Nobumi Miyake

St. Marianna University School of Medicine, Kawasaki Si, Kanagawa, Japan

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Publications (18)73.52 Total impact

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    ABSTRACT: AimsThe purpose of this study was to evaluate the long-term effectiveness and safety of blonanserin, a second-generation antipsychotic drug developed in Japan, in patients with first-episode schizophrenia. Methods Twenty-three antipsychotic-naive patients with first-episode schizophrenia were treated within an open-label, 1-year, prospective trial of blonanserin (2-24mg/day). Clinical evaluations were conducted at baseline and 2, 6, and 12 months after the start of treatment. The main outcome measures were changes in subjective well-being and subjective quality of life, as assessed by the Subjective Well-being under Neuroleptic treatment scale Short form-Japanese version and the Schizophrenia Quality of Life Scale-Japanese version, respectively. Secondary outcome measures included the Positive and Negative Syndrome Scale, the Brief Assessment of Cognition in Schizophrenia-Japanese version, laboratory tests, bodyweight, and extrapyramidal symptoms. ResultsFourteen patients (60.9%) remained on the study at 1 year. In the intention-to-treat analysis, significant improvements were observed in several subscales on the Subjective Well-being under Neuroleptic treatment scale Short form-Japanese version, the Schizophrenia Quality of Life Scale-Japanese version, and the Brief Assessment of Cognition in Schizophrenia-Japanese version, and in all factor scores on the Positive and Negative Syndrome Scale. Improvement in depressive symptoms with blonanserin treatment was positively correlated with improvements in subjective well-being and subjective quality of life, as well as verbal memory. No significant changes were noted for any safety measure during the 1-year study period. Conclusions Blonanserin was well tolerated and effective for the treatment of first-episode schizophrenia in terms of subjective wellness, cognition, and a wide range of pathological symptoms. Further large-scale studies are warranted to confirm our findings.
    Psychiatry and Clinical Neurosciences 05/2014; 68(12). DOI:10.1111/pcn.12202 · 1.62 Impact Factor
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    Shin Ogino · Seiya Miyamoto · Nobumi Miyake · Noboru Yamaguchi
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    ABSTRACT: All currently available antipsychotic drugs are the dopamine D2 receptor antagonists and are capable of producing extrapyramidal side-effects (EPS). Anticholinergic drugs are primarily used to treat EPS or prevent EPS induced by antipsychotics in the treatment of psychosis and schizophrenia. However, they can cause a variety of distressing peripheral side-effects (e.g. dry mouth, urinary disturbances, and constipation) and central adverse effects (e.g. cognitive impairment, worsening of tardive dyskinesia, and delirium). Disturbances in cognitive abilities are cardinal features of schizophrenia from its earliest phases and account for much of the functional disability associated with the illness. It is likely that long-term concomitant administration of anticholinergics exacerbates the underlying cognitive impairment in patients with schizophrenia and subsequently affects patients' quality of life. Thus, current treatment guidelines for schizophrenia generally do not recommend the prophylactic and long-term use of anticholinergics. However, the high use of long-term anticholinergic drugs with antipsychotics has been identified as an important issue in the treatment of schizophrenia in several countries. To assess the benefits and limits of anticholinergic use in psychosis and schizophrenia, this article will provide a brief review of the pharmacology and clinical profiles of anticholinergic drugs and will focus on their effects on cognitive function in schizophrenia, particularly during the course of the early phase of the illness. In addition, we will address the effects of discontinuation of anticholinergics on cognitive function in patients with schizophrenia and provide a strategy for adjunctive anticholinergic use in patients treated with long-acting injectable antipsychotics.
    Psychiatry and Clinical Neurosciences 09/2013; 68(1). DOI:10.1111/pcn.12088 · 1.62 Impact Factor
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    ABSTRACT: Blonanserin was developed as an antipsychotic drug in Japan and approved for the treatment of schizophrenia. It belongs to a series of 4-phenyl-2-(1-piperazinyl)pyridines and acts as an antagonist at dopamine D2, D3, and serotonin 5-HT2A receptors. Blonanserin has low affinity for 5-HT2C, adrenergic α1, histamine H1, and muscarinic M1 receptors, but displays relatively high affinity for 5-HT6 receptors. In several short-term double-blind clinical trials, blonanserin had equal efficacy as haloperidol and risperidone for positive symptoms in patients with chronic schizophrenia and was also superior to haloperidol for improving negative symptoms. Blonanserin is generally well tolerated and has a low propensity to cause metabolic side effects and prolactin elevation. We recently reported that blonanserin can improve some types of cognitive function associated with prefrontal cortical function in patients with first-episode and chronic schizophrenia. Taken together, these results suggest that blonanserin may be a promising candidate for a first-line antipsychotic for acute and maintenance therapy for schizophrenia. Further comparative studies are warranted to clarify the benefit/risk profile of blonanserin and its role in the treatment of schizophrenia.
