Details of a Researcher - Uchida, Hiroyuki

Papers - Uchida, Hiroyuki

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Radiologic and histologic features of the T2 hyperintensity rim of meningiomas on magnetic resonance images.

Uchida H, Hirano H, Moinuddin FM, Hanaya R, Sadamura Y, Hosoyama H, Yonezawa H, Tokimura H, Yamahata H, Arita K

The neuroradiology journal 30 ( 1 ) 48 - 56 2017.02

ISSN 1971-4009

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Cognition and Dopamine D₂ Receptor Availability in the Striatum in Older Patients with Schizophrenia

Rajji Tarek K., Mulsant Benoit H., Nakajima Shinichiro, Caravaggio Fernando, Suzuki Takefumi, Uchida Hiroyuki, Gerretsen Philip, Mar Wanna, Pollock Bruce G., Mamo David C., Graff-Guerrero Ariel

American Journal of Geriatric Psychiatry 25 ( 1 ) 1 - 10 2017.01

ISSN 1064-7481

Objectives To assess the impact of reducing the dose of antipsychotics on cognition and dopaminergic D₂ receptor availability in the whole striatum, and identify their relationship in patients with schizophrenia aged 50 years or older. Design Open-label prospective PET [¹¹C]-raclopride study. Setting A tertiary care center outpatient setting. Participants Thirty-seven clinically stable participants with schizophrenia or schizoaffective disorder, aged 50 years or greater, and having been treated with olanzapine or risperidone monotherapy at the same dose for at least 6 months. Intervention Gradual reduction in their olanzapine or risperidone daily dose of up to 40%. Measurements Clinical and cognitive assessments, and [¹¹C]-raclopride PET to determine D₂ receptor availability at baseline and after the dose reduction. Main outcome measures were overall cognition and D₂ receptor availability in whole striatum. Results Reducing the antipsychotic dose resulted in an increase in D₂ receptor availability in the whole striatum and an association between D₂ receptor availability and overall cognition despite lack of change in the latter. There was also an association between change in D₂ receptor availability and change in overall cognition. Conclusions Our findings suggest that optimizing D₂ receptor availability by reducing antipsychotic dose allows this system to contribute more significantly to cognitive function in patients with schizophrenia. This uncovered association could be harnessed by cognitive-enhancing interventions.

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Naming for psychotropic drugs

Uchida Hiroyuki, Fleischhacker Wolfgang, Juckel Georg, Gründer Gerhard, Bauer Michael

Pharmacopsychiatry 50 ( 1 ) 1 - 2 2017.01

ISSN 0176-3679

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Religiosity and psychological resilience in patients with schizophrenia and bipolar disorder

Mizuno Y., Hofer A., Frajo-Apor B., Wartelsteiner F., Kemmler G., Pardeller S., Suzuki T., Mimura M., Fleischhacker W. W., Uchida H.

Acta Psychiatrica Scandinavica 2017.01

ISSN 0001-690X

Objective: The impact of religious/spiritual activities on clinical outcomes in patients with serious mental illnesses remains controversial, which was addressed in this international cross-sectional study. Method: Three-hundred sixty-nine subjects were recruited from Austria (n = 189) and Japan (n = 180), consisting of 112 outpatients with paranoid schizophrenia, 120 with bipolar I disorder (DSM-IV), and 137 healthy controls. Religiosity was assessed in terms of attendance and importance of religious/spiritual activities, while resilience was assessed using the 25-item Resilience Scale. General linear models were used to test whether higher religiosity will be associated with higher resilience, higher social functioning, and lower psychopathology. The association between levels of spiritual well-being and resilience was also examined. Results: Attendance of religious services (F_[4,365] = 0.827, P = 0.509) and importance of religion/spirituality (F_[3,365] = 1.513, P = 0.211) did not show significant associations with resilience. Regarding clinical measures, a modest association between higher importance of religion/spirituality and residual manic symptoms was observed in bipolar patients (F_[3,118] = 3.120, P = 0.029). In contrast to the findings regarding religiosity, spiritual well-being showed a strong positive correlation with resilience (r = 0.584, P < 0.001). Conclusion: The protective effect of religiosity in terms of resilience, social functioning, and psychopathology was not evident in our sample. Spiritual well-being appears more relevant to resilience than religiosity.

