論文 - 内田　裕之

Effects of age and age of onset on prescribed antipsychotic dose in schizophrenia spectrum disorders: A survey of 1,418 patients in Japan

Uchida H., Suzuki T., Mamo D., Mulsant B., Tanabe A., Inagaki A., Watanabe K., Yagi G., Tomita M.

American Journal of Geriatric Psychiatry （American Journal of Geriatric Psychiatry）  16 （ 7 ） 584 - 593 2008年07月

ISSN  10647481

　概要を見る

The relationship between age and prescribed antipsychotic dose in patients with schizophrenia has been examined by assuming only a linear correlation in two age subgroups at most. The age of illness onset has also not been under adequate consideration in past prescription surveys. The objective of this study was to better evaluate these age effects on antipsychotic dose prescribed in these patients across a broad age range. Methods: Review of prescriptions for antipsychotic medications in patients with schizophrenia spectrum disorders was conducted across 30 sites in Tokyo. A total of 1,418patients (655 inpatients, 763 males, age range: 16.6-90.2 years) were studied. Results: Age had significant effects on prescribed antipsychotic dose; the dose increased with age through the third decade, subsequently plateaued, and decreased after the fifth decade. The age of illness onset also had significant effects on the dose; late-onset schizophrenia (LOS) and very-late-onset schizophrenia-like psychoses (VLOS) patients received lower doses than early onset schizophrenia (EOS) patients. LOS and VLOS patients who did not experience any hospitalization for the previous year were treated with 1/2 and 1/3, respectively, of the dose for EOS of comparable current age. Conclusion: Our results suggested biphasic effects of age on antipsychotic dose prescribed in patients with schizophrenia spectrum disorders. The natural history of schizophrenia and physiological aging may contribute to this inverted U-shaped relationship. In addition, our results may add another evidence of dis-ttnction among EOS, LOS, and VLOS from a clinical psychopharmacological perspective. © 2008 American Association for Geriatric Psychiatry.

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Adsorption/oxidation of CO on highly dispersed Pt catalyst studied by combined electrochemical and ATR-FTIRAS methods: oxidation of CO adsorbed on carbon-supported Pt catalyst and unsupported Pt black.

Kunimatsu K, Sato T, Uchida H, Watanabe M

Langmuir : the ACS journal of surfaces and colloids 24 （ 7 ） 3590 - 601 2008年04月

ISSN  0743-7463

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Quetiapine extended-release versus immediate-release formulation

Mamo David C., Uchida Hiroyuki, Vitcu Irina, Barsoum Penny, Gendron Alain, Goldstein Jeffrey, Kapur Shitij

Journal of Clinical Psychiatry 69 （ 1 ） 81 - 86 2008年01月

ISSN  0160-6689

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<p>Objective: The pharmacokinetic and pharmacodynamic profile of the immediate-release (IR) formulation of quetiapine is characterized by a rapid peak in plasma level and striatal dopamine D₂ receptor occupancy, followed by a rapid decrease to baseline levels, necessitating the use of twice-daily dosing. An extended-release (XR) formulation of quetiapine is currently being developed to achieve similar efficacy using a once-daily dosing regimen. We compared the central D₂ receptor binding between the IR and XR formulations. Method: In this open-label, crossover positron emission tomography study using [¹¹C]-raclopride, we compared the central D₂ receptor binding potential at expected peak and trough plasma levels using equivalent daily doses of the IR and XR formulations (300, 600, and 800 mg/day) in 12 subjects. Data were collected from April 2002 to May 2003. Results: The mean plasma level of quetiapine at trough was significantly lower than that at peak for all dose groups of both formulations except for IR 300 and 800 mg (all p values &lt; .05), while the mean plasma level did not differ significantly between formulations at trough and peak. The mean occupancy at peak was significantly higher than that at trough for all dose groups other than IR 800 mg/day (all p values &lt; .05) and did not differ significantly between formulations at trough and peak. Conclusion: Once-daily dosing of the XR formulation gives peak and trough plasma levels and central D₂ receptor occupancy comparable to twice-daily dosing of the IR formulation. These data should be considered while determining equivalent doses, as well as switching strategies.</p>

Quetiapine extended-release versus immediate-release formulation: A positron emission tomography study

Mamo D., Uchida H., Vitcu I., Barsoum P., Gendron A., Goldstein J., Kapur S.

