研究者詳細 - 内田　裕之

論文 - 内田　裕之

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Discrepancy in psychological attitudes toward living donor liver transplantation between recipients and donors

Hayashi K., Uchida H., Takaoka C., Izawa Y., Shinoda M., Obara H., Itano O., Shirahase J., Tanabe M., Kitagawa Y., Mimura M.

Transplantation （Transplantation） 99 （ 12 ） 2551 - 2555 2015年

ISSN 0041-1337

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Background. Mutual understanding between recipients and donors is indispensable when living donor liver transplantation (LDLT) is performed, which, however, has gained little attention and remains unaddressed in the literature. Methods. Fiftyseven pairs, a recipient (mean ± SD age at the operation, 48.3 ± 10.6 years; mean ± SD years after the operation, 6.2 ± 4.7 years) and his or her donor, who underwent LDLT completed a 13-item questionnaire on a 7-point Likert scale (1: strongly agree to 7: strongly disagree) that was designed to assess for their psychological attitudes toward transplantation. They were also asked to estimate their donor's or recipient's response to the questionnaire, respectively. Values of interest were compared between groups, using paired t tests. Following Bonferroni correction, a P value less than 0.0038 (0.05/13) was considered statistically significant. Results. Significant differences were observed between actually answered and estimated responses in 7 of the 13 items in the questionnaire for donors. For example, donors did not feel pressure to become a donor to the same degree as their recipients estimated (4.6 ± 1.9 vs 3.4 ± 1.8). In contrast, only 1 item showed a significant difference between actually answered and estimated responses in the questionnaire for recipients; recipients did not worry about the transplanted liver compared to their donors' estimation (3.1 ± 1.9 vs 2.1 ± 0.8). Conclusions. Recipients did not fully understand the donors' feelings toward LDLT, whereas donors almost correctly understood their recipients' attitudes. Our findings clearly revealed the gap in their mutual understanding and emphasize the need of psychological education to bridge the gap.

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[A Proposal for Natural Resilience Theory in Psychopharmacotherapy: To Deter High-dose Antipsychotic Polypharmacy].

Yagi G, Suzuki T, Uchida H

Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica 117 （ 1 ） 10 - 7 2015年

ISSN 0033-2658

A Proposal for Natural Resilience Theory in Psychopharmacotherapy: To Deter High-dose Antipsychotic Polypharmacy

Yagi G., Suzuki T., Uchida H.

Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica （Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica） 117 （ 1 ） 10 - 17 2015年

ISSN 00332658

Successful withdrawal from antipsychotic treatment in elderly male inpatients with schizophrenia-Description of four cases and review of the literature

Suzuki T., Uchida H.

Psychiatry Research （Psychiatry Research） 220 （ 1-2 ） 152 - 157 2014年12月

ISSN 0165-1781

© 2014 Elsevier Ireland Ltd. We describe four elderly male inpatients with chronic schizophrenia successfully withdrawn from long-lasting antipsychotic treatment. Then we review studies in which antipsychotics were discontinued in patients 65 y.o. (or at least 50 on the average) or older using PubMed (last search; August 2014). The average (±S.D.) age, duration of illness and total duration of hospitalization of the patients were 77.0±8.6 y.o., 46.0±26.9 years, and 41.0±27.3 years, respectively. Illness severity as assessed with the Clinical Global Impression (CGI)-Severity was five for three patients and six for the other. After withdrawal from antipsychotic treatment for 28.3±11.4 weeks, none showed appreciable changes in psychopathology, functioning as well as adverse effects and the resultant CGI-Improvement was four for all patients. Compared with those who needed continuous antipsychotic treatment in the same unit (n=51; mean±S.D. age: 56.0±12.1 y.o.), they were significantly older and treated with a fewer number of total psychotropics at baseline (1.50±1.00 versus 4.94±1.93 agents). A literature search failed to find any studies in which antipsychotics were discontinued exclusively in patients with schizophrenia 65 years or older and underscored a clear paucity of data on this important topic. Cessation of chronic antipsychotic treatment could be a viable option at least in some patients with geriatric schizophrenia although more systematic studies are necessary.

