研究者詳細 - 内田　裕之

論文 - 内田　裕之

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Therapeutic Window for Striatal Dopamine D2/3 Receptor Occupancy in Older Patients With Schizophrenia: A Pilot PET Study.

Uchida H, Suzuki T, Graff-Guerrero A, Mulsant BH, Pollock BG, Arenovich T, Rajji TK, Mamo DC

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry 2012年10月

ISSN 1064-7481

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The 3rd Schizophrenia International Research Society Conference, 14-18 April 2012, Florence, Italy

Abbs Brandon, Achalia Rashmin M., Adelufosi Adegoke O., Aktener Ahmet Yiǧit, Beveridge Natalie J., Bhakta Savita G., Blackman Rachael K., Bora Emre, Byun M. S., Cabanis Maurice, Carrion Ricardo, Castellani Christina A., Chow Tze Jen, Dmitrzak-Weglarz M., Gayer-Anderson Charlotte, Gomes Felipe V., Haut Kristen, Hori Hiroaki, Kantrowitz Joshua T., Kishimoto Taishiro, Lee Frankie H F, Lin Ashleigh, Palaniyappan Lena, Quan Meina, Rubio Maria D., de Azúa Sonia Ruiz, Sahoo Saddichha, Strauss Gregory P., Szczepankiewicz Aleksandra, Thompson Andrew D., Trotta Antonella, Tully Laura M., Uchida Hiroyuki, Velthorst Eva, Young Jared W., O'Shea Anne, DeLisi Lynn E.

Schizophrenia Research 141 （ 1 ） 2012年10月

ISSN 0920-9964

The 3rd Schizophrenia International Research Society Conference was held in Florence, Italy, April 14-18, 2012 and this year had as its emphasis, "The Globalization of Research". Student travel awardees served as rapporteurs for each oral session and focused their summaries on the most significant findings that emerged and the discussions that followed. The following report is a composite of these summaries. We hope that it will provide an overview for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research.

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The 3rd Schizophrenia International Research Society Conference, 14-18 April 2012, Florence, Italy: Summaries of oral sessions

Abbs B., Achalia R.M., Adelufosi A.O., Aktener A.Y., Beveridge N.J., Bhakta S.G., Blackman R.K., Bora E., Byun M.S., Cabanis M., Carrion R., Castellani C.A., Chow T.J., Dmitrzak-Weglarz M., Gayer-Anderson C., Gomes F.V., Haut K., Hori H., Kantrowitz J.T., Kishimoto T., Lee F.H.F., Lin A., Palaniyappan L., Quan M., Rubio M.D., de Azúa S.R., Sahoo S., Strauss G.P., Szczepankiewicz A., Thompson A.D., Trotta A., Tully L.M., Uchida H., Velthorst E., Young J.W., O'Shea A., DeLisi L.E.

Schizophrenia Research （Schizophrenia Research） 141 （ 1 ） e1 - e24 2012年10月

ISSN 09209964

The 3rd Schizophrenia International Research Society Conference was held in Florence, Italy, April 14-18, 2012 and this year had as its emphasis, "The Globalization of Research". Student travel awardees served as rapporteurs for each oral session and focused their summaries on the most significant findings that emerged and the discussions that followed. The following report is a composite of these summaries. We hope that it will provide an overview for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research. © 2012 Elsevier B.V.

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研究と報告　日本版Vineland-II適応行動尺度の開発　不適応行動尺度の信頼性・妥当性に関する報告

伊藤大幸, 谷伊織, 行廣隆次, 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） 54 （ 9 ） 889 - 898 2012年09月

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,不適応行動尺度の信頼性・妥当性を検証した。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。内的整合性を示すα係数は,2つの下位尺度および全体尺度とも良好な値を示した。一般群と自閉症スペクトラム群の尺度得点を比較したところ,顕著な得点差がみられ,幼児期から青年・成人期にかけて,得点差が拡大する傾向がみられた。知能指数との相関は中程度までにとどまり,知的能力とは独立の構成概念を測定していることが示された。これらの結果は不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)

Human neuroglobin functions as an oxidative stress-responsive sensor for neuroprotection.