Journal of Clinical Psychiatry （Journal of Clinical Psychiatry）  69 （ 1 ） 81 - 86 2008年01月

ISSN  01606689

　概要を見る

Objective: The pharmacokinetic and pharmacodynamic profile of the immediate-release (IR) formulation of quetiapine is characterized by a rapid peak in plasma level and striatal dopamine D2 receptor occupancy, followed by a rapid decrease to baseline levels, necessitating the use of twice-daily dosing. An extended-release (XR) formulation of quetiapine is currently being developed to achieve similar efficacy using a once-daily dosing regimen. We compared the central D2 receptor binding between the IR and XR formulations. Method: In this open-label, crossover positron emission tomography study using [11C]-raclopride, we compared the central D2 receptor binding potential at expected peak and trough plasma levels using equivalent daily doses of the IR and XR formulations (300, 600, and 800 mg/day) in 12 subjects. Data were collected from April 2002 to May 2003. Results: The mean plasma level of quetiapine at trough was significantly lower than that at peak for all dose groups of both formulations except for IR 300 and 800 mg (all p values < .05), while the mean plasma level did not differ significantly between formulations at trough and peak. The mean occupancy at peak was significantly higher than that at trough for all dose groups other than IR 800 mg/day (all p values < .05) and did not differ significantly between formulations at trough and peak. Conclusion: Once-daily dosing of the XR formulation gives peak and trough plasma levels and central D2 receptor occupancy comparable to twice-daily dosing of the IR formulation. These data should be considered while determining equivalent doses, as well as switching strategies. © Copyright 2008 Physicians Postgraduate Press, Inc.

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Glycodelin blocks progression to S phase and inhibits cell growth: a possible progesterone-induced regulator for endometrial epithelial cell growth.

Ohta K, Maruyama T, Uchida H, Ono M, Nagashima T, Arase T, Kajitani T, Oda H, Morita M, Yoshimura Y

Molecular human reproduction 14 （ 1 ） 17 - 22 2008年01月

ISSN  1360-9947

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Treatment target in schizophrenia

Suzuki Takefumi, Uchida Hiroyuki, Watanabe Koichiro, Kashima Haruo

Psychopharmacology Bulletin 41 （ 4 ） 80 - 102 2008年

ISSN  0048-5764

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<p>Patients with schizophrenia have many problems as well as symptoms, and various rating scales have been in use to address them. The authors review past representative rating scales and some pivotal studies to focus on treatment target in schizophrenia. Traditionally, positive symptoms have been the main target of treatment. However, other crucial domains such as negative and cognitive symptoms, and subjective perspectives are drawing due attention because of their clinical relevance. Given many domains to be addressed, there have eventually been too many assessment scales to be selected and widely utilized in real-world clinical settings, and there has been still no concrete consensus on which scales to utilize in a given situation, which is currently decided at the discretion of the investigators. Measurement is frequently difficult even with the existing assessments, especially as what constitutes an acceptable clinical status is hard to define, considering highly hetero generous nature of the illness. Many rating scales are met with limitations especially in time and in pragmatic comprehensiveness, which often hinder their routine application in time-limited busy settings. Still, problems and functioning of patients are the reasonable target to evaluate for measurement-based treatment. The authors suggest assessment of problems resulting from symptoms together with objective functioning, which clinical psychiatrists are actually doing in everyday practice, would serve as a minimum set of standardized assessment in schizophrenia, and the newly developed TIP-Sz and FACT-Sz would serve for that purpose. Other crucial viewpoints could be supplemented with (subjective) assessment scales as appropriate.</p>

陽性症状の神経化学的基盤に関する仮説 – Aberrant Salience仮説を中心に

内田 裕之

Schizophrenia Frontier 8   252-256 2008年

研究論文（学術雑誌）, 単著

Salience仮説とドパミン

内田裕之,渡邊衡一郎,八木剛平

臨床精神薬理 11   1435-1440 2008年

研究論文（学術雑誌）, 共著

A potentially aborted neuroleptic malignant syndrome following seclusion against uncontrollable water intoxication.