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Dose and dosing frequency of long-acting injectable antipsychotics a systematic review of PET and SPECT data and clinical implications

Uchida H., Suzuki T.

Journal of Clinical Psychopharmacology （Journal of Clinical Psychopharmacology） 34 （ 6 ） 728 - 735 2014年12月

ISSN 0271-0749

Copyright © 2014 Lippincott Williams & Wilkins. Brain imaging data of antipsychotics have mainly been derived from oral antipsychotic drugs, which hampers our understanding of the requirement of dose/dosing frequency of long-acting injectable (LAI) antipsychotics for the maintenance treatment of schizophrenia. A systematic literature search was performed to identify positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies that assessed dopamine D2 receptor occupancy levels with LAI antipsychotic drugs in humans, using PubMed, EMBASE, and PsycINFO (last search, February 2013). Twenty studies (15 PET and 5 SPECT studies) were identified. The most investigated drug in these PET and SPECT studies was haloperidol decanoate (44 subjects; 11 studies), followed by risperidone LAI (24 subjects; 3 studies), olanzapine pamoate (14 subject; 1 study), and fluphenazine decanoate (12 subjects; 3 studies). The data have demonstrated high and continuous D2 receptor blockade with LAIs; the effects of LAI first-generation antipsychotics on the central nervous system may persist for several months. The prospective and cross-sectional studies showed that continuous dopamine D2 receptor blockade above 65% (ie, the lower end of the established therapeutic window for the acute phase treatment) was not always necessary for maintenance treatment for at least some of the patients. In conclusion, because of the limited brain imaging data on LAI antipsychotics, we still do not know the best way to dose them. Still, the currently available brain imaging data raises a possibility that the dosing interval of LAI antipsychotics may be extended beyond the currently indicated range in some patients.

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Prophylactic use of heparin for deep vein thrombosis in restrained psychiatric patients

Ishida Takuto, Suzuki Takefumi, Watanabe Koichiro, Sakurai Hitoshi, Uchida Hiroyuki, Mimura Masaru

General Hospital Psychiatry 36 （ 6 ） 690 - 693 2014年11月

ISSN 0163-8343

Objective: Physical restraint sometimes causes deep vein thrombosis (DVT) and pulmonary embolism. Although unfractionated heparin (UFH) is used for the prophylaxis of DVT, its effectiveness remained unknown for restrained patients. Method: We conducted a chart review of restrained inpatients at Sakuragaoka Memorial Hospital in Japan. Restrained patients received subcutaneous injection of UFH 5000 IU bid from December 2008 to September 2010 [heparin (+) period] while UFH was not used from December 2010 to September 2012 [heparin (-) period]. A Doppler ultrasound scanning was performed to examine the presence of DVT. The incidence of DVT was compared between the two periods by chi-square test. A multiple logistic regression model was used to examine effects of demographic and clinical characteristics on the incidence of DVT. Results: No significant difference was found in the incidence of DVT between the heparin (+) and (-) periods [11.8% (11/93) vs. 11.1% (13/117)]. Sedation [odds ratio (OR)=3.78], physical comorbidities (OR=6.29) and a longer duration of restraint (OR=1.22) were associated with the incidence of DVT. Conclusion: The use of UFH was not associated with any reduction in the incidence of DVT in restrained psychiatric patients.

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Dose reduction of risperidone and olanzapine and estimated dopamine D<inf>2</inf> receptor occupancy in stable patients with schizophrenia

Takeuchi Hiroyoshi, Suzuki Takefumi, Bies Robert R., Remington Gary, Watanabe Koichiro, Mimura Masaru, Uchida Hiroyuki

