? A retrospective chart review

Takeuchi Hiroyoshi, Suzuki Takefumi, Uchida Hiroyuki, Kikuchi Toshiaki, Nakajima Shinichiro, Manki Hiroshi, Watanabe Koichiro, Kashima Haruo

Journal of Psychiatric Research (Journal of Psychiatric Research) 45 ( 8 ) 1083 - 1088 2011.08

ISSN 0022-3956

Objective: Antipsychotic dose reduction is generally recommended to occur after six months of clinical stabilization despite inadequate evidence. This timing issue was addressed in this study. Methods: This is an observational, retrospective and medical chart-based study. Inclusion criteria were (1) diagnosis of schizophrenia (DSM-IV), (2) being acutely psychotic at their first outpatient visit from May, 2002 to April, 2003, (3) having responded to antipsychotics and achieved clinical stabilization of acute symptoms, indexed as a fixation of regimen for four or more weeks, and (4) having one or more years of follow-up. Patients who had their antipsychotic doses reduced were then identified, and they were divided into two groups based on the waiting period before dose reduction: <24 weeks (Early Group) and ≥24 weeks (Standard Group). The rate of dose escalation for ≥20% during follow-up period was investigated as a proxy of clinical worsening. Results: After excluding stable patients at baseline, 211 patients met inclusion criteria. The mean ± SD waiting period before reducing antipsychotics was 122 ± 102 days. The rates of patients needing dose escalation were not significantly different between patients whose dose was reduced (N = 83) and those who was not (N = 128) (57.8% vs. 59.4%), and between Early Group (N = 59) and Standard Group (N = 24) (61.0% vs. 50.0%) although the reduction rate in antipsychotic dosage was significantly greater in Early Group (58.7% vs. 43.3%, p < 0.05). Conclusion: These findings may indicate that timeline until antipsychotic reduction in stable patients with schizophrenia could be earlier than recommended, although caution is needed in interpreting our retrospective results.

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Plasma substance P level in patients with schizophrenia

Ishida Takuto, Uchida Hiroyuki, Suzuki Takefumi, Nakajima Shinichiro, Watanabe Koichiro, Kashima Haruo

Psychiatry and Clinical Neurosciences 65 ( 5 ) 526 - 528 2011.08

ISSN 1323-1316

Aspiration pneumonia is a serious health concern in older patients with schizophrenia. In this study, we examined clinical and demographic variables that could impact the plasma substance P level, which is a useful predictive biomarker of aspiration. Thirty-four patients were included (mean age ± SD: 70.9 ± 10.8 years). A greater number of cigarettes/day and a higher antipsychotic dosage were found to be associated with a lower plasma substance P level, while age showed a trend-level effect. This finding suggests the need for intensive observation for prevention of aspiration pneumonia in heavy smokers who are receiving a higher antipsychotic dose in this senior population.

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Dopamine D<inf>2</inf> receptor occupancy and clinical effects: A systematic review and pooled analysis

Uchida H., Takeuchi H., Graff-Guerrero A., Suzuki T., Watanabe K., Mamo D.

Journal of Clinical Psychopharmacology (Journal of Clinical Psychopharmacology) 31 ( 4 ) 497 - 502 2011.08

ISSN 02710749

Positron emission tomography (PET) studies proposed a therapeutic window of D2 receptor occupancy (65%-80%) of antipsychotics for the treatment of schizophrenia in young adults. However, this conclusion has been drawn from clinical PET studies using small sample sizes (<20). Prospective PET studies that measured D2 occupancy levels and assessed extrapyramidal side effects (EPS) and/or treatment response induced by antipsychotics (excluding partial agonists) were identified, using MEDLINE and EMBASE (last search: March 2010). Individual subjects were divided into 2 groups based on EPS status (ie, presence or lack of newly emergent EPS) and treatment response (ie, a â‰¥ 25% or â‰¥ 50% reduction in the Positive and Negative Syndrome Scale or Brief Psychiatric Rating Scale). To evaluate the performance of this binary classification, sensitivity, specificity, and accuracy of consecutive cutoff points in the D2 occupancy were calculated: Accuracy = (True Positive + True Negative)/Total N. Twelve studies, including a total of 82 subjects, were included in our analyses. The cutoff points associated with 0.5 or greater in both sensitivity and specificity with the greatest accuracy were 77% to 78% for EPS, 60% for a 25% or greater symptom reduction, and 72% for a 50% or greater symptom reduction. These findings support the presence of a therapeutic window of 60% to 78% D2 occupancy of antipsychotics in young adults with schizophrenia and may suggest the presence of a continuum of effectiveness with increasing occupancy within this therapeutic window. © 2011 Lippincott Williams & Wilkins.