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Cognition and Dopamine D<inf>2</inf> Receptor Availability in the Striatum in Older Patients with Schizophrenia

Rajji T., Mulsant B., Nakajima S., Caravaggio F., Suzuki T., Uchida H., Gerretsen P., Mar W., Pollock B., Mamo D., Graff-Guerrero A.

American Journal of Geriatric Psychiatry (American Journal of Geriatric Psychiatry) 25 ( 1 ) 1 - 10 2017.01

ISSN 10647481

© 2017 American Association for Geriatric Psychiatry Objectives To assess the impact of reducing the dose of antipsychotics on cognition and dopaminergic D2 receptor availability in the whole striatum, and identify their relationship in patients with schizophrenia aged 50 years or older. Design Open-label prospective PET [11C]-raclopride study. Setting A tertiary care center outpatient setting. Participants Thirty-seven clinically stable participants with schizophrenia or schizoaffective disorder, aged 50 years or greater, and having been treated with olanzapine or risperidone monotherapy at the same dose for at least 6 months. Intervention Gradual reduction in their olanzapine or risperidone daily dose of up to 40%. Measurements Clinical and cognitive assessments, and [11C]-raclopride PET to determine D2 receptor availability at baseline and after the dose reduction. Main outcome measures were overall cognition and D2 receptor availability in whole striatum. Results Reducing the antipsychotic dose resulted in an increase in D2 receptor availability in the whole striatum and an association between D2 receptor availability and overall cognition despite lack of change in the latter. There was also an association between change in D2 receptor availability and change in overall cognition. Conclusions Our findings suggest that optimizing D2 receptor availability by reducing antipsychotic dose allows this system to contribute more significantly to cognitive function in patients with schizophrenia. This uncovered association could be harnessed by cognitive-enhancing interventions.

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Psychological dependence on antidepressants in patients with panic disorder: A cross-sectional study

Fujii K., Suzuki T., Mimura M., Uchida H.

International Clinical Psychopharmacology (International Clinical Psychopharmacology) 32 ( 1 ) 36 - 40 2017.01

ISSN 02681315

© 2016 Wolters Kluwer Health, Inc. No study has investigated psychological dependence on antidepressants in patients with panic disorder, which was addressed in this study. This study was carried out in four psychiatric clinics in Tokyo, Japan. Individuals were eligible if they were outpatients aged 18 years or older and fulfilled the diagnostic criteria for panic disorder (ICD-10). Assessments included the Japanese Versions of the Severity of Dependence Scale (SDS), the Self-Report Version of Panic Disorder Severity Scale (PDSS-SR), and the Quick Inventory of Depressive Symptomatology-Self Report. Eighty-four individuals were included; of these, 30 patients (35.7%) showed psychological dependence on antidepressants (i.e. a total score of ≥5 in the SDS). A multiple regression analysis showed that PDSS scores and illness duration were correlated positively with SDS total scores. A binary regression model showed that absence of remission (i.e. a total score of ≥5 in the PDSS) and longer duration of illness increased the risk of dependence on antidepressants. Approximately one-third of the patients with panic disorder, receiving antidepressants, fulfilled the criteria for psychological dependence on these drugs. The results underscore the need for close monitoring, especially for those who present severe symptomatology or have a chronic course of the illness.

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Efficacy of bevacizumab therapy for unresectable malignant glioma: A retrospective analysis.