Journal of Clinical Psychiatry 75 （ 11 ） 1209 - 1214 2014年11月

ISSN 0160-6689

Background: While acute-phase antipsychotic response has been attributed to 65%-80% dopamine D<inf>2</inf> receptor blockade, the degree of occupancy for relapse prevention in the maintenance treatment of schizophrenia remains unknown. Method: In this secondary study of an open-label, 28-week, randomized, controlled trial conducted between April 2009 and August 2011, clinically stable patients with schizophrenia (DSM-IV) treated with risperidone or olanzapine were randomly assigned to the reduction group (dose reduced by 50%) or maintenance group (dose kept constant). Plasma antipsychotic concentrations at peak and trough before and after dose reduction were estimated with population pharmacokinetic techniques, using 2 collected plasma samples. Corresponding dopamine D<inf>2</inf> occupancy levels were then estimated using the model we developed. Relapse was defined as worsening in 4 Positive and Negative Syndrome Scale-Positive subscale items: delusion, conceptual disorganization, hallucinatory behavior, and suspiciousness. Results: Plasma antipsychotic concentrations were available for 16 and 15 patients in the reduction and maintenance groups, respectively. Estimated dopamine D<inf>2</inf> occupancy (mean ± SD) decreased following dose reduction from 75.6% ± 4.9% to 66.8% ± 6.4% at peak and 72.3% ± 5.7% to 62.0% ± 6.8% at trough. In the reduction group, 10 patients (62.5%) did not demonstrate continuous D<inf>2</inf> receptor blockade above 65% (ie, < 65% at trough) after dose reduction; furthermore, 7 patients (43.8%) did not achieve a threshold of 65% occupancy even at peak. Nonetheless, only 1 patient met our relapse criteria after dose reduction during the 6 months of the study. Conclusions: The results suggest that the therapeutic threshold regarding dopamine D<inf>2</inf> occupancy may be lower for those who are stable in antipsychotic maintenance versus acute-phase treatment. Positron emission tomography studies are warranted to further test our preliminary findings.

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Effects of weekly one-hour hatha yoga therapy on resilience and stress levels in patients with schizophrenia-spectrum disorders

Ikai Saeko, Suzuki Takefumi, Uchida Hiroyuki, Saruta Juri, Tsukinoki Keiichi, Fujii Yasuo, Mimura Masaru

Journal of Alternative and Complementary Medicine 20 （ 11 ） 823 - 830 2014年11月

ISSN 1075-5535

Objective: To examine the effects of Hatha yoga therapy on resilience, brain-derived neurotrophic factor (BDNF) levels, and salivary alpha amylase (SAA) activity in patients with schizophrenia-spectrum disorders. Design and participants: Single-blinded, randomized controlled study in which outpatients with schizophrenia or related psychotic disorders (according to International Classification of Diseases, 10th Revision) were randomly assigned to a yoga or a control group. Setting: November 2012-April 2013 at Yamanashi Prefectural Kita Hospital, Japan. Interventions: In the yoga group, patients received weekly 1-hour Hatha yoga sessions, in addition to regular treatment, for 8 weeks. Those in the control group underwent regular treatment, which included a daycare rehabilitation program. Outcome measures: Assessments included the 25-item Resilience Scale (RS), Positive and Negative Syndrome Scale (PANSS), plasma and salivary BDNF level, and SAA activity. Results: Fifty patients participated (25 in each group; mean age±standard deviation, 50.9±11.3 years; mean duration of illness, 25.0±10.3 years; mean total PANSS score, 78.2±17.3). No significant differences in changes in any variable from baseline to week 8 were found between the two groups (changes in the yoga group versus the control group: RS score, -1.6±19.9 versus 0.3±17.2; PANSS score, 0.5±12.0 versus 5.0±15.6; plasma BDNF, 41.6±377.0âpg/dl versus 73.4±346.0â€‰pg/dl; SAA, -26.2±72.6â€‰kU/l versus -13.8±68.0â€‰kU/l, respectively). Conclusions: Adjunct yoga therapy showed no positive changes in resilience level or stress markers. Duration and intensity of yoga sessions and the focus on patients with chronic illness may explain the negative observations in light of past positive evidence regarding yoga therapy.