Watanabe S, Takahashi N, Uchida H, Wakasugi K

The Journal of biological chemistry 287 （ 36 ） 30128 - 38 2012年08月

ISSN 0021-9258

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Dental conditions in inpatients with schizophrenia

Tani Hideaki, Uchida Hiroyuki, Suzuki Takefumi, Shibuya Yumi, Shimanuki Hiroshi, Watanabe Koichiro, Den Ryosuke, Nishimoto Masahiko, Hirano Jinichi, Takeuchi Hiroyoshi, Nio Shintaro, Nakajima Shinichiro, Kitahata Ryosuke, Tsuboi Takashi, Tsunoda Kenichi, Kikuchi Toshiaki, Mimura Masaru

BMC Oral Health 12 （ 1 ） 2012年08月

Background: Clinical relevance of dental caries is often underestimated in patients with schizophrenia. The objective of this study was to examine dental caries and to identify clinical and demographic variables associated with poor dental condition in patients with schizophrenia.Methods: Inpatients with schizophrenia received a visual oral examination of their dental caries, using the decayed-missing-filled teeth (DMFT) index. This study was conducted in multiple sites in Japan, between October and December, 2010. A univariate general linear model was used to examine the effects of the following variables on the DMFT score: age, sex, smoking status, daily intake of sweets, dry mouth, frequency of daily tooth brushing, tremor, the Clinical Global Impression-Schizophrenia Overall severity score, and the Cumulative Illness Rating Scale for Geriatrics score.Results: 523 patients were included in this study (mean ± SD age = 55.6 ± 13.4 years; 297 men). A univariate general linear model showed significant effects of age group, smoking, frequency of daily tooth brushing, and tremor (all p's < 0.001) on the DMFT score (Corrected Model: F _{(23, 483)} = 3.55, p < 0.001, R ² = 0.42) . In other words, older age, smoking, tremor burden, and less frequent tooth brushing were associated with a greater DMFT score.Conclusions: Given that poor dental condition has been related with an increased risk of physical co-morbidities, physicians should be aware of patients' dental status, especially for aged smoking patients with schizophrenia. Furthermore, for schizophrenia patients who do not regularly brush their teeth or who exhibit tremor, it may be advisable for caregivers to encourage and help them to perform tooth brushing more frequently.

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Dental conditions in inpatients with schizophrenia: A large-scale multi-site survey

Tani H., Uchida H., Suzuki T., Shibuya Y., Shimanuki H., Watanabe K., Den R., Nishimoto M., Hirano J., Takeuchi H., Nio S., Nakajima S., Kitahata R., Tsuboi T., Tsunoda K., Kikuchi T., Mimura M.

BMC Oral Health （BMC Oral Health） 12 （ 1 ） 32 2012年08月

Background: Clinical relevance of dental caries is often underestimated in patients with schizophrenia. The objective of this study was to examine dental caries and to identify clinical and demographic variables associated with poor dental condition in patients with schizophrenia.Methods: Inpatients with schizophrenia received a visual oral examination of their dental caries, using the decayed-missing-filled teeth (DMFT) index. This study was conducted in multiple sites in Japan, between October and December, 2010. A univariate general linear model was used to examine the effects of the following variables on the DMFT score: age, sex, smoking status, daily intake of sweets, dry mouth, frequency of daily tooth brushing, tremor, the Clinical Global Impression-Schizophrenia Overall severity score, and the Cumulative Illness Rating Scale for Geriatrics score.Results: 523 patients were included in this study (mean ± SD age = 55.6 ± 13.4 years; 297 men). A univariate general linear model showed significant effects of age group, smoking, frequency of daily tooth brushing, and tremor (all p's < 0.001) on the DMFT score (Corrected Model: F (23, 483) = 3.55, p < 0.001, R 2 = 0.42) . In other words, older age, smoking, tremor burden, and less frequent tooth brushing were associated with a greater DMFT score.Conclusions: Given that poor dental condition has been related with an increased risk of physical co-morbidities, physicians should be aware of patients' dental status, especially for aged smoking patients with schizophrenia. Furthermore, for schizophrenia patients who do not regularly brush their teeth or who exhibit tremor, it may be advisable for caregivers to encourage and help them to perform tooth brushing more frequently. © 2012 Tani et al.; licensee BioMed Central Ltd.