Yonezawa H, Hirano H, Uchida H, Habu M, Hanaya R, Oyoshi T, Sadamura Y, Hanada T, Tokimura H, Moinuddin F, Arita K

Molecular and clinical oncology 6 ( 1 ) 105 - 110 2017.01

ISSN 2049-9450

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注意したいセフトリアキソン使用時の合併症

内田裕之

薬事新報 ((株)薬事新報社) ( 2974 ) 13 - 15 2017.01

ISSN 0289-3290

症例は妊娠28週の36歳女性で、5日前より発熱があり、インフルエンザA型と診断された。葛根湯で治療したが、解熱しなかった。発熱は持続し、四肢優位、顔面、体幹に紫斑が出現した。オセルタミビルが処方して自宅療養を継続したが、状態は悪化した。発熱、意識障害、全身に紫斑、子宮収縮による腹痛、性器出血を認め、救急搬送された。第2病日に分娩した。血液培養からメチシリン感受性黄色ブドウ球菌(MSSA)を検出し、経食道心エコーで僧帽弁に10.2×6.9mmの可動性のある疣贅が指摘され、感染性心内膜炎と診断した。敗血症、DICの状態で、多発脳梗塞、感染性脳動脈瘤、脳出血、及び両側肺、脾臓、眼底など全身性に敗血症性塞栓症を合併した。第2病日からセフトリアキソン(CTRX)を開始した。第51病日に腹痛を訴え、血液検査では肝胆道系酵素の上昇を認めた。CTを再検査し、総胆管結石、胆管拡張を認め、経過からCTRXによる胆泥形成、胆管炎と診断した。抗菌薬治療はセフォタキシムへ変更し、慎重に経過観察した。77病日に軽快退院した。

Patients’ Knowledge about Prescribed Antipsychotics and Medication Adherence in Schizophrenia

Nagai Nobuhiro, Tani Hideaki, Suzuki Takefumi, Ikai Saeko, Gerretsen Philip, Mimura Masaru, Uchida Hiroyuki

Pharmacopsychiatry 2017

ISSN 0176-3679

Introduction Data on the knowledge about antipsychotic medications prescribed in patients with schizophrenia are very limited. Moreover, it remains unclear how patients’ knowledge about prescribed antipsychotics affects medication adherence. Methods ighty-one Japanese outpatients with schizophrenia according to the International Classification of Diseases, 10th edition, were included. Patients’ knowledge of the primary antipsychotics prescribed to them in terms of therapeutic effects, type, and implicated neurotransmitters was assessed with a multiple-choice questionnaire developed for this study. Medication possession ratios (MPRs) were compared between patients who answered correctly and those who did not in each category. Results The percentages of subjects who answered correctly regarding antipsychotic effects, type, and implicated neurotransmitters were low at 30.9%, 30.9%, and 7.4%, respectively. No differences were found in MPRs between subjects who answered correctly and those who did not. Discussion Our preliminary results indicate that patients lack knowledge about their antipsychotic medications. More concerning, they suggest that knowledge about prescribed antipsychotics may not directly translate into actual medication adherence in patients with schizophrenia.

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Threshold of dopamine D_2/3 receptor occupancy for hyperprolactinemia in older patients with schizophrenia

Iwata Yusuke, Nakajima Shinichiro, Caravaggio Fernando, Suzuki Takefumi, Uchida Hiroyuki, Plitman Eric, Chung Jun Ku, Mar Wanna, Gerretsen Philip, Pollock Bruce G., Mulsant Benoit H., Rajji Tarek K., Mamo David C., Graff-Guerrero Ariel

Journal of Clinical Psychiatry 77 ( 12 ) e1557 - e1563 2016.12

ISSN 0160-6689

Objective: Although hyperprolactinemia carries a long-Term risk of morbidity, the threshold of dopamine D2/3 receptor (D2/3R) occupancy for hyperprolactinemia has not been investigated in older patients with schizophrenia. Data were taken from a positron emission tomography (PET) study conducted between August 2007 and August 2015. The present post hoc study included 42 clinically stable outpatients with schizophrenia (DSM-IV) (mean SD age = 60.2 6.7 years) taking olanzapine or risperidone. Subjects underwent [11C]-raclopride PET scans to measure D2/3R occupancy before and after reducing their dose of antipsychotic by up to 40%. Blood samples were collected before each PET scan to measure prolactin levels. Methods: The relationship between prolactin levels and D_2/3R occupancy was examined using stepwise linear regression analyses. The D2/3R occupancy thresholds for hyperprolactinemia were explored using Fisher exact tests. Results: Prolactin levels decreased following dose reduction (mean SD = 24.1 30.2 ng/mL to 17.2 15.1 ng/mL; P < .001). Prolactin levels were associated with female gender (β = .32, P = .006, vs male), antipsychotics (β = .23, P = .02, risperidone vs olanzapine), and D_2/3R occupancy (β = .23, P = .04). Those with D_2/3R occupancy of 66% or higher were more likely to have hyperprolactinemia than those with D_2/3R occupancy lower than 66% (P = .03). Sensitivity, specificity, positive predictive value, and negative predictive value of this threshold were 0.44, 0.81, 0.78, and 0.48, respectively. We identified a D_2/3R occupancy threshold for hyperprolactinemia of 66% in older patients with schizophrenia, which is lower than that reported in younger patients (73%) by other researchers. Conclusions: Our results suggest a higher sensitivity to antipsychotics in older patients. Prolactin levels could assist in the determination of appropriate antipsychotic dosing to minimize adverse effects.