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Plasma substance P level in patients with schizophrenia: A cross-sectional study

Ishida T., Uchida H., Suzuki T., Nakajima S., Watanabe K., Kashima H.

Psychiatry and Clinical Neurosciences (Psychiatry and Clinical Neurosciences) 65 ( 5 ) 526 - 528 2011.08

ISSN 13231316

Aspiration pneumonia is a serious health concern in older patients with schizophrenia. In this study, we examined clinical and demographic variables that could impact the plasma substance P level, which is a useful predictive biomarker of aspiration. Thirty-four patients were included (mean age ± SD: 70.9 ± 10.8 years). A greater number of cigarettes/day and a higher antipsychotic dosage were found to be associated with a lower plasma substance P level, while age showed a trend-level effect. This finding suggests the need for intensive observation for prevention of aspiration pneumonia in heavy smokers who are receiving a higher antipsychotic dose in this senior population. © 2011 Japanese Society of Psychiatry and Neurology.

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Low dose vs standard dose of antipsychotics for relapse prevention in schizophrenia

Uchida Hiroyuki, Suzuki Takefumi, Takeuchi Hiroyoshi, Arenovich Tamara, Mamo David C.

Schizophrenia Bulletin 37 ( 4 ) 788 - 799 2011.07

ISSN 0586-7614

Background: It remains unknown as to whether the antipsychotic dose needed for the acute-phase treatment of schizophrenia is also necessary for relapse prevention. Aim: To compare the efficacy between standard dose [(World Health Organization daily defined dose (DDD)] vs low dose (≥50% to <1 DDD) or very low dose (<50% DDD) for relapse prevention in schizophrenia. Data source: Double-blind, randomized, controlled trials with a follow-up duration of ≥24 weeks, including ≥2 dosage groups of the same antipsychotic drug for relapse prevention in schizophrenia, were searched using MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE (last search: August 2009). Data extraction: Data on overall treatment failure, hospitalization, relapse, and dropouts due to side effects were extracted and combined in a meta-analysis. Data synthesis: Thirteen studies with 1395 subjects were included in this meta-analysis. Compared with the standard-dose treatment, the low-dose therapy did not show any statistically significant difference in overall treatment failure or hospitalization, while the standard dose showed a trend-level (P =. 05) superiority in risk of relapse. The very low-dose group was inferior to the standard-dose group in all efficacy parameters. No significant difference was found in the rate of dropouts due to side effects between either standard dose vs low dose or very low dose. Conclusions: Although antipsychotic treatment with ≥50% to <1 DDD may be as effective as standard-dose therapy, there are insufficient clinical trial data to draw firm conclusions on standard- vs low-dose maintenance antipsychotic therapy for schizophrenia.

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Gender differences in age, period, and birth-cohort effects on the suicide mortality rate in Japan, 1985-2006.

Odagiri Y, Uchida H, Nakano M

Asia-Pacific journal of public health 23 ( 4 ) 581 - 7 2011.07

ISSN 1010-5395

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Low dose vs standard dose of antipsychotics for relapse prevention in schizophrenia: Meta-analysis

Uchida H., Suzuki T., Takeuchi H., Arenovich T., Mamo D.C.

