Details of a Researcher - Uchida, Hiroyuki

Papers - Uchida, Hiroyuki

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Selective serotonin reuptake inhibitor-induced spermatorrhea in 2 patients

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

Journal of Clinical Psychiatry 70 ( 8 ) 1192 - 1193 2009.08

ISSN 0160-6689

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Predictors of clinical worsening after a switch to aripiprazole in patients with schizophrenia

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

Journal of Clinical Psychopharmacology 29 ( 4 ) 394 - 396 2009.08

ISSN 0271-0749

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Proteomic approach for identification of protein S-nitrosation in mouse gastric mucosa treated with S-nitrosoglutathione.

Ohtake K, Shimada N, Uchida H, Kobayashi J

Journal of proteomics 72 ( 5 ) 750 - 60 2009.07

ISSN 1874-3919

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Test-retest variability of high resolution positron emission tomography (PET) imaging of cortical serotonin (5HT_2A) receptors in older, healthy adults

Chow Tiffany W., Mamo David C., Uchida Hiroyuki, Graff-Guerrero Ariel, Houle Sylvain, Smith Gwenn S., Pollock Bruce G., Mulsant Benoit H.

BMC Medical Imaging 9 2009.07

Background: Position emission tomography (PET) imaging using [¹⁸F]-setoperone to quantify cortical 5-HT_2A receptors has the potential to inform pharmacological treatments for geriatric depression and dementia. Prior reports indicate a significant normal aging effect on serotonin 5HT_2A receptor (5HT_2AR) binding potential. The purpose of this study was to assess the test-retest variability of [¹⁸F]-setoperone PET with a high resolution scanner (HRRT) for measuring 5HT_2AR availability in subjects greater than 60 years old. Methods: Six healthy subjects (age range = 65-78 years) completed two [¹⁸F]-setoperone PET scans on two separate occasions 5-16 weeks apart. Results: The average difference in the binding potential (BP_ND) as measured on the two occasions in the frontal and temporal cortical regions ranged between 2 and 12%, with the lowest intraclass correlation coefficient in anterior cingulate regions. Conclusion: We conclude that the test-retest variability of [¹⁸F]-setoperone PET in elderly subjects is comparable to that of [¹⁸F]-setoperone and other 5HT_2AR radiotracers in younger subject samples.

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Test-retest variability of high resolution positron emission tomography (PET) imaging of cortical serotonin (5HT<inf>2A</inf>) receptors in older, healthy adults

Chow T., Mamo D., Uchida H., Graff-Guerrero A., Houle S., Smith G., Pollock B., Mulsant B.

BMC Medical Imaging (BMC Medical Imaging) 9 12 2009.07

Background: Position emission tomography (PET) imaging using [18F]-setoperone to quantify cortical 5-HT2A receptors has the potential to inform pharmacological treatments for geriatric depression and dementia. Prior reports indicate a significant normal aging effect on serotonin 5HT2A receptor (5HT2AR) binding potential. The purpose of this study was to assess the test-retest variability of [18F]-setoperone PET with a high resolution scanner (HRRT) for measuring 5HT2AR availability in subjects greater than 60 years old. Methods: Six healthy subjects (age range = 65-78 years) completed two [18F]-setoperone PET scans on two separate occasions 5-16 weeks apart. Results: The average difference in the binding potential (BPND) as measured on the two occasions in the frontal and temporal cortical regions ranged between 2 and 12%, with the lowest intraclass correlation coefficient in anterior cingulate regions. Conclusion: We conclude that the test-retest variability of [18F]-setoperone PET in elderly subjects is comparable to that of [18F]-setoperone and other 5HT2AR radiotracers in younger subject samples. © 2009 Chow et al; licensee BioMed Central Ltd.

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Persistence and compliance to antidepressant treatment in patients with depression

Sawada Norifusa, Uchida Hiroyuki, Suzuki Takefumi, Watanabe Koichiro, Kikuchi Toshiaki, Handa Takashi, Kashima Haruo

