45 results on '"Tsuneyama N"'
Search Results
2. Association between the GIPR gene and the insulin level after glucose loading in schizophrenia patients treated with olanzapine
- Author
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Ono, S, Suzuki, Y, Fukui, N, Sugai, T, Watanabe, J, Tsuneyama, N, and Someya, T
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- 2012
- Full Text
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3. Exploring functional polymorphisms in the dopamine receptor D2 gene using prolactin concentration in healthy subjects
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Fukui, N, Suzuki, Y, Sugai, T, Watanabe, J, Ono, S, Tsuneyama, N, and Someya, T
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- 2011
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4. The differences of incretin concentration after oral glucose tolerance test in patients with schizophrenia
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Ono, S., primary, Suzuki, Y., additional, Fukui, N., additional, Sugai, T., additional, Watanabe, J., additional, Tsuneyama, N., additional, Saito, M., additional, Tajiri, M., additional, and Someya, T., additional
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- 2016
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5. Association between glucose-dependent insulinotropic polypeptide receptor gene and lipid profiles in schizophrenia patients treated with antipsychotics
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Fukui, N., primary, Suzuki, Y., additional, Ono, S., additional, Sugai, T., additional, Watanabe, J., additional, Tsuneyama, N., additional, Saito, M., additional, Tajiri, M., additional, and Someya, T., additional
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- 2016
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6. P.3.f.014 - The differences of incretin concentration after oral glucose tolerance test in patients with schizophrenia
- Author
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Ono, S., Suzuki, Y., Fukui, N., Sugai, T., Watanabe, J., Tsuneyama, N., Saito, M., Tajiri, M., and Someya, T.
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- 2016
- Full Text
- View/download PDF
7. P.3.d.024 - Association between glucose-dependent insulinotropic polypeptide receptor gene and lipid profiles in schizophrenia patients treated with antipsychotics
- Author
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Fukui, N., Suzuki, Y., Ono, S., Sugai, T., Watanabe, J., Tsuneyama, N., Saito, M., Tajiri, M., and Someya, T.
- Published
- 2016
- Full Text
- View/download PDF
8. Association between the GIPR gene and the insulin level after glucose loading in schizophrenia patients treated with olanzapine
- Author
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Ono, S, primary, Suzuki, Y, additional, Fukui, N, additional, Sugai, T, additional, Watanabe, J, additional, Tsuneyama, N, additional, and Someya, T, additional
- Published
- 2011
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- View/download PDF
9. Exploring functional polymorphisms in the dopamine receptor D2 gene using prolactin concentration in healthy subjects
- Author
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Fukui, N, primary, Suzuki, Y, additional, Sugai, T, additional, Watanabe, J, additional, Ono, S, additional, Tsuneyama, N, additional, and Someya, T, additional
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- 2010
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10. Association between insulin resistance and serum insulin-like growth factor 1 levels in patients with non-remitting major depressive disorder.
- Author
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Arinami H, Suzuki Y, Watanabe Y, Tajiri M, Tsuneyama N, and Someya T
- Subjects
- Humans, Blood Glucose metabolism, Cross-Sectional Studies, Diabetes Mellitus, Insulin, Depressive Disorder, Major blood, Depressive Disorder, Major metabolism, Insulin Resistance, Insulin-Like Growth Factor I analysis, Insulin-Like Growth Factor I metabolism
- Abstract
Background: Major depressive disorder (MDD) is linked to an increased risk of diabetes; however, the underlying pathomechanism remains unknown. Although insulin-like growth factor 1 (IGF-1) is involved in the pathogenesis of both insulin resistance (IR) and MDD, no studies have investigated the relationship between IGF-1 and IR in patients with MDD., Methods: We recruited 120 patients with MDD (84 non-remitting patients and 36 remitting patients) and 99 control participants. Blood samples were collected after overnight fasting to investigate associations between serum and clinical factors, such as serum IGF-1 levels and homeostasis model assessment-insulin resistance (HOMA-IR)., Results: Serum IGF-1 levels were higher in patients with non-remitting MDD than in control participants and patients with remitting MDD (P = 0.001 and P = 0.007, respectively). There were no significant differences in HOMA-IR between the three groups. HOMA-IR was positively correlated with serum IGF-1 levels in patients with non-remitting MDD (R = 0.355; P= 0.001) but not in control participants or patients with remitting MDD. A stepwise multiple regression analysis with various clinical factors revealed a positive association of serum IGF-1 levels and body mass index with HOMA-IR in patients with non-remitting MDD., Limitations: This is a cross-sectional study and therefore we cannot draw firm conclusions about causal associations., Conclusions: Serum IGF-1 levels may play a role in IR in patients with MDD who fail to achieve remission. Further studies, including longitudinal studies, are needed to determine the relationship between high serum IGF-1 levels and subsequent IR and diabetes risk., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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11. Serum cortisol and insulin-like growth factor 1 levels in major depressive disorder and schizophrenia.