Schizophrenia Bulletin (Schizophrenia Bulletin) 37 ( 4 ) 788 - 799 2011.07

ISSN 05867614

Background: It remains unknown as to whether the antipsychotic dose needed for the acute-phase treatment of schizophrenia is also necessary for relapse prevention. Aim: To compare the efficacy between standard dose [(World Health Organization daily defined dose (DDD)] vs low dose (≥50% to <1 DDD) or very low dose (<50% DDD) for relapse prevention in schizophrenia. Data source: Double-blind, randomized, controlled trials with a follow-up duration of ≥24 weeks, including ≥2 dosage groups of the same antipsychotic drug for relapse prevention in schizophrenia, were searched using MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE (last search: August 2009). Data extraction: Data on overall treatment failure, hospitalization, relapse, and dropouts due to side effects were extracted and combined in a meta-analysis. Data synthesis: Thirteen studies with 1395 subjects were included in this meta-analysis. Compared with the standard-dose treatment, the low-dose therapy did not show any statistically significant difference in overall treatment failure or hospitalization, while the standard dose showed a trend-level (P =. 05) superiority in risk of relapse. The very low-dose group was inferior to the standard-dose group in all efficacy parameters. No significant difference was found in the rate of dropouts due to side effects between either standard dose vs low dose or very low dose. Conclusions: Although antipsychotic treatment with ≥50% to <1 DDD may be as effective as standard-dose therapy, there are insufficient clinical trial data to draw firm conclusions on standard- vs low-dose maintenance antipsychotic therapy for schizophrenia. © The Author 2011. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.

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Sulfonated poly(arylene ether sulfone ketone) multiblock copolymers with highly sulfonated blocks. Long-term fuel cell operation and post-test analyses.

Bae B, Miyatake K, Uchida M, Uchida H, Sakiyama Y, Okanishi T, Watanabe M

ACS applied materials & interfaces 3 ( 7 ) 2786 - 93 2011.07

ISSN 1944-8244

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Predicting dopamine D₂ receptor occupancy from plasma levels of antipsychotic drugs

Uchida Hiroyuki, Takeuchi Hiroyoshi, Graff-Guerrero Ariel, Suzuki Takefumi, Watanabe Koichiro, Mamo David C.

Journal of Clinical Psychopharmacology 31 ( 3 ) 318 - 325 2011.06

ISSN 0271-0749

Measuring dopamine D2 receptor occupancy levels using positron emission tomography (PET) is still widely unavailable. The objective of this study was to evaluate the accuracy of predicting D2 occupancy from the antipsychotic plasma level in patients with schizophrenia. Positron emission tomographic studies that measured plasma levels of antipsychotics and their corresponding D2 occupancy levels were identified, using MEDLINE and EMBASE (last search: March 2010). Antipsychotics that were investigated in a total of 20 subjects or more were included. All data points for each antipsychotic were fit to a one-site binding model to estimate the total plasma concentration of each antipsychotic associated with a 50% occupancy (ED50) of brain D2 receptors. The mean prediction error and the root mean squared prediction error were used to measure the predictive performance of individual D2 receptor occupancies from plasma drug levels derived from a one-site occupancy model using an ED50 value calculated for each data point. A total of 34 treatment arms from 23 studies involving 281 subjects were included. The mean (95% confidence interval) prediction errors and root squared prediction errors were as low as 0.0 (-1.8 to 1.8) and 8.9 (7.6-10.2) for risperidone (n = 98); 0.0 (-3.5 to 3.5) and 15.1 (12.9-17.3) for clozapine (n = 75); -0.1 (-1.2 to 1.2), 0.0 (-1.9 to 1.9), and 4.6 (3.5-5.8) for olanzapine (n = 42); 0.1 (-3.4 to 3.5) and 9.9 (7.3-12.5) for haloperidol (n = 35); and -0.1 (-3.3 to 3.1) and 12.3 (8.8-15.7) for ziprasidone (n = 31), respectively. These findings suggest that D2 occupancy of antipsychotics could be estimated with a high degree of accuracy using widely available plasma levels.

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A tipping point in drug dosing in late-life schizophrenia

Tsuboi Takashi, Suzuki Takefumi, Uchida Hiroyuki

Current Psychiatry Reports (Current Psychiatry Reports) 13 ( 3 ) 225 - 233 2011.06

ISSN 1523-3812

Minimally effective doses of antipsychotics are likely influenced by several clinical and demographic characteristics of patients, with age being one of the most important elements. In light of age-related physiologic changes as well as interindividual differences in pharmacokinetic and pharmacodynamic systems, individualized dosing with regard to age will be critically important for safer drug treatment for older patients with schizophrenia. In the present review, we propose the following cautious psychopharmacologic interventions for this population: 1) simple regimen (avoid polypharmacy), 2) be aware of the presence of patients who are very sensitive to drugs, 3) gradual dose titration, and 4) timely and thorough assessments of therapeutic and side effects. The age-related antipsychotic sensitivity highlights the importance of finding the lowest possible effective dose of antipsychotic drugs as patients with schizophrenia age to maximize therapeutic effects and minimize side effects.

