研究者詳細 - 内田　裕之

論文 - 内田　裕之

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Antipsychotic Polypharmacy and Corrected QT Interval

Takeuchi Hiroyoshi, Suzuki Takefumi, Remington Gary, Uchida Hiroyuki

Canadian Journal of Psychiatry 60 （ 5 ） 215 - 222 2015年05月

ISSN 0706-7437

RESULTS: A total of 21 articles (10 clinical trials, 4 observational studies, and 7 case reports) met inclusion criteria. The clinical trials have shown that a combination treatment with risperidone or pimozide is not obviously related to an increase in QTc interval, whereas ziprasidone or sertindole combined with clozapine may prolong QTc interval. Among the 4 observational studies, antipsychotic polypharmacy was not clearly associated with QTc prolongation in 3 studies, each cross-sectional. In contrast, one prospective study showed a significant increase in QTc interval following antipsychotic coadministration. The case reports indicated an increased risk of QTc prolongation in at least some patients receiving antipsychotic polypharmacy.CONCLUSIONS: Currently available evidence fails to confirm that antipsychotic polypharmacy worsens QTc prolongation in general, although the evidence is scarce and inconsistent. Clinicians are advised to remain conservative in resorting to antipsychotic polypharmacy, as a combination of some QTc-prolongation liable antipsychotics may further prolong QTc interval, and efficacy supporting the clinical benefits of antipsychotic polypharmacy is equivocal, at best.OBJECTIVE: It remains unclear whether antipsychotic polypharmacy, a common clinical practice, is related to an increased risk of corrected time between start of Q wave and end of T wave (QTc) interval prolongation. We conducted a systematic review of the literature to address this important issue.METHOD: A systematic literature search was conducted in October 2014, using MEDLINE, Embase, and PsycINFO. Studies and case reports were included if they reported QTc intervals or QTc interval changes before and after antipsychotic polypharmacy or QTc intervals in both antipsychotic polypharmacy and monotherapy groups.

Cardiac Sudden Death in Psychiatric Patients

Uchida Hiroyuki, Suzuki Takefumi

Canadian Journal of Psychiatry 60 （ 5 ） 203 - 205 2015年05月

ISSN 0706-7437

Challenging the need for sustained blockade of dopamine D<inf>2</inf> receptor estimated from antipsychotic plasma levels in the maintenance treatment of schizophrenia

Tsuboi Takashi, Suzuki Takefumi, Bies Robert R., Remington Gary, Pollock Bruce G., Mimura Masaru, Uchida Hiroyuki

Schizophrenia Research 164 （ 1-3 ） 149 - 154 2015年05月

ISSN 0920-9964

Objective: Blockade of dopamine D<inf>2</inf> receptors with antipsychotics above 65% is associated with optimal chance of clinical response although recent data suggest a lower threshold for the maintenance treatment of schizophrenia. The objective of this study was to prospectively examine whether such continuous high blockade would be necessary for maintenance treatment. Method: In this single-blind, 52-week, randomized controlled trial, clinically stable patients with schizophrenia receiving risperidone or olanzapine were randomly assigned to the continuous D<inf>2</inf> blockade (i.e. an estimated trough D<inf>2</inf> blockade of >65%) or non-continuous blockade group (i.e. an estimated peak level of >65% with an estimated trough level of <65%). Oral doses corresponding to the assigned blockade levels were estimated from random plasma drug concentrations, using the models we developed; antipsychotic doses were then adjusted accordingly. Psychopathology and side effects were assessed at baseline and one year with the Positive and Negative Syndrome Scale (PANSS), Simpson-Angus Scale (SAS), and Abnormal Involuntary Movement Scale (AIMS). Results: Sixty-eight subjects (34 in each group) were enrolled. Twenty-six (76.5%) and thirty-one (91.2%) subjects completed the study in the continuous and non-continuous blockade groups, respectively, without any significant group difference. No significant differences were found on any of the assessment scales between the two groups. The degree of dosage change was small in both groups. Conclusion: These results offer support that the threshold for D<inf>2</inf> receptor blockade in the maintenance treatment can be lower than 65%. However, these preliminary findings have to be confirmed through double-blind, larger scale trials with longer follow-up periods.

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Antipsychotic polypharmacy and corrected QT interval: A systematic review

Takeuchi H., Suzuki T., Remington G., Uchida H.