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A cross-sectional study of plasma risperidone levels with risperidone long-acting injectable

Ikai Saeko, Remington Gary, Suzuki Takefumi, Takeuchi Hiroyoshi, Tsuboi Takashi, Den Ryosuke, Hirano Jinichi, Tsunoda Kenichi, Nishimoto Masahiko, Watanabe Koichiro, Mimura Masaru, Mamo David, Uchida Hiroyuki

Journal of Clinical Psychiatry 73 （ 8 ） 1147 - 1152 2012年08月

ISSN 0160-6689

Objective: While 65%-80% occupancy of dopamine D ₂ receptors with antipsychotics has been proposed to achieve optimal therapeutic response during acute treatment of schizophrenia, it remains unclear as to whether it is also necessary to maintain D ₂ receptor occupancy within this "safe" window for ongoing maintenance treatment. The data are especially scarce for long-acting antipsychotic formulations. Method: Clinically stable patients with schizophrenia (DSM-IV) receiving a stable dose of risperidone long-acting injectable (LAI) as antipsychotic monotherapy for at least 3 months and free of any psychiatric hospitalization over the past 6 months were included. Dopamine D ₂ receptor occupancy levels at trough were estimated from plasma concentrations of risperidone plus 9-hydroxyrisperidone immediately before the intramuscular injection of risperidone LAI, using a 1-site binding model derived from our previous positron emission tomography data. This study was conducted from October to December 2011. Results: 36 patients were included in this study (mean ± SD age, 49.3 ± 14.0 years; mean ± SD dose and interval of injections, 38.2 ± 11.6 mg and 16.5 ± 14.0 days, respectively). Mean ± SD D ₂ receptor occupancy was 62.1% ± 15.4%; 52.8% of the subjects (n = 19) did not demonstrate an occupancy of ≥ 65%. On the other hand, 13.9% (n = 5) showed a D ₂ occupancy as high as over 80% at the estimated trough. Conclusions: More than half of patients taking risperidone LAI maintained clinical stability without achieving continuous blockade of dopamine D ₂ receptors ≥ 65% in real-world clinical settings. Results suggest that sustained dopamine D ₂ receptor occupancy levels of ? 65% may not be necessary for maintenance treatment with risperidone LAI in schizophrenia.

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A cross-sectional study of plasma risperidone levels with risperidone long-acting injectable: Implications for dopamine D<inf>2</inf> receptor occupancy during maintenance treatment in schizophrenia

Ikai S., Remington G., Suzuki T., Takeuchi H., Tsuboi T., Den R., Hirano J., Tsunoda K., Nishimoto M., Watanabe K., Mimura M., Mamo D., Uchida H.

Journal of Clinical Psychiatry （Journal of Clinical Psychiatry） 73 （ 8 ） 1147 - 1152 2012年08月