Suzuki T., Uchida H., Watanabe K., Kashima H.

Psychopharmacology bulletin （Psychopharmacology bulletin）  41 （ 1 ） 164 - 170 2008年

ISSN  0048-5764

　概要を見る

Water intoxication in schizophrenia poses a great clinical challenge, and occasionally, behavioral restrictions are unavoidable. A patient with refractory schizophrenia comorbid with severe water intoxication had an apparent weight variation of ,7 kg/day to 65 kg. As he fell twice, when he had been treated with antipsychotic megadose therapy, he was secluded with restricted water access of 3 L/day. Two days later, consciousness level deteriorated significantly with autonomic instability; however, he was treated with intravenous hydration plus dantrolene and recovered completely on the following day. The sodium/chloride levels and serum osmolarity, which had been abnormally low, normalized abruptly. Only after seclusion was it found that his dry weight had been only 52 kg. The first description of such a case was indicative of a potentially aborted neuroleptic malignant syndrome. He is now treated with olanzapine, valproate, and lorazepam, with some success. Caution is required for secluding extreme cases of uncontrollable water intoxication.

Treatment target in schizophrenia: a critical review and a clinical suggestion.

Suzuki T., Uchida H., Watanabe K., Kashima H.

Psychopharmacology bulletin （Psychopharmacology bulletin）  41 （ 4 ） 80 - 102 2008年

ISSN  00485764

　概要を見る

Patients with schizophrenia have many problems as well as symptoms, and various rating scales have been in use to address them. The authors review past representative rating scales and some pivotal studies to focus on treatment target in schizophrenia. Traditionally, positive symptoms have been the main target of treatment. However, other crucial domains such as negative and cognitive symptoms, and subjective perspectives are drawing due attention because of their clinical relevance. Given many domains to be addressed, there have eventually been too many assessment scales to be selected and widely utilized in real-world clinical settings, and there has been still no concrete consensus on which scales to utilize in a given situation, which is currently decided at the discretion of the investigators. Measurement is frequently difficult even with the existing assessments, especially as what constitutes an acceptable clinical status is hard to define, considering highly hetero generous nature of the illness. Many rating scales are met with limitations especially in time and in pragmatic comprehensiveness, which often hinder their routine application in time-limited busy settings. Still, problems and functioning of patients are the reasonable target to evaluate for measurement-based treatment. The authors suggest assessment of problems resulting from symptoms together with objective functioning, which clinical psychiatrists are actually doing in everyday practice, would serve as a minimum set of standardized assessment in schizophrenia, and the newly developed TIP-Sz and FACT-Sz would serve for that purpose. Other crucial viewpoints could be supplemented with (subjective) assessment scales as appropriate.

How effective is it to sequentially switch among Olanzapine, Quetiapine and Risperidone? - A randomized, open-label study of algorithm-based antipsychotic treatment to patients with symptomatic schizophrenia in the real-world clinical setting

Suzuki T., Uchida H., Watanabe K., Nomura K., Takeuchi H., Tomita M., Tsunoda K., Nio S., Den R., Manki H., Tanabe A., Yagi G., Kashima H.

