Details of a Researcher - Uchida, Hiroyuki

Papers - Uchida, Hiroyuki

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Increased antipsychotic sensitivity in elderly patients: Evidence and mechanisms

Uchida H., Mamo D., Mulsant B., Pollock B., Kapur S.

Journal of Clinical Psychiatry (Journal of Clinical Psychiatry) 70 ( 3 ) 397 - 405 2009.03

ISSN 01606689

Objective: The primary objective of this article is to review the literature regarding clinical effects, pharmacokinetics, and pharmacodynamics of antipsychotics in older people and to examine potential mechanisms underlying the age-related antipsychotic sensitivity. Data Sources: Data for this review were identified by searches of PubMed (1950-2007) and references from relevant articles and books. Search terms included antipsychotic, neuroleptic, elderly, aging, pharmacokinetics, pharmacodynamics, and dopamine, and only articles written in English or Japanese were consulted. Data Selection: Studies, reviews, and books pertaining to the clinical effects, pharmacokinetics, and pharmacodynamics with regard to the use of antipsychotics in older patients were selected. Data Synthesis: The prevailing practices and clinical guidelines suggest that elderly patients can obtain therapeutic benefits at a lower dose and experience adverse effects from antipsychotics more often than younger patients, although there are still few trials that have directly compared elderly patients with the young. The literature suggests an age-related increase in brain access of drugs and demonstrates a decrease with age in the principal components in the dopaminergic system, including endogenous dopamine level and dopamine receptor density. Conclusions: While clinicians conclusively hold that patients become more sensitive to antipsychotics as they become older, this proposition has only modest empirical support and warrants further investigation. Age-related functional decline in the dopaminergic system predicts lower antipsychotic doses for older patients. We propose a hierarchical series of testable hypotheses to address the relative contribution of age-related pharmacokinetic and pharmacodynamic changes to antipsychotic drug sensitivity. © Copyright 2009 Physicians Postgraduate Press, Inc.

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Sensitivity of older patients to antipsychotic motor side effects: A PET study examining potential mechanisms

Uchida H., Kapur S., Mulsant B.H., Graff-Guerrero A., Pollock B.G., Mamo D.C.

American Journal of Geriatric Psychiatry (American Journal of Geriatric Psychiatry) 17 ( 3 ) 255 - 263 2009.03

ISSN 10647481

OBJECTIVE:: It is generally held that the elderly are more sensitive to motor side effects of antipsychotics, although the mechanisms for such an effect are not fully understood. The objective of this study was to examine whether this sensitivity is due to a central pharmacokinetic (i.e., higher occupancy for a given plasma level) or pharmacodynamic (i.e., greater functional effects for a given occupancy) effect. DESIGN:: Crosssectional. SETTING:: Centre for Addiction and Mental Health, Toronto, Ontario, Canada. PARTICIPANTS:: Thirteen subjects aged 50 (mean ± standard deviation age: 62 ± 9 years) with schizophrenia or schizoaffective disorder who were receiving risperidone. MEASUREMENTS:: Dopamine D2 binding potential in the striatum, using [C]raclopride positron emission tomography scan. D2 receptor occupancy was calculated, using age-corrected measure from healthy individuals and region of interest analysis. RESULTS:: The authors observed the expected nonlinear relationship between total risperidone and 9-hydroxyrisperidone plasma level and striatal D2 receptor occupancy. The estimated plasma level of risperidone plus 9-hydroxyrisperidone associated with 50% maximal receptor occupancy was 7.3 ng/mL, which is similar to what has been reported in younger patients. However, extrapyramidal side effects (EPS) were observed in seven subjects at D2 occupancy of 34%-79%, occupancy levels that are lower than previously reported for younger patients in whom EPS are rare at occupancies lower than 80%. CONCLUSION:: The observation of greater functional effect (EPS in this case) for a given drug occupancy than the younger patients supports a pharmacodynamic mechanism for age-related antipsychotic drug sensitivity. This finding has important implications for dosing of antipsychotics in older patients with schizophrenia. © 2009 American Association for Geriatric Psychiatry.

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Identification and quantification of oxygen species adsorbed on Pt(111) single-crystal and polycrystalline Pt electrodes by photoelectron spectroscopy.