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Pharmacological strategies to counteract antipsychotic-induced weight gain and metabolic adverse effects in schizophrenia

Mizuno Yuya, Suzuki Takefumi, Nakagawa Atsuo, Yoshida Kazunari, Mimura Masaru, Fleischhacker Walter Wolfgang, Uchida Hiroyuki

Schizophrenia Bulletin 40 （ 6 ） 1385 - 1403 2014年11月

ISSN 0586-7614

Background: Antipsychotic-induced metabolic adversities are often difficult to manage. Using concomitant medications to counteract these adversities may be a rational option. Objective: To systematically determine the effectiveness of medications to counteract antipsychotic-induced metabolic adversities in patients with schizophrenia. Data Sources: Published articles until November 2013 were searched using 5 electronic databases. Clinical trial registries were searched for unpublished trials. Study Selection: Double-blind randomized placebo-controlled trials focusing on patients with schizophrenia were included if they evaluated the effects of concomitant medications on antipsychotic-induced metabolic adversities as a primary outcome. Data Extraction: Variables relating to participants, interventions, comparisons, outcomes, and study design were extracted. The primary outcome was change in body weight. Secondary outcomes included clinically relevant weight change, fasting glucose, hemoglobin A1c, fasting insulin, insulin resistance, cholesterol, and triglycerides. Data Synthesis: Forty trials representing 19 unique interventions were included in this meta-analysis. Metformin was the most extensively studied drug in regard to body weight, the mean difference amounting to -3.17 kg (95% CI: -4.44 to -1.90 kg) compared to placebo. Pooled effects for topiramate, sibutramine, aripiprazole, and reboxetine were also different from placebo. Furthermore, metformin and rosiglitazone improved insulin resistance, while aripiprazole, metformin, and sibutramine decreased blood lipids. Conclusion: When nonpharmacological strategies alone are insufficient, and switching antipsychotics to relatively weight-neutral agents is not feasible, the literature supports the use of concomitant metformin as first choice among pharmacological interventions to counteract antipsychotic-induced weight gain and other metabolic adversities in schizophrenia.

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Dose reduction of risperidone and olanzapine and estimated dopamine D<inf>2</inf> receptor occupancy in stable patients with schizophrenia: Findings from an open-label, randomized, controlled study

Takeuchi H., Suzuki T., Bies R., Remington G., Watanabe K., Mimura M., Uchida H.

Journal of Clinical Psychiatry （Journal of Clinical Psychiatry） 75 （ 11 ） 1209 - 1214 2014年11月

ISSN 01606689

© Copyright 2014 Physicians Postgraduate Press, Inc. Background: While acute-phase antipsychotic response has been attributed to 65%-80% dopamine D2 receptor blockade, the degree of occupancy for relapse prevention in the maintenance treatment of schizophrenia remains unknown. Method: In this secondary study of an open-label, 28-week, randomized, controlled trial conducted between April 2009 and August 2011, clinically stable patients with schizophrenia (DSM-IV) treated with risperidone or olanzapine were randomly assigned to the reduction group (dose reduced by 50%) or maintenance group (dose kept constant). Plasma antipsychotic concentrations at peak and trough before and after dose reduction were estimated with population pharmacokinetic techniques, using 2 collected plasma samples. Corresponding dopamine D2 occupancy levels were then estimated using the model we developed. Relapse was defined as worsening in 4 Positive and Negative Syndrome Scale-Positive subscale items: delusion, conceptual disorganization, hallucinatory behavior, and suspiciousness. Results: Plasma antipsychotic concentrations were available for 16 and 15 patients in the reduction and maintenance groups, respectively. Estimated dopamine D2 occupancy (mean ± SD) decreased following dose reduction from 75.6% ± 4.9% to 66.8% ± 6.4% at peak and 72.3% ± 5.7% to 62.0% ± 6.8% at trough. In the reduction group, 10 patients (62.5%) did not demonstrate continuous D2 receptor blockade above 65% (ie, < 65% at trough) after dose reduction; furthermore, 7 patients (43.8%) did not achieve a threshold of 65% occupancy even at peak. Nonetheless, only 1 patient met our relapse criteria after dose reduction during the 6 months of the study. Conclusions: The results suggest that the therapeutic threshold regarding dopamine D2 occupancy may be lower for those who are stable in antipsychotic maintenance versus acute-phase treatment. Positron emission tomography studies are warranted to further test our preliminary findings.

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Effects of weekly one-hour hatha yoga therapy on resilience and stress levels in patients with schizophrenia-spectrum disorders: An eight-week randomized controlled trial

Ikai S., Suzuki T., Uchida H., Saruta J., Tsukinoki K., Fujii Y., Mimura M.