ISSN 01606689

Objective: While 65%-80% occupancy of dopamine D2 receptors with antipsychotics has been proposed to achieve optimal therapeutic response during acute treatment of schizophrenia, it remains unclear as to whether it is also necessary to maintain D2 receptor occupancy within this "safe" window for ongoing maintenance treatment. The data are especially scarce for long-acting antipsychotic formulations. Method: Clinically stable patients with schizophrenia (DSM-IV) receiving a stable dose of risperidone long-acting injectable (LAI) as antipsychotic monotherapy for at least 3 months and free of any psychiatric hospitalization over the past 6 months were included. Dopamine D2 receptor occupancy levels at trough were estimated from plasma concentrations of risperidone plus 9-hydroxyrisperidone immediately before the intramuscular injection of risperidone LAI, using a 1-site binding model derived from our previous positron emission tomography data. This study was conducted from October to December 2011. Results: 36 patients were included in this study (mean ± SD age, 49.3 ± 14.0 years; mean ± SD dose and interval of injections, 38.2 ± 11.6 mg and 16.5 ± 14.0 days, respectively). Mean ± SD D2 receptor occupancy was 62.1% ± 15.4%; 52.8% of the subjects (n = 19) did not demonstrate an occupancy of ≥ 65%. On the other hand, 13.9% (n = 5) showed a D2 occupancy as high as over 80% at the estimated trough. Conclusions: More than half of patients taking risperidone LAI maintained clinical stability without achieving continuous blockade of dopamine D2 receptors ≥ 65% in real-world clinical settings. Results suggest that sustained dopamine D2 receptor occupancy levels of ? 65% may not be necessary for maintenance treatment with risperidone LAI in schizophrenia. © Copyright 2012 Physicians Postgraduate Press, Inc.

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Tips on how to publish your data in English

Uchida H.

Japanese Journal of Neuropsychopharmacology （Japanese Journal of Neuropsychopharmacology） 32 （ 3 ） 155 - 159 2012年06月

ISSN 1340-2544

Japanese researchers often find it difficult to write up academic reports in English, which may be associated with a perceived "language barrier." However, in fact, it is "emotional barrier" that discourages "potential" researchers from publishing their data. The plain English that we have learnt at school is sufficient to write academic articles in English. What is important is your guts, determination, and perseverance. In this article, tips on how to practically publish your data in English are presented.

[Tips on how to publish your data in English].

Uchida H

Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology 32 （ 3 ） 155 - 9 2012年06月

ISSN 1340-2544

Nitrite reduces ischemia/reperfusion-induced muscle damage and improves survival rates in rat crush injury model.

Murata I, Nozaki R, Ooi K, Ohtake K, Kimura S, Ueda H, Nakano G, Sonoda K, Inoue Y, Uchida H, Kanamoto I, Morimoto Y, Kobayashi J

The journal of trauma and acute care surgery 72 （ 6 ） 1548 - 54 2012年06月

ISSN 2163-0755

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抗精神病薬用量変更後の血中濃度を予測する試み

内田裕之, Mamo David C., Pollock Bruce G., 鈴木健文, 角田健一, 渡邊衡一郎, Bies Robert R.

臨床薬理の進歩（(公財)臨床薬理研究振興財団）（ 33 ） 115 - 121 2012年06月

ISSN 0914-4366

薬物血中動態を予測する方法の一つにPopulation Pharmacokinetics(PPK)法がある。今回、リスペリドン用量変更後の血中濃度をPPK法で予測する手法の信頼性と妥当性について検討した。検討方法は、リスペリドン投与中の統合失調症患者で臨床上用量変更が必要な50例を対象に、薬物血漿中濃度を任意の2時点で測定し、それをもとに経口用量変更後の血漿中濃度を予測するPPKモデルの精度を検証した。その結果、PPK法を用いることで、用量変更を行う前に変更後の血漿中濃度を高い精度で予測できることが確認された。

Defining treatment-resistant schizophrenia and response to antipsychotics

Suzuki Takefumi, Remington Gary, Mulsant Benoit H., Uchida Hiroyuki, Rajji Tarek K., Graff-Guerrero Ariel, Mimura Masaru, Mamo David C.