- Author
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Arinami H, Watanabe Y, Suzuki Y, Tajiri M, Tsuneyama N, and Someya T
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- Humans, Hydrocortisone, Insulin-Like Growth Factor I metabolism, Fasting, Depressive Disorder, Major, Schizophrenia
- Abstract
The pathophysiology underlying major depressive disorder (MDD) and schizophrenia is related to endocrine system functions and includes changes in the blood levels of cortisol and insulin-like growth factor 1 (IGF-1). However, these hormones have not been investigated simultaneously in patients with MDD and schizophrenia. We investigated the differences in serum cortisol and IGF-1 levels among patients with MDD and schizophrenia and controls. We included 129 patients with MDD, 71 patients with schizophrenia, and 71 healthy volunteers. Blood tests were performed between 6:00 am and 11:00 am after fasting. Serum cortisol levels were significantly higher in patients with schizophrenia than in patients with MDD and controls. Serum cortisol levels were significantly higher in patients with MDD than in controls. Serum IGF-1 levels were higher in both patient groups than in controls, whereas there was no significant difference between patients with MDD and schizophrenia. Both cortisol and IGF-1 levels were positively correlated with the Hamilton Rating Scale for Depression score in patients with MDD, whereas cortisol level was positively correlated and IGF-1 level was negatively correlated with the Brief Psychiatric Rating Scale score in patients with schizophrenia. The differences in the level of these hormones suggest pathophysiological differences between these disorders., (© 2023. The Author(s).)
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- 2023
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12. Role of insulin-like growth factor 1, sex and corticosteroid hormones in male major depressive disorder.
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Arinami H, Suzuki Y, Tajiri M, Tsuneyama N, and Someya T
- Subjects
- Dehydroepiandrosterone Sulfate, Humans, Hydrocortisone, Insulin-Like Growth Factor I, Male, Testosterone, Depressive Disorder, Major
- Abstract
Background: Hormones of the hypothalamic-pituitary-gonadal (HPG), hypothalamic-pituitary-adrenal (HPA), and hypothalamic-pituitary-somatotropic (HPS) axes are potentially involved in major depressive disorder (MDD), but these hormones have not been simultaneously investigated in male patients with MDD. We investigated the association between male MDD symptoms and estradiol, testosterone, cortisol, dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor 1 (IGF1)., Methods: Serum estradiol, testosterone, cortisol, DHEAS, and IGF1 levels were measured in 54 male patients with MDD and 37 male controls and were compared with clinical factors. We investigated the associations between hormone levels and Hamilton Depression Rating Scale (HAM-D) scores. The correlations among hormones were also investigated., Results: Patients had significantly lower estradiol levels than controls (22.4 ± 8.4 pg/mL vs. 26.1 ± 8.5 pg/mL, P = 0.040). Serum estradiol levels were negatively correlated with HAM-D scores (P = 0.000094) and positively correlated with Global Assessment of Functioning scores (P = 0.000299). IGF1 levels and the cortisol:DHEAS ratio were higher in patients than in controls (IGF1: 171.5 ± 61.8 ng/mL vs. 144.1 ± 39.2 ng/mL, P = 0.011; cortisol:DHEAS ratio: 0.07 ± 0.05 vs. 0.04 ± 0.02, P = 0.001). DHEAS levels were lower in patients than in controls (227.9 ± 108.4 μg/dL vs. 307.4 ± 131.2 μg/dL, P = 0.002). IGF1, cortisol:DHEAS ratio, and DHEAS were not significantly correlated with HAM-D scores. Cortisol and testosterone levels were not significantly different between patients and controls. Serum estradiol levels were positively correlated with DHEAS levels (P = 0.00062) in patients, but were not significantly correlated with DHEAS levels in controls., Conclusion: Estradiol may affect the pathogenesis and severity of patients with MDD in men, and other hormones, such as those in the HPA and HPS axes, may also be involved in male MDD. Additionally, a correlation between estradiol and DHEAS may affect the pathology of MDD in men.