    Neuropsychiatric Disease and Treatment 04/2013; 9:587-94. DOI:10.2147/NDT.S34433 · 2.15 Impact Factor
  • Nobumi Miyake · Seiya Miyamoto · L. Fredrik Jarskog
    Clinical Schizophrenia & Related Psychoses 10/2012; 6(3):122-133. DOI:10.3371/CSRP.6.3.4
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    ABSTRACT: Since the introduction of chlorpromazine and throughout the development of the new-generation antipsychotic drugs (APDs) beginning with clozapine, the D(2) receptor has been the target for the development of APDs. Pharmacologic actions to reduce neurotransmission through the D(2) receptor have been the only proven therapeutic mechanism for psychoses. A number of novel non-D(2) mechanisms of action of APDs have been explored over the past 40 years but none has definitively been proven effective. At the same time, the effectiveness of treatments and range of outcomes for patients are far from satisfactory. The relative success of antipsychotics in treating positive symptoms is limited by the fact that a substantial number of patients are refractory to current medications and by their lack of efficacy for negative and cognitive symptoms, which often determine the level of functional impairment. In addition, while the newer antipsychotics produce fewer motor side effects, safety and tolerability concerns about weight gain and endocrinopathies have emerged. Consequently, there is an urgent need for more effective and better-tolerated antipsychotic agents, and to identify new molecular targets and develop mechanistically novel compounds that can address the various symptom dimensions of schizophrenia. In recent years, a variety of new experimental pharmacological approaches have emerged, including compounds acting on targets other than the dopamine D(2) receptor. However, there is still an ongoing debate as to whether drugs selective for singe molecular targets (that is, 'magic bullets') or drugs selectively non-selective for several molecular targets (that is, 'magic shotguns', 'multifunctional drugs' or 'intramolecular polypharmacy') will lead to more effective new medications for schizophrenia. In this context, current and future drug development strategies can be seen to fall into three categories: (1) refinement of precedented mechanisms of action to provide drugs of comparable or superior efficacy and side-effect profiles to existing APDs; (2) development of novel (and presumably non-D(2)) mechanism APDs; (3) development of compounds to be used as adjuncts to APDs to augment efficacy by targeting specific symptom dimensions of schizophrenia and particularly those not responsive to traditional APD treatment. In addition, efforts are being made to determine if the products of susceptibility genes in schizophrenia, identified by genetic linkage and association studies, may be viable targets for drug development. Finally, a focus on early detection and early intervention aimed at halting or reversing progressive pathophysiological processes in schizophrenia has gained great influence. This has encouraged future drug development and therapeutic strategies that are neuroprotective. This article provides an update and critical review of the pharmacology and clinical profiles of current APDs and drugs acting on novel targets with potential to be therapeutic agents in the future.Molecular Psychiatry advance online publication, 15 May 2012; doi:10.1038/mp.2012.47.
    Molecular Psychiatry 05/2012; 17(12). DOI:10.1038/mp.2012.47 · 15.15 Impact Factor
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    ABSTRACT: The purpose of this study was to evaluate the effects of blonanserin, a novel antipsychotic, on cognitive function in first-episode schizophrenia. Twenty-four antipsychotic-naïve patients with first-episode schizophrenia participated in the study. Blonanserin was given in an open-label design for 8 weeks. The Brief Assessment of Cognition in Schizophrenia-Japanese language version (BACS-J) was administered as the primary outcome measure at baseline and 8 weeks. Clinical evaluation included the Positive and Negative Syndrome Scale (PANSS), the Schizophrenia Quality of Life Scale-Japanese language version (SQLS-J), and the Clinical Global Impression-Severity of Illness Scale (CGI-S). To exclude the possibility of retest effects on the BACS-J, 10 age-matched patients with chronic schizophrenia treated with blonanserin were tested at baseline and after an 8-week interval. Twenty first-episode patients completed the study. Repeated measures analysis of covariance revealed a significant group-by-time interaction effect on the letter fluency task due to better performance in the first-episode group, but not in the control group. Main effect of time or group-by-time interaction effect on the Tower of London task was not significant; however, the first-episode group, but not the control group, showed substantial improvement with a moderate effect size. All items on the PANSS, SQLS-J, and CGI-S significantly improved after 8 weeks of treatment. These results suggest that blonanserin improves some types of cognitive function associated with prefrontal cortical function.