Psychiatry Research 197 （ 1-2 ） 1 - 6 2012年05月

ISSN 0165-1781

Treatment-resistant schizophrenia (TRS) has been defined mainly by severity of (positive) symptoms and response to antipsychotics derived from a relative change in the representative scales (most frequently ≥. 20% decrease in the Positive and Negative Syndrome Scale: PANSS), but these definitions have not necessarily been consistent. Integrating past evidence and real-world practicability, we propose that TRS be defined by at least two failed adequate trials with different antipsychotics (at chlorpromazine-equivalent doses of ≥. 600. mg/day for ≥. 6 consecutive weeks) that could be retrospective or preferably include prospective failure to respond to one or more antipsychotic trials. In addition, our proposed criteria require both a score of ≥. 4 on the Clinical Global Impression (CGI)-Severity and a score of ≤. 49 on the Functional Assessment for Comprehensive Treatment of Schizophrenia (FACT-Sz) or ≤. 50 on the Global Assessment of Functioning (GAF) scales to define TRS. Once TRS is established, we propose that subsequent treatment response be defined based on a CGI-Change score of ≤. 2, a ≥. 20% decrease on the total PANSS or Brief Psychiatric Rating Scale (BPRS) scores, and an increase of ≥. 20 points on the FACT-Sz or GAF. While these suggestions provide a pragmatic framework for TRS classification, they need to be tested in future trials.

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Defining treatment-resistant schizophrenia and response to antipsychotics: A review and recommendation

Suzuki T., Remington G., Mulsant B., Uchida H., Rajji T., Graff-Guerrero A., Mimura M., Mamo D.

Psychiatry Research （Psychiatry Research） 197 （ 1-2 ） 1 - 6 2012年05月

ISSN 01651781

Treatment-resistant schizophrenia (TRS) has been defined mainly by severity of (positive) symptoms and response to antipsychotics derived from a relative change in the representative scales (most frequently ≥. 20% decrease in the Positive and Negative Syndrome Scale: PANSS), but these definitions have not necessarily been consistent. Integrating past evidence and real-world practicability, we propose that TRS be defined by at least two failed adequate trials with different antipsychotics (at chlorpromazine-equivalent doses of ≥. 600. mg/day for ≥. 6 consecutive weeks) that could be retrospective or preferably include prospective failure to respond to one or more antipsychotic trials. In addition, our proposed criteria require both a score of ≥. 4 on the Clinical Global Impression (CGI)-Severity and a score of ≤. 49 on the Functional Assessment for Comprehensive Treatment of Schizophrenia (FACT-Sz) or ≤. 50 on the Global Assessment of Functioning (GAF) scales to define TRS. Once TRS is established, we propose that subsequent treatment response be defined based on a CGI-Change score of ≤. 2, a ≥. 20% decrease on the total PANSS or Brief Psychiatric Rating Scale (BPRS) scores, and an increase of ≥. 20 points on the FACT-Sz or GAF. While these suggestions provide a pragmatic framework for TRS classification, they need to be tested in future trials. © 2012 Elsevier Ltd.

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Dopamine D2 receptor occupancy with risperidone or olanzapine during maintenance treatment of schizophrenia

Mizuno Yuya, Bies Robert R., Remington Gary, Mamo David C., Suzuki Takefumi, Pollock Bruce G., Tsuboi Takashi, Watanabe Koichiro, Mimura Masaru, Uchida Hiroyuki

Progress in Neuro-Psychopharmacology and Biological Psychiatry 37 （ 1 ） 182 - 187 2012年04月

ISSN 0278-5846

In treating schizophrenia, it has been established that 65-80% occupancy of dopamine D2 receptors optimizes therapeutic efficacy while minimizing risks of extrapyramidal symptoms. However, it is unclear as to whether it is necessary to keep D2 receptor occupancy within this therapeutic window to maintain response. In this study, daily peak and trough D2 receptor occupancy levels were estimated in clinically stable patients with schizophrenia (DSM-IV) who were receiving risperidone or olanzapine. Using two collected plasma samples, plasma antipsychotic concentrations at peak and trough were estimated with population pharmacokinetic techniques. Corresponding dopamine D2 receptor occupancy levels were then estimated, using a recently developed model. 35 subjects with stable schizophrenia completed the study (mean ± SD age, 48.8 ± 13.8. years; male [N = 14]; Asians [N = 23], Caucasians [N = 12]; risperidone [N = 20] at 3.2 ± 2.3. mg/day, and olanzapine [N = 15] at 9.2 ± 4.9. mg/day) between September and December 2010. 48.6% (N = 17) did not achieve a continuous blockade of ≥ 65%. Moreover, 11.4% (N = 4) did not achieve the 65% threshold at estimated peak concentrations. In conclusion, approximately half the subjects with stable schizophrenia did not achieve estimated continuous blockade of D2 receptor occupancy of ≥ 65%. The results suggest that sustained D2 receptor occupancy levels of ≥ 65% may not always be necessary for the maintenance treatment of schizophrenia.