BMC Psychiatry 9 2009.06

Background: Adherence has recently been suggested to be divided into these two components: persistence (i.e., whether patients continue treatment or not) and compliance (i.e., whether patients take doses as instructed). However, no study has yet assessed these two clinically relevant components at the same time in adherence to antidepressant treatment in the clinical outpatient setting. Methods: In this retrospective chart-review, 6-month adherence to antidepressants was examined in 367 outpatients with a major depressive disorder (ICD-10) (170 males; mean ± SD age 37.6 ± 13.9 years), who started antidepressant treatment from April 2006 through March 2007. Additionally, we evaluated Medication Possession Rate (MPR), defined as the total days a medication was dispensed to patients divided by the treatment period. Results: Only 161 patients (44.3%) continued antidepressant treatment for 6 months. Among 252 patients who discontinued their initial antidepressant, 63.1% of these patients did so without consulting their physicians. Sertraline use was associated with a higher persistence rate at month 6 (odds ratio 2.59 in comparison with sulpiride), and the use of anxiolytic benzodiazepines had a positive effect on persistence to antidepressant treatment only at month 1 (odds ratio 2.14). An overall MPR was 0.77; 55.6% of patients were considered compliant (i.e., a MPR of ≥ 0.8). Conclusion: Given a high rate of antidepressant discontinuation without consulting their physicians, closer communication between patients and their physicians should be encouraged. Although the use of anxiolytic benzodiazepines was associated with a higher persistence to antidepressant treatment at month 1, the use of these drugs should be avoided as a rule, given their well-known serious adverse effects.

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Persistence and compliance to antidepressant treatment in patients with depression: A chart review

Sawada N., Uchida H., Suzuki T., Watanabe K., Kikuchi T., Handa T., Kashima H.

BMC Psychiatry (BMC Psychiatry) 9 38 2009.06

Background: Adherence has recently been suggested to be divided into these two components: persistence (i.e., whether patients continue treatment or not) and compliance (i.e., whether patients take doses as instructed). However, no study has yet assessed these two clinically relevant components at the same time in adherence to antidepressant treatment in the clinical outpatient setting. Methods: In this retrospective chart-review, 6-month adherence to antidepressants was examined in 367 outpatients with a major depressive disorder (ICD-10) (170 males; mean ± SD age 37.6 ± 13.9 years), who started antidepressant treatment from April 2006 through March 2007. Additionally, we evaluated Medication Possession Rate (MPR), defined as the total days a medication was dispensed to patients divided by the treatment period. Results: Only 161 patients (44.3%) continued antidepressant treatment for 6 months. Among 252 patients who discontinued their initial antidepressant, 63.1% of these patients did so without consulting their physicians. Sertraline use was associated with a higher persistence rate at month 6 (odds ratio 2.59 in comparison with sulpiride), and the use of anxiolytic benzodiazepines had a positive effect on persistence to antidepressant treatment only at month 1 (odds ratio 2.14). An overall MPR was 0.77; 55.6% of patients were considered compliant (i.e., a MPR of ≥ 0.8). Conclusion: Given a high rate of antidepressant discontinuation without consulting their physicians, closer communication between patients and their physicians should be encouraged. Although the use of anxiolytic benzodiazepines was associated with a higher persistence to antidepressant treatment at month 1, the use of these drugs should be avoided as a rule, given their well-known serious adverse effects. © 2009 Sawada et al; licensee BioMed Central Ltd.

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Strict use of terminology

Uchida Hiroyuki, Suzuki Takefumi

Psychiatry and Clinical Neurosciences 63 ( 3 ) 430 - 431 2009.06

ISSN 1323-1316

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Clozapine exposure and the impact of smoking and gender

Ng Wenzie, Uchida Hiroyuki, Ismail Zahinoor, Mamo David C., Rajji Tarek K., Remington Gary, Sproule Beth, Pollock Bruce G., Mulsant Benoit H., Bies Robert R.

Therapeutic Drug Monitoring 31 ( 3 ) 360 - 366 2009.06

ISSN 0163-4356

The primary objective of this study was to evaluate the magnitude and variability of concentration exposure to clozapine and norclozapine in a real-world clinical setting, with a focus on smoking status, using population pharmacokinetic methodologies. A retrospective review of plasma clozapine and norclozapine concentrations taken from inpatients at the Centre for Addiction and Mental Health, Toronto, from 2001 to 2007 was conducted. A nonlinear mixed-effects model was developed using NONMEM, including age, gender, weight, smoking status, and dosage formulation as covariates. Pharmacokinetic parameters and interindividual and residual variabilities were estimated with 1- and 2-compartment models. A total of 519 plasma clozapine concentrations from 197 patients (138 males; mean ± SD age, 38 ± 13 years; schizophrenia spectrum disorder 98.2%) were included for the analysis. A 1-compartment model with first-order absorption and elimination best described the data. Apparent volume of distribution was fixed to a previously reported value in the literature of 7 L/kg.The population-predicted oral clearance of clozapine and norclozapine was 18.0 and 39.0 L/h, respectively; both the predicted clearance values vary nearly 6-fold (range, 9.18-59.06 and 16.29-97.84 L/h, respectively). For clozapine, smokers and males showed increased oral clearance by 6.0 and 4.5 L/h, respectively. For norclozapine, smokers and male gender were associated with an increased oral clearance of 11.3 and 7.6 L/h, respectively. The formulation of clozapine administered had an impact on the absorption rate with a Ka of 0.14/h for tablet and 10.3/h for the suspension form.The data suggest that smoking and male gender are associated with lower exposure to clozapine and norclozapine due to the higher oral clearance. These findings may account for some of the variability in clozapine exposure and have important implications for individualized drug dosing and therapeutic drug monitoring.