    Human Psychopharmacology Clinical and Experimental 01/2012; 27(1):90-100. DOI:10.1002/hup.1276 · 1.85 Impact Factor
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    ABSTRACT: The high use of long-term benzodiazepines (BZDs) with second-generation antipsychotics (SGAs) has been identified as an important issue in the treatment of schizophrenia in Japan. The aim of this study was to evaluate the effects of gradual reduction or discontinuation of daytime BZD use on cognitive function and quality of life (QOL) in patients with chronic schizophrenia receiving an SGA. Thirty schizophrenic patients who had received an SGA with concomitant BZDs for at least 3 months were enrolled. Before and 4 weeks after tapering of daytime BZDs, the Brief Assessment of Cognition in Schizophrenia Japanese-language version (BACS-J) and the Schizophrenia Quality of Life Scale Japanese-language version (SQLS-J) were administered. Clinical evaluation also included the Positive and Negative Syndrome Scale (PANSS). To compare for practice effects on the BACS-J, 10 patients with chronic schizophrenia were assessed without tapering BZDs. BZDs were reduced or discontinued safely in most patients, and no emergent withdrawal symptoms were observed. Significant improvements were shown in verbal memory, working memory, and composite score, as measured by the BACS-J without practice effects. In addition, the motivation/energy score on the SQLS-J, the negative symptoms and total scores on the PANSS significantly improved after tapering BZDs. Reduction or discontinuation of long-term daytime use of BZDs may be warranted in patients with schizophrenia treated with SGAs, as it may improve cognitive function, subjective QOL, and psychiatric symptoms with no significant adverse effects.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 11/2011; 36(2):300-6. DOI:10.1016/j.pnpbp.2011.11.008 · 4.03 Impact Factor
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    ABSTRACT: Measuring the in vivo occupancy of antipsychotic drugs at dopamine D(2) and D(3) receptors separately has been difficult because of the lack of selective radiotracers. The recently developed [(11)C]-(+)-PHNO is D(3)-preferring, allowing estimates of the relative D(2) and D(3) binding of antipsychotic drugs. We used positron emission tomography (PET) imaging in baboons with [(11)C]-(+)-PHNO to examine the binding of clozapine and haloperidol to D(2) and D(3) receptors. Four animals were scanned with dynamically acquired PET and arterial plasma input functions. Test and retest scans were acquired in single scanning sessions for three subjects to assess the reproducibility of [(11)C]-(+)-PHNO scans. Four additional scans were acquired in each of three subjects following single doses of antipsychotic drugs (clozapine 0.5534 mg/kg, haloperidol 0.0109 mg/kg, two administrations per drug per subject) and compared with baseline scans. The percent change in binding (ΔBP(ND)) following challenges with antipsychotic drugs was measured. A regression model, based on published values of regional D(2) and D(3) fractions of [(11)C]-(+)-PHNO BP(ND) in six brain regions, was used to infer occupancy at D(2) and D(3) receptors. BP(ND) following antipsychotic challenge decreased in all regions. Estimated D(2) : D(3) selectivity was 2.38 for haloperidol and 5.25 for clozapine, similar to published in vitro values for haloperidol (3.03), but slightly higher for clozapine (2.82). These data suggest that acute doses of clozapine and haloperidol bind to D(3) receptors in vivo, and that the lack of D(3) occupancy by antipsychotics observed in some recent imaging studies may be because of other phenomena.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 03/2011; 36(4):887-95. DOI:10.1038/npp.2010.228 · 7.83 Impact Factor
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    ABSTRACT: An imaging method to probe glutamate levels in vivo would allow the study of glutamate transmission in disease states and in response to therapeutic interventions. Here we demonstrate the feasibility of this approach for the first time using positron emission tomography and [(11)C] ABP688, a radiotracer for an allosteric site on the metabotropic glutamate receptor 5. We conducted two sets of experiments in anesthetized baboons: test and retest without pharmacologic challenge and in combination with N-acetylcysteine (NAC), a promoter of the cystine-glutamate antiporter that increases extrasynaptic glutamate release. The goal was to assess whether NAC-induced changes in [(11)C] ABP688 binding potential, ΔBP(ND), could be detected above the noise in the measurement. Linear mixed modeling comparing ΔBP(ND) from test-retest to ΔBP(ND) from NAC challenge across all brain regions showed a highly significant effect of treatment [F(1,40) = 21.2, p < .001]. ΔBP(ND) was significantly different from zero following NAC [F(1,20) = 76.6, p < .001] but not after test-retest studies. NAC induced decrease in [(11)C] ABP688 ΔBP(ND) may be the result of allosteric modulation, although other mechanisms may be at play. We outline steps needed to replicate and validate this method as a new tool to measure in vivo glutamate transmission.