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Plasma levels and estimated dopamine D<inf>2</inf> receptor occupancy of long-acting injectable risperidone during maintenance treatment of schizophrenia: a 3-year follow-up study

Ikai S., Suzuki T., Mimura M., Uchida H.

Psychopharmacology (Psychopharmacology) 233 ( 23-24 ) 4003 - 4010 2016.12

ISSN 00333158

© 2016, Springer-Verlag Berlin Heidelberg. Introduction: Dopamine D2 receptor occupancy levels needed for the maintenance treatment of schizophrenia remain to be elucidated. We examined 3-year clinical outcomes of patients with schizophrenia who received long-acting injectable risperidone (LAI risperidone) at baseline and investigated their dopamine D2 receptor occupancy levels, estimated from plasma drug concentrations. Methods: A chart review of 52 outpatients with schizophrenia who participated in the original cross-sectional study was conducted to examine their 3-year clinical outcomes between April and September 2015. Patients who continued outpatient treatment with LAI risperidone without any usage of concomitant chlorpromazine equivalent antipsychotic dosage at >200 mg/day for the 3-year period were asked to participate in the follow-up assessments that included the Brief Psychiatric Rating Scale (BPRS) and estimated dopamine D2 receptor occupancy levels at trough, using plasma concentrations of risperidone plus 9-hydroxyrisperidone. Data were compared with the same patients collected 3 years earlier. Results: Among the original 52 participants, 14 participants (27 %) continued outpatient treatment with LAI risperidone. Ten participants (19 %) provided plasma samples; mean ± SD measured trough concentration of risperidone plus 9-hydroxyrisperidone significantly increased from 22.9 ± 15.6 to 31.8 ± 17.5 ng/mL (P = 0.02). Estimated dopamine D2 receptor occupancy numerically increased from 63.0 ± 10.9 to 69.0 ± 11.0 % (P = 0.12). A significant worsening was observed in the BPRS total score among these patients (mean ± SD, 34.3 ± 12.7 to 46.5 ± 16.9, P = 0.003). Conclusion: Paradoxically, the increased plasma concentration was found to be associated with a significant worsening of the clinical outcome. More investigations are indicated to shed further light on optimal levels of D2 blockade in the maintenance treatment of schizophrenia.

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Threshold of dopamine D<inf>2/3</inf> receptor occupancy for hyperprolactinemia in older patients with schizophrenia

Iwata Y., Nakajima S., Caravaggio F., Suzuki T., Uchida H., Plitman E., Chung J., Mar W., Gerretsen P., Pollock B., Mulsant B., Rajji T., Mamo D., Graff-Guerrero A.