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Clozapine exposure and the impact of smoking and gender: A population pharmacokinetic study

Ng W., Uchida H., Ismail Z., Mamo D.C., Rajji T.K., Remington G., Sproule B., Pollock B.G., Mulsant B.H., Bies R.R.

Therapeutic Drug Monitoring (Therapeutic Drug Monitoring) 31 ( 3 ) 360 - 366 2009.06

ISSN 01634356

The primary objective of this study was to evaluate the magnitude and variability of concentration exposure to clozapine and norclozapine in a real-world clinical setting, with a focus on smoking status, using population pharmacokinetic methodologies. A retrospective review of plasma clozapine and norclozapine concentrations taken from inpatients at the Centre for Addiction and Mental Health, Toronto, from 2001 to 2007 was conducted. A nonlinear mixed-effects model was developed using NONMEM, including age, gender, weight, smoking status, and dosage formulation as covariates. Pharmacokinetic parameters and interindividual and residual variabilities were estimated with 1- and 2-compartment models. A total of 519 plasma clozapine concentrations from 197 patients (138 males; mean ± SD age, 38 ± 13 years; schizophrenia spectrum disorder 98.2%) were included for the analysis. A 1-compartment model with first-order absorption and elimination best described the data. Apparent volume of distribution was fixed to a previously reported value in the literature of 7 L/kg.The population-predicted oral clearance of clozapine and norclozapine was 18.0 and 39.0 L/h, respectively; both the predicted clearance values vary nearly 6-fold (range, 9.18-59.06 and 16.29-97.84 L/h, respectively). For clozapine, smokers and males showed increased oral clearance by 6.0 and 4.5 L/h, respectively. For norclozapine, smokers and male gender were associated with an increased oral clearance of 11.3 and 7.6 L/h, respectively. The formulation of clozapine administered had an impact on the absorption rate with a Ka of 0.14/h for tablet and 10.3/h for the suspension form.The data suggest that smoking and male gender are associated with lower exposure to clozapine and norclozapine due to the higher oral clearance. These findings may account for some of the variability in clozapine exposure and have important implications for individualized drug dosing and therapeutic drug monitoring. Copyright © 2009 by Lippincott Williams & Wilkins.

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Benzodiazepine and antidepressant use in elderly patients with anxiety disorders

Uchida Hiroyuki, Suzuki Takefumi, Mamo David C., Mulsant Benoit H., Kikuchi Toshiaki, Takeuchi Hiroyoshi, Tomita Masayuki, Watanabe Koichiro, Yagi Gohei, Kashima Haruo

Journal of Anxiety Disorders 23 ( 4 ) 477 - 481 2009.05

ISSN 0887-6185

Since the literature on benzodiazepine use in elderly patients with anxiety disorders is limited, a large cross-sectional review of psychotropic prescriptions in 796 patients with neurotic disorders (ICD-10) (age range = 11-91 years) was conducted across 30 sites in Japan. Use of benzodiazepine-derivative anxiolytics was approximately 70% in all decades without a group difference. The proportion of subjects who received prescriptions for benzodiazepine-derivative anxiolytics in the absence of antidepressants was higher in older age groups (e.g., 27.7% and 43.2% in the third and sixth decades, respectively). On the other hand, antidepressants were less frequently prescribed in older age groups (e.g., 59.8% and 41.5% in the third and sixth decades, respectively). The very high use of anxiolytics in the elderly, especially in the absence of concomitant antidepressant use, is a cause for concern since they are not a preferred long-term treatment strategy given their adverse effects in the elderly.

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Benzodiazepine and antidepressant use in elderly patients with anxiety disorders: A survey of 796 outpatients in Japan

Uchida H., Suzuki T., Mamo D., Mulsant B., Kikuchi T., Takeuchi H., Tomita M., Watanabe K., Yagi G., Kashima H.