    Biological psychiatry 02/2011; 69(9):822-4. DOI:10.1016/j.biopsych.2010.12.023 · 9.47 Impact Factor
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    ABSTRACT: The high use of long-term antiparkinsonian anticholinergic drugs with antipsychotics has been identified as an important issue in the treatment of schizophrenia in Japan. The aim of this study was to evaluate the effects of gradual discontinuation of biperiden, an anticholinergic drug, on cognitive function and quality of life (QOL) in schizophrenia. Thirty-four schizophrenic patients who had received a second-generation antipsychotic (SGA) with concomitant biperiden for at least 3 months were enrolled. Before and 4 weeks after discontinuation of biperiden, the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS-J) and the Schizophrenia Quality of Life Scale (SQLS-J) were administered. Clinical evaluation also included the Positive and Negative Syndrome Scale (PANSS). To compare the practice effect on BACS-J, 10 chronic patients with schizophrenia were assessed without tapering biperiden. Biperiden was discontinued safely in most patients, and no emergent extrapyramidal symptoms were observed. Significant improvements were shown in attention, processing speed, and composite score, as measured by the BACS-J without practice effect. In addition, the psychosocial condition score on the SQLS-J and the general psychopathology score on the PANSS significantly improved after biperiden discontinuation. Discontinuation of long-term biperiden use may be warranted in patients with schizophrenia treated with SGAs, as it may improve cognitive function, subjective QOL, and psychiatric symptoms with no significant adverse effects.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 01/2011; 35(1):78-83. DOI:10.1016/j.pnpbp.2010.08.030 · 4.03 Impact Factor
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    ABSTRACT: Presynaptic dopamine (DA) transmission has been measured in schizophrenia using different paradigms aimed at providing estimates of the integrity or the activity of the presynaptic dopaminergic neuron. RESEARCHERS HAVE MEASURED: (1) DA synthesis capacity with [(18) F]DOPA, a measure of the activity of dopa decarboxylase, (2) DA release with studies measuring the impact of a DA releasing stimulant challenge on the binding of a D(2) receptor radiotracer, (3) D(2) baseline occupancy by DA, a measure of baseline intrasynaptic DA, assessed by the changes in binding of D(2) radiotracer induced by DA depletion, and (4) the DA and the vesicular monoamine transporters, to assess the integrity of presynaptic terminals. The relationship between DA release and D(2) receptor occupancy at baseline by DA has also been assessed in the same patients. Overall, these different imaging modalities have converged to show a dysregulation of presynaptic dopaminergic activity in schizophrenia, leading to excessive DA release in the striatum, particularly in the projection to the associative striatum, an area of integration between cognitive and limbic cortical inputs. Excessive striatal presynaptic DA is linked to the emergence of acute psychotic symptoms and to their response to treatment in schizophrenia. Understanding the etiology of this dysregulation and its consequences on the rest of the circuitry is important for future drug development.
    CNS Neuroscience & Therapeutics 12/2010; 17(2):104-9. DOI:10.1111/j.1755-5949.2010.00230.x · 3.78 Impact Factor
  • NeuroImage 08/2010; 52. DOI:10.1016/j.neuroimage.2010.04.072 · 6.36 Impact Factor
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    Psychiatry and Clinical Neurosciences 07/2008; 62(3):369. DOI:10.1111/j.1440-1819.2008.01812.x · 1.62 Impact Factor
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    Psychiatry and Clinical Neurosciences 01/2008; 61(6):702-3. DOI:10.1111/j.1440-1819.2007.01739.x · 1.62 Impact Factor
  • International Clinical Psychopharmacology 07/2006; 21(4). DOI:10.1097/00004850-200607000-00081 · 3.10 Impact Factor
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    ABSTRACT: An abstract is unavailable. This article is available as HTML full text and PDF.
    International Clinical Psychopharmacology 04/2005; 20(3):A1. DOI:10.1097/00004850-200505000-00014 · 3.10 Impact Factor
  • International Clinical Psychopharmacology 05/2004; 19(3):181. DOI:10.1097/00004850-200405000-00030 · 3.10 Impact Factor
  • International Clinical Psychopharmacology 05/2004; 19(3):182-183. DOI:10.1097/00004850-200405000-00034 · 3.10 Impact Factor

Publication Stats

196 Citations
73.52 Total Impact Points

Institutions

  • 2005–2014
    • St. Marianna University School of Medicine
      • Department of Neuropsychiatry
      Kawasaki Si, Kanagawa, Japan
  • 2010–2011
    • Columbia University
      • Department of Psychiatry
      New York, New York, United States
    • New York State Psychiatric Institute
      • Anxiety Disorders Clinic
      New York, New York, United States