Wakisaka M, Suzuki H, Mitsui S, Uchida H, Watanabe M

Langmuir : the ACS journal of surfaces and colloids 25 ( 4 ) 1897 - 900 2009.02

ISSN 0743-7463

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Antipsychotic-induced paroxysmal perceptual alteration in a patient with bipolar disorder

Nakajima Shinichiro, Suzuki Takefumi, Uchida Hiroyuki, Watanabe Koichiro, Kashima Haruo

Progress in Neuro-Psychopharmacology and Biological Psychiatry 33 ( 1 ) 160 - 161 2009.02

ISSN 0278-5846

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Should adjunctive antipsychotic treatment be continued in remitted patients with depression?

Uchida Hiroyuki, Suzuki Takefumi, Watanabe Koichiro, Kashima Haruo

Psychiatry and Clinical Neurosciences 63 ( 1 ) 126 2009.02

ISSN 1323-1316

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Augmentation of atypical antipsychotics with valproic acid. An open-label study for most difficult patients with schizophrenia

Suzuki Takefumi, Uchida Hiroyuki, Takeuchi Hiroyoshi, Nakajima Shinichiro, Nomura Kensuke, Tanabe Akira, Yagi Gohei, Watanabe Koichiro, Kashima Haruo

Human Psychopharmacology (Human Psychopharmacology) 24 ( 8 ) 628 - 638 2009

ISSN 0885-6222

Objective: Most difficult inpatients with schizophrenia are in serious needs but obviously underrepresented in clinical trials. Methods: Very challenging patients received open-label treatment with atypical antipsychotics concurrently augmented with valproic acid. The primary outcome was the newly developed Functional Assessment for Comprehensive Treatment of Schizophrenia (FACT-Sz). Patients improving more than 20 points were classified as responders. Results: Mean age and illness duration of 28 participants (22male) were 42 y.o. and 20 years, respectively. They had spent a half of their life admitted after the onset. The average Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression-Severity (CGI-S) were very severe at 79 and 6.1, respectively, with the baseline Global Assessment of Functioning (GAF) of as low as 21. As a result of augmentation, there were nine responders, 12 partial responders, and seven non-responders including only two patients who got worse. The main antipsychotics were mostly either risperidone or olanzapine. Mean maximum oral dose and blood level of valproic acid were 1907 mg and 91.7μg/ml, respectively. Overall significant improvements whilst to an inadequate degree were noted in clinical parameters. Valproate augmentation was generally well tolerated but serious adverse effects included thrombocytopenia, anaemia and sedation/falls. Conclusions: While these preliminary results need to be tested against tenacious monotherapy or polypharmacy involving clozapine, augmenting atypical antipsychotics with valproic acid can be useful for very severe schizophrenia.

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統合失調症の維持期における抗精神病薬の最小維持用量：その意義と課題

Uchida Hiroyuki

臨床精神薬理 2009

Research paper (scientific journal), Joint Work

抗精神病薬は単剤化しなければならないのか

Uchida Hiroyuki

精神科 2009

Research paper (scientific journal), Joint Work

Novel rating scales for schizophrenia - Targeted Inventory on Problems in Schizophrenia (TIP-Sz) and Functional Assessment for Comprehensive Treatment of Schizophrenia (FACT-Sz)

Suzuki Takefumi, Uchida Hiroyuki, Nomura Kensuke, Takeuchi Hiroyoshi, Nakajima Shinichiro, Tanabe Akira, Yagi Gohei, Watanabe Koichiro, Kashima Haruo

Schizophrenia Research (Schizophrenia Research) 106 ( 2-3 ) 328 - 336 2008.12

ISSN 0920-9964

Objective: Many rating scales have been in use to evaluate various symptomatic domains, and eventually there are too many scales to be selected and widely utilized in busy real-world settings. Relevant, quick, and user-friendly assessment scales are needed to facilitate measurement-based treatment of schizophrenia. Methods: The authors created unique convenient assessment scales: Targeted Inventory on Problems in Schizophrenia (TIP-Sz), and Functional Assessment for Comprehensive Treatment of Schizophrenia (FACT-Sz). The TIP-Sz consists of 10 items (behavioral dyscontrol/disorganization, hostility/agitation/violence, indifference/affective withdrawal/motor retardation, symptoms on mood/anxiety/obsession/compulsion, insight/reality testing, social competence/independence, adherence to treatment, therapeutic alliance/comfort of therapists on the situation, overall prognostic impression, and subjective well-being/satisfaction with therapy). They are all common and frequently problematic, and each item is rated from 0-10. The FACT-Sz evaluates psychosocial functioning of patients with a score of 0-100, and is judged entirely on an objective basis. Their correlations with the frequently utilized Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF), and Clinical Global Impression-Severity subscale were determined. Results: Data on 36 patients, assessed separately by four experienced psychiatrists, were analyzed. Under an excellent interrater reliability among raters (Intraclass correlation coefficients: 0.822-0.966), correlations among the scales were very high (Spearman's ρ: 0.825-0.909), and other indicators of the scale were generally good. Specifically, the TIP-Sz and FACT-Sz could be rated at 1/3-1/4 of time to complete the PANSS and GAF. Conclusion: The TIP-Sz and FACT-Sz proved to be reliable and valid, which would be of value in daily clinical practice as a minimum standardized assessment set.