Canadian Journal of Psychiatry （Canadian Journal of Psychiatry） 60 （ 5 ） 215 - 222 2015年05月

ISSN 07067437

Objective: It remains unclear whether antipsychotic polypharmacy, a common clinical practice, is related to an increased risk of corrected time between start of Q wave and end of T wave (QTc) interval prolongation. We conducted a systematic review of the literature to address this important issue. Method: A systematic literature search was conducted in October 2014, using MEDLINE, Embase, and PsycINFO. Studies and case reports were included if they reported QTc intervals or QTc interval changes before and after antipsychotic polypharmacy or QTc intervals in both antipsychotic polypharmacy and monotherapy groups. Results: A total of 21 articles (10 clinical trials, 4 observational studies, and 7 case reports) met inclusion criteria. The clinical trials have shown that a combination treatment with risperidone or pimozide is not obviously related to an increase in QTc interval, whereas ziprasidone or sertindole combined with clozapine may prolong QTc interval. Among the 4 observational studies, antipsychotic polypharmacy was not clearly associated with QTc prolongation in 3 studies, each cross-sectional. In contrast, one prospective study showed a significant increase in QTc interval following antipsychotic coadministration. The case reports indicated an increased risk of QTc prolongation in at least some patients receiving antipsychotic polypharmacy. Conclusions: Currently available evidence fails to confirm that antipsychotic polypharmacy worsens QTc prolongation in general, although the evidence is scarce and inconsistent. Clinicians are advised to remain conservative in resorting to antipsychotic polypharmacy, as a combination of some QTc-prolongation liable antipsychotics may further prolong QTc interval, and efficacy supporting the clinical benefits of antipsychotic polypharmacy is equivocal, at best.

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Challenging the need for sustained blockade of dopamine D<inf>2</inf> receptor estimated from antipsychotic plasma levels in the maintenance treatment of schizophrenia: A single-blind, randomized, controlled study

Tsuboi T., Suzuki T., Bies R., Remington G., Pollock B., Mimura M., Uchida H.

Schizophrenia Research （Schizophrenia Research） 164 （ 1-3 ） 149 - 154 2015年05月

ISSN 09209964

© 2015 Elsevier B.V. Objective: Blockade of dopamine D2 receptors with antipsychotics above 65% is associated with optimal chance of clinical response although recent data suggest a lower threshold for the maintenance treatment of schizophrenia. The objective of this study was to prospectively examine whether such continuous high blockade would be necessary for maintenance treatment. Method: In this single-blind, 52-week, randomized controlled trial, clinically stable patients with schizophrenia receiving risperidone or olanzapine were randomly assigned to the continuous D2 blockade (i.e. an estimated trough D2 blockade of >65%) or non-continuous blockade group (i.e. an estimated peak level of >65% with an estimated trough level of <65%). Oral doses corresponding to the assigned blockade levels were estimated from random plasma drug concentrations, using the models we developed; antipsychotic doses were then adjusted accordingly. Psychopathology and side effects were assessed at baseline and one year with the Positive and Negative Syndrome Scale (PANSS), Simpson-Angus Scale (SAS), and Abnormal Involuntary Movement Scale (AIMS). Results: Sixty-eight subjects (34 in each group) were enrolled. Twenty-six (76.5%) and thirty-one (91.2%) subjects completed the study in the continuous and non-continuous blockade groups, respectively, without any significant group difference. No significant differences were found on any of the assessment scales between the two groups. The degree of dosage change was small in both groups. Conclusion: These results offer support that the threshold for D2 receptor blockade in the maintenance treatment can be lower than 65%. However, these preliminary findings have to be confirmed through double-blind, larger scale trials with longer follow-up periods.

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Dopamine D<inf>2/3</inf> receptor availability in the striatum of antipsychotic-free older patients with schizophrenia-A [11C]-raclopride PET study

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

Schizophrenia Research （Schizophrenia Research） 164 （ 1-3 ） 263 - 267 2015年05月

ISSN 09209964

© 2015 Elsevier B.V. Background: No study has examined dopamine D2/3 receptor (D2/3R) availability in antipsychotic-free older patients with schizophrenia. Methods: We included patients with schizophrenia 50years or older who were antipsychotic-free for at least 3months. We compared non-displaceable binding potential (BPND) of [11C]-raclopride in the caudate, putamen, ventral striatum, and globus pallidus between patients and age- and sex-matched healthy controls. Results: Ten patients participated (antipsychotic-naive=4). No differences in BPND were found between patients and controls in any ROIs (F(1, 72)=42, p=52). Conclusion: The preliminary results suggest no differences in D2/3R availability between antipsychotic-free older patients with schizophrenia and controls.

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Whether to increase or maintain dosage of mirtazapine in early nonimprovers with depression

Ueno F., Nakajima S., Suzuki T., Abe T., Sato Y., Mimura M., Uchida H.