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- 2021
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13. Hormonal Dynamics Effect of Serum Insulin-Like Growth Factor I and Cortisol/Dehydroepiandrosterone Sulfate Ratio on Symptom Severity of Major Depressive Disorder.
- Author
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Tajiri M, Suzuki Y, Tsuneyama N, Arinami H, and Someya T
- Subjects
- Adult, Female, Humans, Hypothalamo-Hypophyseal System physiopathology, Hypothalamus physiopathology, Male, Middle Aged, Pituitary-Adrenal System physiopathology, Dehydroepiandrosterone Sulfate blood, Depressive Disorder, Major blood, Depressive Disorder, Major physiopathology, Hydrocortisone blood, Insulin-Like Growth Factor I analysis
- Abstract
Background: Insulin-like growth factor I (IGF-I) is a neurotrophic factor produced by the hypothalamic-pituitary-somatotropic axis and is considered a potential contributor to the pathology of major depressive disorder (MDD). Although it is known that the hypothalamic-pituitary-adrenal axis and cortisol are involved in the pathology of MDD, the association with dehydroepiandrosterone sulfate (DHEAS) remains unclear. The current study sought to clarify the relationship between these hormones and the pathology of MDD., Methods: Subjects were 91 Japanese patients with a diagnosis of MDD. Serum IGF-I, cortisol, and DHEAS were measured. Samples were taken before breakfast after overnight fasting. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HAM-D)., Results: Subjects included 59 men and 32 women with an average age of 44.1 ± 13.1 years (mean ± SD). The blood IGF-I level was 152.0 ± 50.0 ng/mL, the cortisol level was 10.1 ± 4.6, and the DHEAS level was 201.3 ± 112.7 μg/dL. The mean HAM-D score was 13.9 ± 9.0. Serum IGF-I levels were not correlated with cortisol. Higher IGF-I, cortisol, and cortisol/DHEAS ratios were associated with higher HAM-D scores (adjusted R = 0.240, P < 0.001), and higher IGF-I and cortisol were associated with higher melancholic or suicide subscores (adjusted R = 0.200, P < 0.001; adjusted R = 0.273, P < 0.001)., Conclusions: Our findings suggest that hormonal dysregulation of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-somatotropic axes may be related to the symptom severity of MDD, melancholia, and suicide-related factors.
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- 2019
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14. Effects of olanzapine on resting heart rate in Japanese patients with schizophrenia.