Journal of Alternative and Complementary Medicine （Journal of Alternative and Complementary Medicine） 20 （ 11 ） 823 - 830 2014年11月

ISSN 10755535

© 2014, Mary Ann Liebert, Inc. Objective: To examine the effects of Hatha yoga therapy on resilience, brain-derived neurotrophic factor (BDNF) levels, and salivary alpha amylase (SAA) activity in patients with schizophrenia-spectrum disorders. Design and participants: Single-blinded, randomized controlled study in which outpatients with schizophrenia or related psychotic disorders (according to International Classification of Diseases, 10th Revision) were randomly assigned to a yoga or a control group. Setting: November 2012-April 2013 at Yamanashi Prefectural Kita Hospital, Japan. Interventions: In the yoga group, patients received weekly 1-hour Hatha yoga sessions, in addition to regular treatment, for 8 weeks. Those in the control group underwent regular treatment, which included a daycare rehabilitation program. Outcome measures: Assessments included the 25-item Resilience Scale (RS), Positive and Negative Syndrome Scale (PANSS), plasma and salivary BDNF level, and SAA activity. Results: Fifty patients participated (25 in each group; mean age±standard deviation, 50.9±11.3 years; mean duration of illness, 25.0±10.3 years; mean total PANSS score, 78.2±17.3). No significant differences in changes in any variable from baseline to week 8 were found between the two groups (changes in the yoga group versus the control group: RS score, -1.6±19.9 versus 0.3±17.2; PANSS score, 0.5±12.0 versus 5.0±15.6; plasma BDNF, 41.6±377.0âpg/dl versus 73.4±346.0â€‰pg/dl; SAA, -26.2±72.6â€‰kU/l versus -13.8±68.0â€‰kU/l, respectively). Conclusions: Adjunct yoga therapy showed no positive changes in resilience level or stress markers. Duration and intensity of yoga sessions and the focus on patients with chronic illness may explain the negative observations in light of past positive evidence regarding yoga therapy.

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Pharmacological strategies to counteract antipsychotic-induced weight gain and metabolic adverse effects in schizophrenia: A systematic review and meta-analysis

Mizuno Y., Suzuki T., Nakagawa A., Yoshida K., Mimura M., Fleischhacker W., Uchida H.

Schizophrenia Bulletin （Schizophrenia Bulletin） 40 （ 6 ） 1385 - 1403 2014年11月

ISSN 05867614

© 2014 © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. Background: Antipsychotic-induced metabolic adversities are often difficult to manage. Using concomitant medications to counteract these adversities may be a rational option. Objective: To systematically determine the effectiveness of medications to counteract antipsychotic-induced metabolic adversities in patients with schizophrenia. Data Sources: Published articles until November 2013 were searched using 5 electronic databases. Clinical trial registries were searched for unpublished trials. Study Selection: Double-blind randomized placebo-controlled trials focusing on patients with schizophrenia were included if they evaluated the effects of concomitant medications on antipsychotic-induced metabolic adversities as a primary outcome. Data Extraction: Variables relating to participants, interventions, comparisons, outcomes, and study design were extracted. The primary outcome was change in body weight. Secondary outcomes included clinically relevant weight change, fasting glucose, hemoglobin A1c, fasting insulin, insulin resistance, cholesterol, and triglycerides. Data Synthesis: Forty trials representing 19 unique interventions were included in this meta-analysis. Metformin was the most extensively studied drug in regard to body weight, the mean difference amounting to -3.17 kg (95% CI: -4.44 to -1.90 kg) compared to placebo. Pooled effects for topiramate, sibutramine, aripiprazole, and reboxetine were also different from placebo. Furthermore, metformin and rosiglitazone improved insulin resistance, while aripiprazole, metformin, and sibutramine decreased blood lipids. Conclusion: When nonpharmacological strategies alone are insufficient, and switching antipsychotics to relatively weight-neutral agents is not feasible, the literature supports the use of concomitant metformin as first choice among pharmacological interventions to counteract antipsychotic-induced weight gain and other metabolic adversities in schizophrenia.

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Prophylactic use of heparin for deep vein thrombosis in restrained psychiatric patients: A chart review

Ishida T., Suzuki T., Watanabe K., Sakurai H., Uchida H., Mimura M.