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A randomized, open-label comparison of 2 switching strategies to aripiprazole treatment in patients with schizophrenia

Takeuchi Hiroyoshi, Suzuki Takefumi, Uchida Hiroyuki, Nakajima Shinichiro, Nomura Kensuke, Kikuchi Toshiaki, Manki Hiroshi, Watanabe Koichiro, Kashima Haruo

Journal of Clinical Psychopharmacology 28 ( 5 ) 540 - 543 2008.10

ISSN 0271-0749

Although recent treatment guidelines for schizophrenia recommend that the prior antipsychotic agent should remain stable for at least 2 weeks when aripiprazole is introduced, there is no trial-based evidence to support this strategy. This study was designed to compare this strategy with another conventional one in patients with schizophrenia. We conducted a randomized, 14-week, open-label trial to compare the following 2 switching strategies: (1) add-on of aripiprazole on a current regimen, wait for 4 weeks, and the tapering of prior antipsychotics and (2) add-on of aripiprazole and the simultaneous tapering of prior antipsychotics in patients with schizophrenia. Aripiprazole was initiated at 12 mg/d and then titrated between 12 and 30 mg. The previous antipsychotic medication was reduced biweekly by 25%. Assessments included the Clinical Global Impression Scale Schizophrenia version, the Drug-Induced Extrapyramidal Symptoms Scale, and the Subjective Well-being Under Neuroleptics, Short Version, Japanese Edition. Impressions toward their assigned strategy were also subjectively evaluated at baseline and end point. Fifty-three patients were enrolled, and 48 patients completed this trial. No significant differences were found in changes from the baseline in the total Clinical Global Impression Scale Schizophrenia version severity, Drug-Induced Extrapyramidal Symptoms Scale, and Subjective Well-being Under Neuroleptics, Short Version, Japanese Edition scores throughout the study period between the 2 strategies. Both strategies were judged by subjects to be tolerable and favorable without between-group differences. In conclusion, both strategies were found to be objectively safe and well tolerated. Taken together with similar results from subjective assessments, it would be reasonable to choose either of these 2 strategies in clinical practice based on a patients' preference.

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A randomized, open-label comparison of 2 switching strategies to aripiprazole treatment in patients with schizophrenia: Add-on, wait, and tapering of previous antipsychotics versus add-on and simultaneous tapering

Takeuchi H., Suzuki T., Uchida H., Nakajima S., Nomura K., Kikuchi T., Manki H., Watanabe K., Kashima H.

Journal of Clinical Psychopharmacology (Journal of Clinical Psychopharmacology) 28 ( 5 ) 540 - 543 2008.10

ISSN 02710749

Although recent treatment guidelines for schizophrenia recommend that the prior antipsychotic agent should remain stable for at least 2 weeks when aripiprazole is introduced, there is no trial-based evidence to support this strategy. This study was designed to compare this strategy with another conventional one in patients with schizophrenia. We conducted a randomized, 14-week, open-label trial to compare the following 2 switching strategies: (1) add-on of aripiprazole on a current regimen, wait for 4 weeks, and the tapering of prior antipsychotics and (2) add-on of aripiprazole and the simultaneous tapering of prior antipsychotics in patients with schizophrenia. Aripiprazole was initiated at 12 mg/d and then titrated between 12 and 30 mg. The previous antipsychotic medication was reduced biweekly by 25%. Assessments included the Clinical Global Impression Scale Schizophrenia version, the Drug-Induced Extrapyramidal Symptoms Scale, and the Subjective Well-being Under Neuroleptics, Short Version, Japanese Edition. Impressions toward their assigned strategy were also subjectively evaluated at baseline and end point. Fifty-three patients were enrolled, and 48 patients completed this trial. No significant differences were found in changes from the baseline in the total Clinical Global Impression Scale Schizophrenia version severity, Drug-Induced Extrapyramidal Symptoms Scale, and Subjective Well-being Under Neuroleptics, Short Version, Japanese Edition scores throughout the study period between the 2 strategies. Both strategies were judged by subjects to be tolerable and favorable without between-group differences. In conclusion, both strategies were found to be objectively safe and well tolerated. Taken together with similar results from subjective assessments, it would be reasonable to choose either of these 2 strategies in clinical practice based on a patients' preference. Copyright © 2008 by Lippincott Williams & Wilkins.