Journal of Clinical Psychiatry (Journal of Clinical Psychiatry) 77 ( 12 ) e1557 - e1563 2016.12

ISSN 01606689

© Copyright 2016 Physicians Postgraduate Press, Inc. Objective: Although hyperprolactinemia carries a long-Term risk of morbidity, the threshold of dopamine D2/3 receptor (D2/3R) occupancy for hyperprolactinemia has not been investigated in older patients with schizophrenia. Data were taken from a positron emission tomography (PET) study conducted between August 2007 and August 2015. The present post hoc study included 42 clinically stable outpatients with schizophrenia (DSM-IV) (mean SD age = 60.2 6.7 years) taking olanzapine or risperidone. Subjects underwent [11C]-raclopride PET scans to measure D2/3R occupancy before and after reducing their dose of antipsychotic by up to 40%. Blood samples were collected before each PET scan to measure prolactin levels. Methods: The relationship between prolactin levels and D2/3R occupancy was examined using stepwise linear regression analyses. The D2/3R occupancy thresholds for hyperprolactinemia were explored using Fisher exact tests. Results: Prolactin levels decreased following dose reduction (mean SD = 24.1 30.2 ng/mL to 17.2 15.1 ng/mL; P < .001). Prolactin levels were associated with female gender (β = .32, P = .006, vs male), antipsychotics (β = .23, P = .02, risperidone vs olanzapine), and D2/3R occupancy (β = .23, P = .04). Those with D2/3R occupancy of 66% or higher were more likely to have hyperprolactinemia than those with D2/3R occupancy lower than 66% (P = .03). Sensitivity, specificity, positive predictive value, and negative predictive value of this threshold were 0.44, 0.81, 0.78, and 0.48, respectively. We identified a D2/3R occupancy threshold for hyperprolactinemia of 66% in older patients with schizophrenia, which is lower than that reported in younger patients (73%) by other researchers. Conclusions: Our results suggest a higher sensitivity to antipsychotics in older patients. Prolactin levels could assist in the determination of appropriate antipsychotic dosing to minimize adverse effects.

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Gic1 is a novel heterochromatin boundary protein in vivo.

Mitsumori R, Shinmyozu K, Nakayama JI, Uchida H, Oki M

Genes & genetic systems 91 ( 3 ) 151 - 159 2016.11

ISSN 1341-7568

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Quality of life in stabilized patients with schizophrenia is mainly associated with resilience and self-esteem

Wartelsteiner F., Mizuno Y., Frajo-Apor B., Kemmler G., Pardeller S., Sondermann C., Welte A., Fleischhacker W. W., Uchida H., Hofer A.

Acta Psychiatrica Scandinavica (Acta Psychiatrica Scandinavica) 134 ( 4 ) 360 - 367 2016.10

ISSN 0001-690X

Objective: Improving quality of life (QoL) is an important objective in the treatment of schizophrenia. The aim of the current study was to examine to what extent resilience, self-esteem, hopelessness, and psychopathology are correlated with QoL. Method: We recruited 52 out-patients diagnosed with schizophrenia according to DSM-IV criteria and 77 healthy control subjects from the general community. In patients, psychopathology was quantified by the Positive and Negative Syndrome Scale. The following scales were used in both patients and control subjects: the Berliner Lebensqualitätsprofil, the Resilience Scale, the Rosenberg Self-Esteem Scale, and the Beck Hopelessness Scale to assess QoL, resilience, self-esteem, and hopelessness respectively. Results: Patients with schizophrenia presented with significantly less QoL, resilience, self-esteem, and hope compared to healthy control subjects. In patients, QoL correlated moderately with resilience, self-esteem, and hopelessness and weakly with symptoms. With respect to the latter, particularly depression and positive symptoms were negatively correlated with QoL. Conclusion: Our results highlight the complex nature of QoL in patients suffering from schizophrenia. They underscore that significant efforts are necessary to enhance resilience and self-esteem and to diminish hopelessness as well as affective and positive symptoms in patients with schizophrenia.

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Erratum

Yoshida Kazunari, Suzuki Takefumi, Imasaka Yasushi, Kubo Ken ichiro, Mizuno Yuya, Saruta Juri, Tsukinoki Keiichi, Mimura Masaru, Uchida Hiroyuki

Schizophrenia Research 176 ( 2-3 ) 580 2016.10

ISSN 0920-9964

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Increasing versus maintaining the dose of olanzapine or risperidone in schizophrenia patients who did not respond to a modest dosage

Sakurai Hitoshi, Suzuki Takefumi, Bies Robert R., Pollock Bruce G., Mimura Masaru, Kapur Shitij, Uchida Hiroyuki