General Hospital Psychiatry （General Hospital Psychiatry） 36 （ 6 ） 690 - 693 2014年11月

ISSN 01638343

© 2014 Elsevier Inc. Objective: Physical restraint sometimes causes deep vein thrombosis (DVT) and pulmonary embolism. Although unfractionated heparin (UFH) is used for the prophylaxis of DVT, its effectiveness remained unknown for restrained patients. Method: We conducted a chart review of restrained inpatients at Sakuragaoka Memorial Hospital in Japan. Restrained patients received subcutaneous injection of UFH 5000 IU bid from December 2008 to September 2010 [heparin (+) period] while UFH was not used from December 2010 to September 2012 [heparin (-) period]. A Doppler ultrasound scanning was performed to examine the presence of DVT. The incidence of DVT was compared between the two periods by chi-square test. A multiple logistic regression model was used to examine effects of demographic and clinical characteristics on the incidence of DVT. Results: No significant difference was found in the incidence of DVT between the heparin (+) and (-) periods [11.8% (11/93) vs. 11.1% (13/117)]. Sedation [odds ratio (OR)=3.78], physical comorbidities (OR=6.29) and a longer duration of restraint (OR=1.22) were associated with the incidence of DVT. Conclusion: The use of UFH was not associated with any reduction in the incidence of DVT in restrained psychiatric patients.

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Timing of Adjunctive Therapy in the Treatment of Depression

Tarumi R., Suzuki T., Tani H., Den R., Sawada N., Sakurai H., Tsutsumi-Ozawa C., Ohtani A., Mimura M., Uchida H.

Pharmacopsychiatry 47 （ 7 ） 259 - 262 2014年10月

ISSN 0176-3679

Introduction: The objective of this study was to examine the evolution of antidepressant switch and adjunctive therapy. Methods: This chart review was conducted at 6 primary psychiatric clinics or hospitals, in Tokyo, Japan. A chart review of longitudinal prescriptions was conducted regarding 633 outpatients with major depressive disorder for up to 2 years after their first visit. Patients who had already received antidepressants prior to the visit were excluded. Results: 22.6% (N=143) of the patients completed or continued the outpatient treatment over the 2 years while 27 (4.3%), 23 (3.6%), and 439 (69.4%) patients discontinued it due to hospitalization, referral to another clinic, and loss to follow-up, respectively. A total of 597 episodes of antidepressant treatment were identified. Among them, 482 episodes (80.7%) were associated with the suggested dose ranges while antidepressant drugs were under-dosed in 19.3% (N=115) of the episodes. 50 patients (7.9%) received adjunctive therapy; it was employed after a median of only one antidepressant had been tried. Conclusion: Psychiatrists may be hasty in prescribing an adjunctive therapy in the treatment of depression.

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Timing of Adjunctive Therapy in the Treatment of Depression: A Chart Review

Tarumi R., Suzuki T., Tani H., Den R., Sawada N., Sakurai H., Tsutsumi-Ozawa C., Ohtani A., Mimura M., Uchida H.

Pharmacopsychiatry （Pharmacopsychiatry） 47 （ 7 ） 259 - 262 2014年10月

ISSN 01763679

© Georg Thieme Verlag KG. Introduction: The objective of this study was to examine the evolution of antidepressant switch and adjunctive therapy. Methods: This chart review was conducted at 6 primary psychiatric clinics or hospitals, in Tokyo, Japan. A chart review of longitudinal prescriptions was conducted regarding 633 outpatients with major depressive disorder for up to 2 years after their first visit. Patients who had already received antidepressants prior to the visit were excluded. Results: 22.6% (N=143) of the patients completed or continued the outpatient treatment over the 2 years while 27 (4.3%), 23 (3.6%), and 439 (69.4%) patients discontinued it due to hospitalization, referral to another clinic, and loss to follow-up, respectively. A total of 597 episodes of antidepressant treatment were identified. Among them, 482 episodes (80.7%) were associated with the suggested dose ranges while antidepressant drugs were under-dosed in 19.3% (N=115) of the episodes. 50 patients (7.9%) received adjunctive therapy; it was employed after a median of only one antidepressant had been tried. Conclusion: Psychiatrists may be hasty in prescribing an adjunctive therapy in the treatment of depression.