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Adsorption and oxidation of carbon monoxide on Pt/C, Pt3Co/C, and PtRu/C catalysts studied by in-situ attenuated total reflection Fourier-transform infrared.

Sato T, Kunimatsu K, Watanabe M, Uchida H

Journal of nanoscience and nanotechnology 11 ( 6 ) 5123 - 30 2011.06

ISSN 1533-4880

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Characterization of systemic and histologic injury after crush syndrome and intervals of reperfusion in a small animal model.

Murata I, Ooi K, Sasaki H, Kimura S, Ohtake K, Ueda H, Uchida H, Yasui N, Tsutsui Y, Yoshizawa N, Hirotsu I, Morimoto Y, Kobayashi J

The Journal of trauma 70 ( 6 ) 1453 - 63 2011.06

ISSN 0022-5282

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Predicting dopamine D<inf>2</inf> receptor occupancy from plasma levels of antipsychotic drugs: A systematic review and pooled analysis

Uchida H., Takeuchi H., Graff-Guerrero A., Suzuki T., Watanabe K., Mamo D.

Journal of Clinical Psychopharmacology (Journal of Clinical Psychopharmacology) 31 ( 3 ) 318 - 325 2011.06

ISSN 02710749

Measuring dopamine D2 receptor occupancy levels using positron emission tomography (PET) is still widely unavailable. The objective of this study was to evaluate the accuracy of predicting D2 occupancy from the antipsychotic plasma level in patients with schizophrenia. Positron emission tomographic studies that measured plasma levels of antipsychotics and their corresponding D2 occupancy levels were identified, using MEDLINE and EMBASE (last search: March 2010). Antipsychotics that were investigated in a total of 20 subjects or more were included. All data points for each antipsychotic were fit to a one-site binding model to estimate the total plasma concentration of each antipsychotic associated with a 50% occupancy (ED50) of brain D2 receptors. The mean prediction error and the root mean squared prediction error were used to measure the predictive performance of individual D2 receptor occupancies from plasma drug levels derived from a one-site occupancy model using an ED50 value calculated for each data point. A total of 34 treatment arms from 23 studies involving 281 subjects were included. The mean (95% confidence interval) prediction errors and root squared prediction errors were as low as 0.0 (-1.8 to 1.8) and 8.9 (7.6-10.2) for risperidone (n = 98); 0.0 (-3.5 to 3.5) and 15.1 (12.9-17.3) for clozapine (n = 75); -0.1 (-1.2 to 1.2), 0.0 (-1.9 to 1.9), and 4.6 (3.5-5.8) for olanzapine (n = 42); 0.1 (-3.4 to 3.5) and 9.9 (7.3-12.5) for haloperidol (n = 35); and -0.1 (-3.3 to 3.1) and 12.3 (8.8-15.7) for ziprasidone (n = 31), respectively. These findings suggest that D2 occupancy of antipsychotics could be estimated with a high degree of accuracy using widely available plasma levels. © 2011 Lippincott Williams & Wilkins.

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広汎性発達障害児の人物画研究　DAM項目による身体部位表現の分析

明翫光宜, 望月知世, 内田裕之, 辻井正次

小児の精神と神経 ((一社)日本小児精神神経学会) 51 ( 2 ) 157 - 168 2011.06

ISSN 0559-9040

本研究では、広汎性発達障害児の人物画の特徴を捉えるために、定型発達児との比較研究を行った。対象は広汎性発達障害群30名(男児)、定型発達群97名(男児)であった。DAM項目について両群を比較したところ、DAM-IQなどの総合指標だけの分析では広汎性発達障害の心理査定に限界があり、人物画に描かれている身体部位表現に注目することの重要性を示唆した。(著者抄録)

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