Journal of Clinical Psychiatry 77 ( 10 ) 1381 - 1390 2016.10

ISSN 0160-6689

Objective: While doctors often increase the dose of an antipsychotic when there is insufficient response, there is limited evidence that this intervention is any better than waiting longer on the lower dose. We put the proposition to test. Method: In this 4-week, double-blind, randomized controlled trial conducted in psychiatric care from September 2012 to March 2015, 103 patients with schizophrenia (ICD-10) who did not respond to olanzapine 10 mg/d or risperidone 3 mg/d were randomly allocated to a dose-increment or -continuation group. In the increment group, antipsychotic doses were doubled for 4 weeks, whereas in the continuation group, doses were not changed. Completion rate (primary outcome measure); changes in psychopathology, function, and extrapyramidal symptoms; and response rate were compared between the groups. The relationship between baseline plasma antipsychotic concentrations and changes in psychopathology was examined. Results: The completion rate was significantly lower in the increment group than in the continuation group (69.2% [36/52] vs 86.3% [44/51], P = .038). No significant superiority was observed in any of the outcome measures in the increment group compared to the continuation group, except the Positive and Negative Syndrome Scale (PANSS) positive subscale score change in intentionto- treat analysis. Those with lower plasma concentrations of olanzapine on their initial treatment showed a greater improvement on the PANSS positive subscale when their dose was increased (P = .042). Conclusions: As a general strategy, patients with schizophrenia failing to respond to moderate antipsychotic doses may not benefit from an increase in dose. The possibility of benefit in those whose plasma antipsychotic concentrations at baseline are still low cannot be ruled out. Trial Registration: UMIN.ac.jp/ctr/index.htm identifier: UMIN000008667.

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Four domains of Ada1 form a heterochromatin boundary through different mechanisms.

Kamata K, Shinmyozu K, Nakayama JI, Hatashita M, Uchida H, Oki M

Genes to cells : devoted to molecular & cellular mechanisms 21 ( 10 ) 1125 - 1136 2016.10

ISSN 1356-9597

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Increasing versus maintaining the dose of olanzapine or risperidone in schizophrenia patients who did not respond to a modest dosage: A double-blind randomized controlled trial

Sakurai H., Suzuki T., Bies R., Pollock B., Mimura M., Kapur S., Uchida H.

Journal of Clinical Psychiatry (Journal of Clinical Psychiatry) 77 ( 10 ) 1381 - 1390 2016.10

ISSN 01606689

© Copyright 2016 Physicians Postgraduate Press, Inc. Objective: While doctors often increase the dose of an antipsychotic when there is insufficient response, there is limited evidence that this intervention is any better than waiting longer on the lower dose. We put the proposition to test. Method: In this 4-week, double-blind, randomized controlled trial conducted in psychiatric care from September 2012 to March 2015, 103 patients with schizophrenia (ICD-10) who did not respond to olanzapine 10 mg/d or risperidone 3 mg/d were randomly allocated to a dose-increment or -continuation group. In the increment group, antipsychotic doses were doubled for 4 weeks, whereas in the continuation group, doses were not changed. Completion rate (primary outcome measure); changes in psychopathology, function, and extrapyramidal symptoms; and response rate were compared between the groups. The relationship between baseline plasma antipsychotic concentrations and changes in psychopathology was examined. Results: The completion rate was significantly lower in the increment group than in the continuation group (69.2% [36/52] vs 86.3% [44/51], P = .038). No significant superiority was observed in any of the outcome measures in the increment group compared to the continuation group, except the Positive and Negative Syndrome Scale (PANSS) positive subscale score change in intentionto- treat analysis. Those with lower plasma concentrations of olanzapine on their initial treatment showed a greater improvement on the PANSS positive subscale when their dose was increased (P = .042). Conclusions: As a general strategy, patients with schizophrenia failing to respond to moderate antipsychotic doses may not benefit from an increase in dose. The possibility of benefit in those whose plasma antipsychotic concentrations at baseline are still low cannot be ruled out. Trial Registration: UMIN.ac.jp/ctr/index.htm identifier: UMIN000008667.