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Dopamine D2 receptor occupancy with risperidone or olanzapine during maintenance treatment of schizophrenia: A cross-sectional study

Mizuno Y., Bies R., Remington G., Mamo D., Suzuki T., Pollock B., Tsuboi T., Watanabe K., Mimura M., Uchida H.

Progress in Neuro-Psychopharmacology and Biological Psychiatry （Progress in Neuro-Psychopharmacology and Biological Psychiatry） 37 （ 1 ） 182 - 187 2012年04月

ISSN 02785846

In treating schizophrenia, it has been established that 65-80% occupancy of dopamine D2 receptors optimizes therapeutic efficacy while minimizing risks of extrapyramidal symptoms. However, it is unclear as to whether it is necessary to keep D2 receptor occupancy within this therapeutic window to maintain response. In this study, daily peak and trough D2 receptor occupancy levels were estimated in clinically stable patients with schizophrenia (DSM-IV) who were receiving risperidone or olanzapine. Using two collected plasma samples, plasma antipsychotic concentrations at peak and trough were estimated with population pharmacokinetic techniques. Corresponding dopamine D2 receptor occupancy levels were then estimated, using a recently developed model. 35 subjects with stable schizophrenia completed the study (mean ± SD age, 48.8 ± 13.8. years; male [N = 14]; Asians [N = 23], Caucasians [N = 12]; risperidone [N = 20] at 3.2 ± 2.3. mg/day, and olanzapine [N = 15] at 9.2 ± 4.9. mg/day) between September and December 2010. 48.6% (N = 17) did not achieve a continuous blockade of ≥ 65%. Moreover, 11.4% (N = 4) did not achieve the 65% threshold at estimated peak concentrations. In conclusion, approximately half the subjects with stable schizophrenia did not achieve estimated continuous blockade of D2 receptor occupancy of ≥ 65%. The results suggest that sustained D2 receptor occupancy levels of ≥ 65% may not always be necessary for the maintenance treatment of schizophrenia. © 2011 Elsevier Inc.

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Effects of zonisamide on tardive dyskinesia

Iwata Yusuke, Irie Sachiko, Uchida Hiroyuki, Suzuki Takefumi, Watanabe Koichiro, Iwashita Satoru, Mimura Masaru

Journal of the Neurological Sciences 315 （ 1-2 ） 137 - 140 2012年04月

ISSN 0022-510X

Once developed, tardive dyskinesia (TD) is a challenging condition to treat. The recent evidence has indicated that zonisamide, an antiepileptic drug indicated for partial-onset seizures, may also have beneficial effects for ameliorating dyskinesia in Parkinson's disease. However, this finding has not systematically been tested in psychiatric patients with TD associated with antipsychotic treatment. The objective of this study was to examine the efficacy, tolerability, and safety of zonisamide against TD in these patients. In this 4-week open-label study, subjects who suffered TD were given 50-100 mg/day of add-on zonisamide. Severity of TD was evaluated at the baseline and endpoint, using the Abnormal Involuntary Movement Scale (AIMS). Eleven subjects (6 females; mean ± SD age, 75.5 ± 4.7 years; schizophrenia [N = 6], bipolar affective disorder [N = 2], schizoaffective disorder [N = 1], mental retardation [N = 1], mental retardation with epilepsy [N = 1]; 6 were antipsychotic free at baseline) participated in this study. The AIMS total score (mean ± SD) was significantly decreased from 24.1 ± 5.5 to 19.5 ± 5.9, with 36.4% of the subjects (N = 4) demonstrating 20% or more decrease in the AIMS total score. Treatment with zonisamide was well-tolerated and no participants dropped out prematurely. In conclusion, zonisamide may be safe and effective for the treatment of TD associated with antipsychotic treatment. These preliminary findings need to be further explored by larger well-designed trials.