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Therapeutic window for striatal dopamine D_2/3 receptor occupancy in older patients with schizophrenia

Uchida Hiroyuki, Suzuki Takefumi, Graff-Guerrero Ariel, Mulsant Benoit H., Pollock Bruce G., Arenovich Tamara, Rajji Tarek K., Mamo David C.

American Journal of Geriatric Psychiatry 22 （ 10 ） 1007 - 1016 2014年10月

ISSN 1064-7481

Objective In younger patients with schizophrenia, positron emission tomography (PET) studies have identified a therapeutic window of striatal dopamine D_2/3 receptor occupancy of 65%-80%. This type of empirical information is not available in late life. Our primary aim was to assess the effect of changes in D_2/3 relative receptor occupancy (RRO) on clinical outcomes in this population. Design Open-label intervention. Setting Centre for Addiction and Mental Health, Toronto. Participants Subjects with schizophrenia age 50 years or more who were clinically stable and previously maintained on oral risperidone for more than 6 months. Intervention A dose reduction of risperidone of up to 40%, followed by a 3-month follow-up. Measurements Dopamine D_2/3 RRO in dorsal putamen was assessed, using the region of interest analysis of [¹¹C]raclopride PET scans, before and after the dose reduction. Clinical assessments included the Positive and Negative Syndrome Scale and the Simpson-Angus Scale. Results Nine subjects (mean ± SD age: 58 ± 7 years; mean ± SD baseline risperidone dose: 3.4 ± 1.6 mg/day) participated in the study. Extrapyramidal symptoms (EPS) were present in six subjects and were associated with 70% or more D_2/3 RRO in the putamen (range: 70%-87%). Following the dose reduction, EPS resolved in five subjects. Two subjects experienced a clinical worsening at 52% and at less than 50% D_2/3 RRO. Conclusion EPS diminished less than 70% D_2/3 RRO, which suggests a lower therapeutic window for older patients with schizophrenia than that for younger patients. Although these findings have to be replicated in a larger sample, they have important implications for future drug development and clinical guidelines in late-life schizophrenia.

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Therapeutic window for striatal dopamine D<inf>2/3</inf> receptor occupancy in older patients with schizophrenia: A pilot PET study

Uchida H., Suzuki T., Graff-Guerrero A., Mulsant B., Pollock B., Arenovich T., Rajji T., Mamo D.

American Journal of Geriatric Psychiatry （American Journal of Geriatric Psychiatry） 22 （ 10 ） 1007 - 1016 2014年10月

ISSN 10647481

© 2014 American Association for Geriatric Psychiatry. Objective In younger patients with schizophrenia, positron emission tomography (PET) studies have identified a therapeutic window of striatal dopamine D2/3 receptor occupancy of 65%-80%. This type of empirical information is not available in late life. Our primary aim was to assess the effect of changes in D2/3 relative receptor occupancy (RRO) on clinical outcomes in this population. Design Open-label intervention. Setting Centre for Addiction and Mental Health, Toronto. Participants Subjects with schizophrenia age 50 years or more who were clinically stable and previously maintained on oral risperidone for more than 6 months. Intervention A dose reduction of risperidone of up to 40%, followed by a 3-month follow-up. Measurements Dopamine D2/3 RRO in dorsal putamen was assessed, using the region of interest analysis of [11C]raclopride PET scans, before and after the dose reduction. Clinical assessments included the Positive and Negative Syndrome Scale and the Simpson-Angus Scale. Results Nine subjects (mean ± SD age: 58 ± 7 years; mean ± SD baseline risperidone dose: 3.4 ± 1.6 mg/day) participated in the study. Extrapyramidal symptoms (EPS) were present in six subjects and were associated with 70% or more D2/3 RRO in the putamen (range: 70%-87%). Following the dose reduction, EPS resolved in five subjects. Two subjects experienced a clinical worsening at 52% and at less than 50% D2/3 RRO. Conclusion EPS diminished less than 70% D2/3 RRO, which suggests a lower therapeutic window for older patients with schizophrenia than that for younger patients. Although these findings have to be replicated in a larger sample, they have important implications for future drug development and clinical guidelines in late-life schizophrenia.