Journal of Clinical Psychiatry （Journal of Clinical Psychiatry） 76 （ 4 ） 434 - 439 2015年04月

ISSN 0160-6689

© Copyright 2015 Physicians Postgraduate Press, Inc. Objective: To compare outcomes between increasing versus maintaining the dose of mirtazapine in patients with depression without initial improvement. Method: Data from a 6-week double-blind randomized placebo-controlled trial of mirtazapine in major depressive disorder (DSM-IV) conducted from November 2004 to December 2005 were used. Percentages of remitters (ie, a score of ≤ 7 in the 17-item Hamilton Depression Rating Scale [HDRS-17]) and HDRS-17 score changes from baseline to week 6 were compared in the following 2 pairs, using Fisher exact test or mixed-effects model for repeated measures: (1) subjects who failed to show a ≥ 20% decrease in the HDRS-17 total scores at week 1 but were assigned to continue 15 mg/d (stay<inf>15</inf> group) versus those who were assigned to increase the dose to 30 mg/d (increase<inf>30</inf> group) and (2) subjects who failed to show a ≥ 20% decrease in the HDRS-17 total scores with 30 mg/d at week 2 but were assigned to continue 30 mg/d (stay<inf>30</inf> group) versus those who were assigned to increase the dose to 45 mg/d (increase45 group). Results: The increase<inf>30</inf> group showed a numerically but not significantly higher remission rate and a significantly greater decrease in the HDRS-17 total score at week 6 than the stay<inf>15</inf> group (34.7% [8 of 23 patients] vs 14.3% [3 of 21 patients], P = .2; least squares mean, -15.8 vs -10.9, P = .003). No significant differences were found between the increase<inf>45</inf> and stay<inf>30</inf> groups. Conclusions: Dose increase of mirtazapine from 15 mg/d to 30 mg/d may be effective for patients with depression without initial improvement. However, effectiveness may not be the case beyond 30 mg/d.

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Improvement in treatment results of glioblastoma over the last three decades and beneficial factors.

Kawano H, Hirano H, Yonezawa H, Yunoue S, Yatsushiro K, Ogita M, Hiraki Y, Uchida H, Habu M, Fujio S, Oyoshi T, Bakhtiar Y, Sugata S, Yamahata H, Hanaya R, Tokimura H, Arita K

British journal of neurosurgery 29 （ 2 ） 206 - 12 2015年04月

ISSN 0268-8697

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Steroid psychosis caused by perioperative steroid replacement for pituitary adenoma

Mizutani Katsuhiro, Toda Masahiro, Kikuchi Ryogo, Uchida Hiroyuki, Yoshida Kazunari

Keio Journal of Medicine 64 （ 1 ） 11 - 15 2015年03月

ISSN 0022-9717

Steroid psychosis is a frequent complication of steroid treatment. Although perioperative steroid replacement therapy is generally administered in patients undergoing pituitary surgery, there are no previous reports concerning the development of steroid psychosis after perioperative steroid replacement therapy following pituitary surgery. We herein report a case of steroid psychosis induced by perioperative steroid replacement therapy for pituitary surgery. A 35-year-old man presented with a visual disturbance that had persisted for 1 year. A magnetic resonance imaging scan showed a large pituitary tumor, and a laboratory study revealed slight dysfunction of the hypothalamo-pituitary-adrenal axis. The patient was diagnosed with a non-functioning pituitary tumor and underwent tumor resection via the endoscopic endonasal approach. The initial dose of perioperative steroid replacement therapy was 200 mg of hydrocortisone administered immediately before the operation. The replacement dose was gradually tapered and discontinued over a 7-day period. On postoperative day 4, the patient exhibited an elated mood, grandiose delusions, anxiety, and agitation. We diagnosed these psychiatric symptoms as steroid psychosis induced by steroid replacement and we prescribed risperidone as a treatment. The symptoms gradually improved and did not recur. This case highlights the risk of steroid psychosis following treatment with perioperative steroid replacement therapy for pituitary adenoma and raises questions regarding the appropriateness of perioperative steroid replacement for pituitary adenoma.

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Steroid psychosis caused by perioperative steroid replacement for pituitary adenoma: A case report

Mizutani K., Toda M., Kikuchi R., Uchida H., Yoshida K.

Keio Journal of Medicine （Keio Journal of Medicine） 64 （ 1 ） 11 - 15 2015年03月

ISSN 00229717

© 2015 by The Keio Journal of Medicine. Steroid psychosis is a frequent complication of steroid treatment. Although perioperative steroid replacement therapy is generally administered in patients undergoing pituitary surgery, there are no previous reports concerning the development of steroid psychosis after perioperative steroid replacement therapy following pituitary surgery. We herein report a case of steroid psychosis induced by perioperative steroid replacement therapy for pituitary surgery. A 35-year-old man presented with a visual disturbance that had persisted for 1 year. A magnetic resonance imaging scan showed a large pituitary tumor, and a laboratory study revealed slight dysfunction of the hypothalamo-pituitary-adrenal axis. The patient was diagnosed with a non-functioning pituitary tumor and underwent tumor resection via the endoscopic endonasal approach. The initial dose of perioperative steroid replacement therapy was 200 mg of hydrocortisone administered immediately before the operation. The replacement dose was gradually tapered and discontinued over a 7-day period. On postoperative day 4, the patient exhibited an elated mood, grandiose delusions, anxiety, and agitation. We diagnosed these psychiatric symptoms as steroid psychosis induced by steroid replacement and we prescribed risperidone as a treatment. The symptoms gradually improved and did not recur. This case highlights the risk of steroid psychosis following treatment with perioperative steroid replacement therapy for pituitary adenoma and raises questions regarding the appropriateness of perioperative steroid replacement for pituitary adenoma.