Psychopharmacology （Psychopharmacology）  195 （ 2 ） 285 - 295 2007年12月

ISSN  0033-3158

　概要を見る

Rationale: Evidence on sequential trial with atypical antipsychotics has been scarce. Objectives: We conducted an algorithm-based antipsychotic pharmacotherapy. Materials and methods: In this open-label study, patients with schizophrenia (DSM-IV) were treated with antipsychotic monotherapy, step-by-step, with each trial lasting up to 8 weeks. At baseline, they were highly symptomatic to score more than 54 in the total Brief Psychiatric Rating Scale (BPRS1-7) score. When the posttreatment BPRS score was above 70% of the baseline, they were subsequently treated with another and up to three atypicals. Basically, anticholinergics were prohibited, and only adjunctive allowed was lorazepam. The secondary endpoint was a clinical status good enough to be discharged for 66 inpatients and a successful continuation therapy with the same antipsychotic agent for more than 6 months for 12 outpatients. Results: Three groups of 26 patients each were randomized to Olanzapine, Quetiapine, or Risperidone. Thirty-nine (50%) responded to the first agent (Olanzapine16, Quetiapine9, Risperidone14), and 14 responded to the second. Only two showed response to the third, and 16 failed to respond to all three antipsychotics, with only 7 dropouts. Overall, there were 22 Olanzapine, 14 Quetiapine, and 19 Risperidone responders. Based on the secondary outcome, 20 Olanzapine-treated (average maximum dose, 15.4 mg), 10 Quetiapine-treated (418 mg), and 20 Risperidone-treated (4.10 mg) patients responded. The difference in response as the first choice was significant (p<0.05). Relative doses of those failing to respond were comparable (Olanzapine 18.3 mg, Quetiapine 564 mg, Risperidone5.47 mg). Extrapyramidal symptoms did not change significantly. Conclusions: When the first atypical antipsychotic is inadequate, switching to the second is worth trying, although some remain treatment-refractory. Quetiapine may be inferior to Olanzapine and Risperidone in symptomatic patients. © 2007 Springer-Verlag.

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Identification of novel suppressors for Mog1 implies its involvement in RNA metabolism, lipid metabolism and signal transduction.

Oki M, Ma L, Wang Y, Hatanaka A, Miyazato C, Tatebayashi K, Nishitani H, Uchida H, Nishimoto T

Gene 400 （ 1-2 ） 114 - 21 2007年10月

ISSN  0378-1119

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Use of atypical antipsychotic medications in later life

Rajji T., Mulsant B., Uchida H., Mamo D.

Geriatrics and Aging （Geriatrics and Aging）  10 （ 9 ） 578 - 587 2007年10月

ISSN  1488-8408

　概要を見る

Antipsychotics are increasingly being prescribed to older patients for the management of a variety of neuropsychiatric conditions. Available evidence supports the use of second-generation antipsychotics (SGAs) when treating these conditions. However, given their modest clinical effect for certain conditions (e.g., behavioural and psychological symptoms of dementia), their adverse effects, and their safety profile, a careful analysis of their risks and benefits is needed before initiating treatment with an SGA for an older patient. Among SGAs, choice of medication should be guided by their respective clinical indications and adverse effect profile, with use of lower initial and target doses (compared to younger adults) and periodic reviews of whether or not their continued use is warranted.

Minimizing antipsychotic medication obviated the need for enema against severe constipation leading to paralytic ileus

Suzuki T., Uchida H., Watanabe K., Kashima H.

Journal of Clinical Pharmacy and Therapeutics 32 （ 5 ） 525 - 527 2007年10月

ISSN  0269-4727

　概要を見る

<p>Objective: To report the usefulness of antipsychotic dose-reduction for avoiding paralytic ileus in a patient with chronic schizophrenia and comorbid dementia. Case summary: A 65-year-old in-patient developed severe paralytic ileus warranting a transfer to the general hospital. Constipation was very troublesome and he often needed enema to prevent intestinal obstruction. He had originally been treated with 24 mg of bromperidol, which was reduced to 4 mg, and other psychotropic treatments were simultaneously simplified. As a result, bowel habits improved and enema is now only rarely necessary. Constipation is a frequent adverse effect of antipsychotics and adjunctive psychotropics, which can be severe and may lead to life-threatening paralytic ileus. Dose-reduction obviated a necessity of enema against persistent constipation, while the patient's mental status remained under control. Assessment using the Naranjo probability scale revealed a definite causal relationship. Discussion: With an increasing number of elderly patients with schizophrenia, more cases of severe gastrointestinal motility problems from antipsychotic medication are to be expected. In this patient population dose-reduction of antipsychotics and simplification of concomitant psychotropics should be seriously considered.</p>