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Lack of Early Improvement with Antipsychotics is a Marker for Subsequent Nonresponse in Behavioral and Psychological Symptoms of Dementia

Yoshida Kazunari, Roberts Rachel, Suzuki Takefumi, Lebowitz Barry, Reeves Suzanne, Howard Robert, Abe Takayuki, Mimura Masaru, Uchida Hiroyuki

American Journal of Geriatric Psychiatry 2016.09

ISSN 1064-7481

Objective: Prediction of response or nonresponse to antipsychotics is especially important in patients with behavioral and psychological symptoms of dementia (BPSD) in whom antipsychotic exposure increases risks of death. This study examined whether the presence or absence of early improvement of BPSD with antipsychotics is associated with subsequent response or nonresponse. Methods: In a post-hoc analysis of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) study (2001-2004) (clinicaltrials.gov; NCT00015548) in 45 U.S. sites, 245 subjects (olanzapine, N = 90; quetiapine, N = 81; risperidone, N = 74) with a DSM-IV diagnosis of dementia of the Alzheimer type who presented with a score of 1 or more in the Brief Psychiatric Rating Scale (BPRS) at baseline (phase I of CATIE-AD) were randomly assigned to treatment with olanzapine, quetiapine, risperidone, or placebo in a double-blind manner. Associations were examined between response at week 8 and demographic and clinical characteristics, including BPRS total score reduction at week 2, using logistic regression analyses. Prediction performance of binary classification (presence or absence) of improvement or no improvement at week 2 for response at week 8 was examined. Results: BPRS total score reduction at week 2 (mean percentage score reduction: 12.6%) was significantly associated with response at week 8 (odds ratio: 1.18; 95% CI: 1.11-1.26). The 5% score reduction cut-off at week 2 showed the highest accuracy (0.71), with sensitivity, specificity, and positive and negative predictivevalues of 0.76, 0.65, 0.69, and 0.72, respectively. Conclusion: Lack of even a very small early improvement with antipsychotic treatment may be a marker of subsequent nonresponse in BPSD.

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Plasma levels and estimated dopamine D₂ receptor occupancy of long-acting injectable risperidone during maintenance treatment of schizophrenia

Ikai Saeko, Suzuki Takefumi, Mimura Masaru, Uchida Hiroyuki

Psychopharmacology 1 - 8 2016.09

ISSN 0033-3158

Introduction: Dopamine D₂ receptor occupancy levels needed for the maintenance treatment of schizophrenia remain to be elucidated. We examined 3-year clinical outcomes of patients with schizophrenia who received long-acting injectable risperidone (LAI risperidone) at baseline and investigated their dopamine D₂ receptor occupancy levels, estimated from plasma drug concentrations. Methods: A chart review of 52 outpatients with schizophrenia who participated in the original cross-sectional study was conducted to examine their 3-year clinical outcomes between April and September 2015. Patients who continued outpatient treatment with LAI risperidone without any usage of concomitant chlorpromazine equivalent antipsychotic dosage at >200 mg/day for the 3-year period were asked to participate in the follow-up assessments that included the Brief Psychiatric Rating Scale (BPRS) and estimated dopamine D₂ receptor occupancy levels at trough, using plasma concentrations of risperidone plus 9-hydroxyrisperidone. Data were compared with the same patients collected 3 years earlier. Results: Among the original 52 participants, 14 participants (27 %) continued outpatient treatment with LAI risperidone. Ten participants (19 %) provided plasma samples; mean ± SD measured trough concentration of risperidone plus 9-hydroxyrisperidone significantly increased from 22.9 ± 15.6 to 31.8 ± 17.5 ng/mL (P = 0.02). Estimated dopamine D₂ receptor occupancy numerically increased from 63.0 ± 10.9 to 69.0 ± 11.0 % (P = 0.12). A significant worsening was observed in the BPRS total score among these patients (mean ± SD, 34.3 ± 12.7 to 46.5 ± 16.9, P = 0.003). Conclusion: Paradoxically, the increased plasma concentration was found to be associated with a significant worsening of the clinical outcome. More investigations are indicated to shed further light on optimal levels of D₂ blockade in the maintenance treatment of schizophrenia.

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