Journal of Anxiety Disorders (Journal of Anxiety Disorders) 23 ( 4 ) 477 - 481 2009.05

ISSN 08876185

Since the literature on benzodiazepine use in elderly patients with anxiety disorders is limited, a large cross-sectional review of psychotropic prescriptions in 796 patients with neurotic disorders (ICD-10) (age range = 11-91 years) was conducted across 30 sites in Japan. Use of benzodiazepine-derivative anxiolytics was approximately 70% in all decades without a group difference. The proportion of subjects who received prescriptions for benzodiazepine-derivative anxiolytics in the absence of antidepressants was higher in older age groups (e.g., 27.7% and 43.2% in the third and sixth decades, respectively). On the other hand, antidepressants were less frequently prescribed in older age groups (e.g., 59.8% and 41.5% in the third and sixth decades, respectively). The very high use of anxiolytics in the elderly, especially in the absence of concomitant antidepressant use, is a cause for concern since they are not a preferred long-term treatment strategy given their adverse effects in the elderly. © 2008 Elsevier Ltd. All rights reserved.

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Survey of benzodiazepine and antidepressant use in outpatients with mood disorders in Japan

Uchida Hiroyuki, Suzuki Takefumi, Mamo David C., Mulsant Benoit H., Tsunoda Kenichi, Takeuchi Hiroyoshi, Kikuchi Toshiaki, Nakajima Shinichiro, Nomura Kensuke, Tomita Masayuki, Watanabe Koichiro, Kashima Haruo

Psychiatry and Clinical Neurosciences (Psychiatry and Clinical Neurosciences) 63 ( 2 ) 244 - 246 2009.04

ISSN 1323-1316

Data on benzodiazepine use in mood disorders are still limited, especially among seniors. A cross-sectional review of psychotropic prescriptions in 948 outpatients with mood disorders (405 male; mean ± SD age, 52 ± 17 years; age range, 16- 91 years) was conducted in Japan. The use of benzodiazepine-derivative anxiolytics was approximately 60% in all decades, including older patients, without a group difference. The frequent use of benzodiazepines is a cause for concern because they are not preferred treatment, given their well-known adverse effects especially in the elderly.

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Long-term stability of measuring D₂ receptors in schizophrenia patients treated with antipsychotics

Uchida Hiroyuki, Graff-Guerrero Ariel, Mulsant Benoit H., Pollock Bruce G., Mamo David C.

Schizophrenia Research 109 ( 1-3 ) 130 - 133 2009.04

ISSN 0920-9964

Background: While antipsychotic-free schizophrenia patients showed a high degree of within-subject variability in dopamine D₂ receptor density over 6-24 months, no study has examined the long-term stability of D₂ receptor measures in medicated patients. Methods: Four schizophrenia patients receiving a stable dose of risperidone underwent [¹¹C]raclopride positron emission tomography scans on two occasions 5-14 months apart. Results: Plasma risperidone levels were found to be consistent between scans, and consistencies of nondisplaceable D₂ binding potential and D₂ occupancy were good. Conclusions: The finding supports the validity of quantification of D₂ receptor binding in longitudinal PET studies of medicated patients with schizophrenia.

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Long-term stability of measuring D<inf>2</inf> receptors in schizophrenia patients treated with antipsychotics

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

Schizophrenia Research (Schizophrenia Research) 109 ( 1-3 ) 130 - 133 2009.04

ISSN 09209964

Background: While antipsychotic-free schizophrenia patients showed a high degree of within-subject variability in dopamine D2 receptor density over 6-24 months, no study has examined the long-term stability of D2 receptor measures in medicated patients. Methods: Four schizophrenia patients receiving a stable dose of risperidone underwent [11C]raclopride positron emission tomography scans on two occasions 5-14 months apart. Results: Plasma risperidone levels were found to be consistent between scans, and consistencies of nondisplaceable D2 binding potential and D2 occupancy were good. Conclusions: The finding supports the validity of quantification of D2 receptor binding in longitudinal PET studies of medicated patients with schizophrenia. © 2008 Elsevier B.V. All rights reserved.

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Temperature-dependence of hydrogen oxidation reaction rates and CO-tolerance at carbon-supported Pt, Pt-Co, and Pt-Ru catalysts.

Uchida H, Izumi K, Aoki K, Watanabe M

Physical chemistry chemical physics : PCCP 11 ( 11 ) 1771 - 9 2009.03

ISSN 1463-9076

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Sensitivity of older patients to antipsychotic motor side effects

Uchida Hiroyuki, Kapur Shitij, Mulsant Benoit H., Graff-Guerrero Ariel, Pollock Bruce G., Mamo David C.

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

ISSN 1064-7481

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.

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Increased antipsychotic sensitivity in elderly patients

Uchida Hiroyuki, Mamo David C., Mulsant Benoit H., Pollock Bruce G., Kapur Shitij

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

ISSN 0160-6689

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.

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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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