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Minimizing antipsychotic medication obviated the need for enema against severe constipation leading to paralytic ileus: A case report

Suzuki T., Uchida H., Watanabe K., Kashima H.

Journal of Clinical Pharmacy and Therapeutics （Journal of Clinical Pharmacy and Therapeutics）  32 （ 5 ） 525 - 527 2007年10月

ISSN  02694727

　概要を見る

Objective: To report the usefulness of antipsychotic dose-reduction for avoiding paralytic ileus in a patient with chronic schizophrenia and comorbid dementia. Case summary: A 65-year-old in-patient developed severe paralytic ileus warranting a transfer to the general hospital. Constipation was very troublesome and he often needed enema to prevent intestinal obstruction. He had originally been treated with 24 mg of bromperidol, which was reduced to 4 mg, and other psychotropic treatments were simultaneously simplified. As a result, bowel habits improved and enema is now only rarely necessary. Constipation is a frequent adverse effect of antipsychotics and adjunctive psychotropics, which can be severe and may lead to life-threatening paralytic ileus. Dose-reduction obviated a necessity of enema against persistent constipation, while the patient's mental status remained under control. Assessment using the Naranjo probability scale revealed a definite causal relationship. Discussion: With an increasing number of elderly patients with schizophrenia, more cases of severe gastrointestinal motility problems from antipsychotic medication are to be expected. In this patient population dose-reduction of antipsychotics and simplification of concomitant psychotropics should be seriously considered. © 2007 The Authors.

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Multi-detector-row CT angiography as a preoperative evaluation for spinal arteriovenous fistulae.

Yamaguchi S, Eguchi K, Kiura Y, Takeda M, Nagayama T, Uchida H, Ito Y, Hotta T, Arita K, Kurisu K

Neurosurgical review 30 （ 4 ） 321 - 6; discussion 327 2007年10月

ISSN  0344-5607

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Dietary nitrite inhibits early glomerular injury in streptozotocin-induced diabetic nephropathy in rats.

Ohtake K, Ishiyama Y, Uchida H, Muraki E, Kobayashi J

Nitric oxide : biology and chemistry 17 （ 2 ） 75 - 81 2007年09月

ISSN  1089-8603

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An open-label trial of discontinuing benzodiazepines in patients with chronic schizophrenia [6]

Nakajima Shinichiro, Uchida Hiroyuki, Suzuki Takefumi, Tomita Masayuki, Tsunoda Kenichi, Kitta Masaya, Takeuchi Hiroyoshi, Nomura Kensuke, Watanabe Koichiro, Kashima Haruo

Journal of Clinical Psychopharmacology 27 （ 4 ） 401 - 403 2007年08月

ISSN  0271-0749

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Treating a schizophrenic patient with severe tardive dystonia without antipsychotics

Suzuki Takefumi, Uchida Hiroyuki, Watanabe Koichiro, Kashima Haruo

Progress in Neuro-Psychopharmacology and Biological Psychiatry 31 （ 5 ） 1141 - 1142 2007年06月

ISSN  0278-5846

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Reply to comments by Dr Magalhães [15]

Uchida Hiroyuki, Takeuchi Hiroyoshi, Suzuki Takefumi, Nomura Kensuke, Watanabe Koichiro, Kashima Haruo

Journal of Clinical Psychopharmacology 27 （ 3 ） 318 - 319 2007年06月

ISSN  0271-0749

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