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Monthly administration of long-acting injectable risperidone and striatal dopamine D₂ receptor occupancy for the management of schizophrenia

Uchida Hiroyuki, Mamo David C., Kapur Shitij, Labelle Alain, Shammi Chekkera, Mannaert Erik J L, Mann Steve W., Remington Gary

Journal of Clinical Psychiatry 69 ( 8 ) 1281 - 1286 2008.08

ISSN 0160-6689

Objective: Long-acting risperidone administered intramuscularly biweekly is approved for the management of schizophrenia. However, dosing of long-acting antipsychotics is frequently extended in clinical practice, and a recent clinical trial has lent support to monthly dosing of long-acting risperidone. The objective of this positron emission tomography (PET) study was to examine the striatal dopamine D₂ binding of long-acting risperidone administered intramuscularly once a month. Method: Following at least 3 maintenance monthly injections of 50 mg long-acting risperidone, 7 patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder underwent PET using [¹¹C]raclopride to measure D₂ binding potential within 4 days of the next scheduled injection. Data were collected from May to October 2003. This PET study was part of a larger 52-week clinical study wherein individuals received long-acting risperidone once monthly over a 1-year interval. One-year follow-up data were obtained from the 52-week parent investigation. Results: The mean ± SD D₂ receptor occupancy was 56% ± 24% (range, 29%-82%). Of note, there were 4 subjects with less than 60% D₂ occupancy, none of whom relapsed over the course of the 1-year follow-up. The mean ± SD total plasma level of risperidone plus 9-hydroxyrisperidone was 16.6 ± 12.3 ng/mL (range, 5.7-40.8). Conclusion: As with plasma levels, there was considerable variability in D₂ occupancy levels for individuals receiving long-acting risperidone. This work suggests a possibility that sustained D₂ occupancy at or above the accepted threshold with acute clinical response may not be necessary to maintain response, a hypothesis with important clinical implications as we consider antipsychotic dosing and future antipsychotic development. Trial Registration: clinicaltrials.gov Identifier: NCT00236353

Effectiveness of antipsychotic polypharmacy for patients with treatment refractory schizophrenia

Suzuki Takefumi, Uchida Hiroyuki, Watanabe Koichiro, Nakajima Shinichiro, Nomura Kensuke, Takeuchi Hiroyoshi, Tanabe Akira, Yagi Gohei, Kashima Haruo

Human Psychopharmacology 23 ( 6 ) 455 - 463 2008.08

ISSN 0885-6222

Objective: To evaluate the effectiveness of antipsychotic polypharmacy in a methodologically sound manner. Methods: In this open-label study, 17 patients with treatment-refractory schizophrenia, who failed to respond to a sequential monotherapy with olanzapine, quetiapine and risperidone, were subsequently treated with a combination therapy with olanzapine plus risperidone for at least 8 weeks. Results: Seven responded according to the primary endpoint defined as the post-treatment Brief Psychiatric Rating Scale being less than 70% of the pretreatment values, and they were classified as such an average of 10 weeks after the initiation of polypharmacy. Two of them were successful in a later conversion to monotherapy. None dropped out prematurely. Four (out of 13 inpatients) got better enough to be discharged from the hospital, while six patients did not show any response. The Global Assessment of Functioning score improved from 37.1 to 53.0 in responders (mean maximum dose: olanzapine 12.9 mg; risperidone 3.14 mg), while it showed non-significant changes among others (mean maximum dose: olanzapine 14.5 mg; risperidone 5.50 mg). Body weight, prolactin, and total cholesterol increased significantly. Conclusions: Antipsychotic polypharmacy might be sometimes helpful for difficult populations but at the cost of adverse effects. More studies of antipsychotic combination therapy versus clozapine, augmentation strategies or tenacious longer-term monotherapy are warranted for refractory schizophrenia.

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Effectiveness of antipsychotic polypharmacy for patients with treatment refractory schizophrenia: An open-label trial of olanzapine plus risperidone for those who failed to respond to a sequential treatment with olanzapine, quetiapine and risperidone

Suzuki T., Uchida H., Watanabe K., Nakajima S., Nomura K., Takeuchi H., Tanabe A., Yagi G., Kashima H.