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

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

Schizophrenia Research 162 （ 1-3 ） 296 2015年03月

ISSN 0920-9964

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Dependence on benzodiazepines in patients with panic disorder

Fujii Kazuhito, Uchida Hiroyuki, Suzuki Takefumi, Mimura Masaru

Psychiatry and Clinical Neurosciences 69 （ 2 ） 93 - 99 2015年02月

ISSN 1323-1316

Aims The aim of this cross-sectional study was to examine the prevalence of psychological dependence on benzodiazepines in outpatients with panic disorder and elucidate demographic and clinical characteristics associated with this condition. Methods Subjects were eligible if they were outpatients in four clinics in Tokyo, Japan, aged 18 years or older and met the diagnostic criteria for panic disorder according to the ICD-10. The subjects received the following assessments: the Severity of Dependence Scale, Japanese Version (SDS), the Self-Report Version of Panic Disorder Severity Scale, Japanese Version (PDSS-SR), and the Quick Inventory of Depressive Symptomatology-Self Report, Japanese Version. The following information was also collected: age, sex, ethnicity, duration of illness, physical and psychiatric comorbidities, and details of prescribed psychotropic medications. Results The data from 51 outpatients showed that 31 patients (60.8%) showed psychological dependence (i.e. a total score of ≥5 in the SDS). The proportion of patients with dependence was significantly lower in remitted patients (i.e. a total score of ≤4 in the PDSS) (44.1%, n-=-15/34) than those who were not (94.1%, n-=-16/17) (Pearson χ²-=-11.9, P-<-0.001). A multiple regression analysis showed that the PDSS scores showed a positive correlation with the SDS total scores (β-=-0.60, 95% confidence interval-=-0.30-0.90, P-=-0.0001). Conclusion These findings emphasize the need for enhanced awareness about benzodiazepine dependence in patients and psychiatrists, as well as especially close attention to patients with panic disorder who present severe symptomatology.

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Dependence on benzodiazepines in patients with panic disorder: A cross-sectional study

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

Psychiatry and Clinical Neurosciences （Psychiatry and Clinical Neurosciences） 69 （ 2 ） 93 - 99 2015年02月

ISSN 13231316

© 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology. Aims The aim of this cross-sectional study was to examine the prevalence of psychological dependence on benzodiazepines in outpatients with panic disorder and elucidate demographic and clinical characteristics associated with this condition. Methods Subjects were eligible if they were outpatients in four clinics in Tokyo, Japan, aged 18 years or older and met the diagnostic criteria for panic disorder according to the ICD-10. The subjects received the following assessments: the Severity of Dependence Scale, Japanese Version (SDS), the Self-Report Version of Panic Disorder Severity Scale, Japanese Version (PDSS-SR), and the Quick Inventory of Depressive Symptomatology-Self Report, Japanese Version. The following information was also collected: age, sex, ethnicity, duration of illness, physical and psychiatric comorbidities, and details of prescribed psychotropic medications. Results The data from 51 outpatients showed that 31 patients (60.8%) showed psychological dependence (i.e. a total score of ≥5 in the SDS). The proportion of patients with dependence was significantly lower in remitted patients (i.e. a total score of ≤4 in the PDSS) (44.1%, n-=-15/34) than those who were not (94.1%, n-=-16/17) (Pearson χ2-=-11.9, P-<-0.001). A multiple regression analysis showed that the PDSS scores showed a positive correlation with the SDS total scores (β-=-0.60, 95% confidence interval-=-0.30-0.90, P-=-0.0001). Conclusion These findings emphasize the need for enhanced awareness about benzodiazepine dependence in patients and psychiatrists, as well as especially close attention to patients with panic disorder who present severe symptomatology.

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Dietary nitrite supplementation improves insulin resistance in type 2 diabetic KKA(y) mice.

Ohtake K, Nakano G, Ehara N, Sonoda K, Ito J, Uchida H, Kobayashi J

Nitric oxide : biology and chemistry 44 31 - 8 2015年01月

ISSN 1089-8603

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A Proposal for Natural Resilience Theory in Psychopharmacotherapy

Yagi Gohei, Suzuki Takefumi, Uchida Hiroyuki

Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica 117 （ 1 ） 10 - 17 2015年01月

ISSN 0033-2658

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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