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Effects of zonisamide on tardive dyskinesia: A preliminary open-label trial

Iwata Y., Irie S., Uchida H., Suzuki T., Watanabe K., Iwashita S., Mimura M.

Journal of the Neurological Sciences （Journal of the Neurological Sciences） 315 （ 1-2 ） 137 - 140 2012年04月

ISSN 0022510X

Once developed, tardive dyskinesia (TD) is a challenging condition to treat. The recent evidence has indicated that zonisamide, an antiepileptic drug indicated for partial-onset seizures, may also have beneficial effects for ameliorating dyskinesia in Parkinson's disease. However, this finding has not systematically been tested in psychiatric patients with TD associated with antipsychotic treatment. The objective of this study was to examine the efficacy, tolerability, and safety of zonisamide against TD in these patients. In this 4-week open-label study, subjects who suffered TD were given 50-100 mg/day of add-on zonisamide. Severity of TD was evaluated at the baseline and endpoint, using the Abnormal Involuntary Movement Scale (AIMS). Eleven subjects (6 females; mean ± SD age, 75.5 ± 4.7 years; schizophrenia [N = 6], bipolar affective disorder [N = 2], schizoaffective disorder [N = 1], mental retardation [N = 1], mental retardation with epilepsy [N = 1]; 6 were antipsychotic free at baseline) participated in this study. The AIMS total score (mean ± SD) was significantly decreased from 24.1 ± 5.5 to 19.5 ± 5.9, with 36.4% of the subjects (N = 4) demonstrating 20% or more decrease in the AIMS total score. Treatment with zonisamide was well-tolerated and no participants dropped out prematurely. In conclusion, zonisamide may be safe and effective for the treatment of TD associated with antipsychotic treatment. These preliminary findings need to be further explored by larger well-designed trials. © 2012 Elsevier B.V. All rights reserved.

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Predicting plasma concentration of risperidone associated with dosage change

Uchida Hiroyuki, Mamo David C., Pollock Bruce G., Suzuki Takefumi, Tsunoda Kenichi, Watanabe Koichiro, Mimura Masaru, Bies Robert R.

Therapeutic Drug Monitoring 34 （ 2 ） 182 - 187 2012年04月

ISSN 0163-4356

Background: Due to high interindividual variability in peripheral pharmacokinetic parameters, dosing of antipsychotics relies on clinical trial and error. This blind process of upward or downward clinical dose titration carries a risk of relapse and adverse effects in the treatment of schizophrenia. Using population pharmacokinetic methods, the authors therefore sought to predict plasma concentrations of risperidone (RIS) plus 9-hydroxyrisperidone (9-OH-RIS) before a dosage change. Methods: Two plasma samples were collected at 2 separate given time points for the measurement of RIS and 9-OH-RIS concentrations from 50 patients with schizophrenia or schizoaffective disorder maintained on risperidone (mean ± SD age = 56 ± 15 years; 39 men). After an oral risperidone dose adjustment, a third sample was collected. The plasma concentration of the third sample was individually predicted in a blinded fashion with the 2 baseline plasma concentrations before dose adjustment and clinical and demographic information, using the mixed-effects model with NONMEM that was derived from the data of the Clinical Antipsychotic Trials in Intervention Effectiveness study. Results: The mean (95% confidence interval) prediction errors (in ng/mL) were as low as 0.0 (-1.3 to 1.4) for RIS and 1.0 (-1.1 to 3.0) for 9-OH-RIS. The observed and predicted concentrations of RIS and 9-OH-RIS were highly correlated (r = 0.96, P < 0.0001 and r = 0.92, P < 0.0001, respectively). Conclusions: Antipsychotic plasma concentrations can be predicted before risperidone dose adjustment. In light of the known relationship between plasma drug concentration, dopamine D2 receptor occupancy, and clinical effects, our results confirm that individualized dosing with the measurement of antipsychotic plasma concentrations has the potential for bedside clinical application.

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