Human Psychopharmacology (Human Psychopharmacology) 23 ( 6 ) 455 - 463 2008.08

ISSN 08856222

Objective: To evaluate the effectiveness of antipsychotic polypharmacy in a methodologically sound manner. Methods: In this open-label study, 17 patients with treatment-refractory schizophrenia, who failed to respond to a sequential monotherapy with olanzapine, quetiapine and risperidone, were subsequently treated with a combination therapy with olanzapine plus risperidone for at least 8 weeks. Results: Seven responded according to the primary endpoint defined as the post-treatment Brief Psychiatric Rating Scale being less than 70% of the pretreatment values, and they were classified as such an average of 10 weeks after the initiation of polypharmacy. Two of them were successful in a later conversion to monotherapy. None dropped out prematurely. Four (out of 13 inpatients) got better enough to be discharged from the hospital, while six patients did not show any response. The Global Assessment of Functioning score improved from 37.1 to 53.0 in responders (mean maximum dose: olanzapine 12.9 mg; risperidone 3.14 mg), while it showed non-significant changes among others (mean maximum dose: olanzapine 14.5 mg; risperidone 5.50 mg). Body weight, prolactin, and total cholesterol increased significantly. Conclusions: Antipsychotic polypharmacy might be sometimes helpful for difficult populations but at the cost of adverse effects. More studies of antipsychotic combination therapy versus clozapine, augmentation strategies or tenacious longer-term monotherapy are warranted for refractory schizophrenia. Copyright © 2008 John Wiley & Sons, Ltd.

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Monthly administration of long-acting injectable risperidone and striatal dopamine D<inf>2</inf> receptor occupancy for the management of schizophrenia

Uchida H., Mamo D.C., Kapur S., Labelle A., Shammi C., Mannaert E.J.L., Mann S.W., Remington G.

Journal of Clinical Psychiatry (Journal of Clinical Psychiatry) 69 ( 8 ) 1281 - 1286 2008.08

ISSN 01606689

Objective: Long-acting risperidone administered intramuscularly biweekly is approved for the management of schizophrenia. However, dosing of long-acting antipsychotics is frequently extended in clinical practice, and a recent clinical trial has lent support to monthly dosing of long-acting risperidone. The objective of this positron emission tomography (PET) study was to examine the striatal dopamine D2 binding of long-acting risperidone administered intramuscularly once a month. Method: Following at least 3 maintenance monthly injections of 50 mg long-acting risperidone, 7 patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder underwent PET using [11C]raclopride to measure D2 binding potential within 4 days of the next scheduled injection. Data were collected from May to October 2003. This PET study was part of a larger 52-week clinical study wherein individuals received long-acting risperidone once monthly over a 1-year interval. One-year follow-up data were obtained from the 52-week parent investigation. Results: The mean ± SD D2 receptor occupancy was 56% ± 24% (range, 29%-82%). Of note, there were 4 subjects with less than 60% D2 occupancy, none of whom relapsed over the course of the 1-year follow-up. The mean ± SD total plasma level of risperidone plus 9-hydroxyrisperidone was 16.6 ± 12.3 ng/mL (range, 5.7-40.8). Conclusion: As with plasma levels, there was considerable variability in D2 occupancy levels for individuals receiving long-acting risperidone. This work suggests a possibility that sustained D2 occupancy at or above the accepted threshold with acute clinical response may not be necessary to maintain response, a hypothesis with important clinical implications as we consider antipsychotic dosing and future antipsychotic development. Trial Registration: clinicaltrials.gov Identifier: NCT00236353 © Copyright 2008 Physicians Postgraduate Press, Inc.

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Effects of age and age of onset on prescribed antipsychotic dose in schizophrenia spectrum disorders

Uchida Hiroyuki, Suzuki Takefumi, Mamo David C., Mulsant Benoit H., Tanabe Akira, Inagaki Ataru, Watanabe Koichiro, Yagi Gohei, Tomita Masayuki

American Journal of Geriatric Psychiatry 16 ( 7 ) 584 - 593 2008.07

ISSN 1064-7481

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.

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[Age, period and birth-cohort effects on marriage rates in Japanese women between 1985 and 2005, and comparison of trends of effects between marriage and birth rates].

Uchida H, Odagiri Y, Ohtake K, Kobayashi J

[Nihon koshu eisei zasshi] Japanese journal of public health 55 ( 7 ) 440 - 8 2008.07

ISSN 0546-1766

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 2008.07

ISSN 10647481

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 2008.04

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 2008.01

ISSN 0160-6689

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.

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