- Author
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Tajiri M, Suzuki Y, Sugai T, Tsuneyama N, and Someya T
- Subjects
- Adolescent, Adult, Antipsychotic Agents therapeutic use, Dose-Response Relationship, Drug, Female, Humans, Japan, Male, Middle Aged, Olanzapine therapeutic use, Schizophrenia physiopathology, Young Adult, Antipsychotic Agents adverse effects, Heart Rate drug effects, Olanzapine adverse effects, Rest physiology, Schizophrenia drug therapy
- Abstract
It has long been known that antipsychotic drugs (ATP) causes tachycardia, however details such as the differences between ATP are not well known. In recent years, the relationship between the rise in resting heart rate (RHR) and the increased risk of death in the general population has been garnering attention. In this study, we examined the difference in action on RHR between olanzapine (OLZ) and aripiprazole (ARP). The changes in the RHR on switching from OLZ to ARP and on increasing from the starting OLZ dose to the final one were evaluated in 19 outpatients (Study 1) and in 29 outpatients with schizophrenia (Study 2), respectively. To analyze the RHR, electrocardiographic measurements were obtained. At the same day, the Brief Psychiatric Rating Scale (BPRS) was evaluated, and fasting blood samples were drawn after an overnight fast of at least 8 h to examine electrolytes. Both Study 1 and 2 were conducted with the approval of the Gene Ethics Committee of Niigata University Graduate School of Medical and Dental Sciences, and the patients were treated at the outpatient psychiatric clinic at Niigata University Medical and Dental Hospital. All patients had been diagnosed with schizophrenia based on the DSM-IV-TR. In the Study 1, OLZ of 14.6 ± 9.2mg (mean ± standard deviation) was switched to ARP of 20.8 ± 8.1mg. Significant decreases were observed in the mean RHR after the switch to ARP (73.7 ± 9.7 vs 65.8 ± 10.9 beats/min, p = 0.008). In the Study 2, the starting OLZ dose was 7.2 ± 3.2mg and the increasing OLZ dose was 18.3 ± 7.4mg. Significant increases were observed in the mean RHR after increasing OLZ (69.7 ± 14.0 vs 75.6 ± 14.3 beats/min, p = 0.004). In this study, it was shown that OLZ has a stronger RHR enhancing effect compared to ARP and its effects are dose-dependent. If the increase in RHR increases the mortality rate of patients with schizophrenia, it may be necessary to further investigate the differences between ATP in terms of the effect on RHR of second-generation antipsychotics with a strong anticholinergic action or phenothiazine antipsychotics., Competing Interests: The authors have declared that no competing interests exist.
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- 2018
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15. Effect of GWAS-Identified Genetic Variants on Maximum QT Interval in Patients With Schizophrenia Receiving Antipsychotic Agents: A 24-Hour Holter ECG Study.
- Author
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Watanabe J, Fukui N, Suzuki Y, Sugai T, Ono S, Tsuneyama N, Saito M, Tajiri M, and Someya T
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- Adult, Antipsychotic Agents pharmacology, Electrocardiography, Ambulatory trends, Female, Genetic Variation drug effects, Heart Rate drug effects, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide genetics, Schizophrenia drug therapy, Time Factors, Antipsychotic Agents therapeutic use, Electrocardiography, Ambulatory drug effects, Genetic Variation genetics, Genome-Wide Association Study methods, Heart Rate genetics, Schizophrenia genetics
- Abstract
Background: Users of antipsychotics (APs) have a risk of sudden cardiac death (SCD). Sudden cardiac death in such patients is thought to be largely due to drug-induced QT prolongation. It has been reported that many subjects with drug-induced torsades de pointes (TdP) have risk alleles associated with subclinical congenital long QT syndrome., Methods: We investigated the effects of the risk alleles associated with long QT on the QT interval in patients receiving APs using 24-hour Holter electrocardiograms to take into account the circadian fluctuation of QT intervals. We investigated 8 single-nucleotide polymorphisms identified on a GWAS., Results: We found that increased numbers of risk alleles at rs7188697 in NDRG4 and rs11970286 in PLN were the major predictors of an increased maximum QT interval over 24 hours in users of APs., Conclusions: It could be useful to perform a DNA-based analysis before the initiation of APs to reduce the risk of drug-induced torsades de pointes and SCD.
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- 2017
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16. Effect of Serum Leptin on Weight Gain Induced by Olanzapine in Female Patients with Schizophrenia.
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Tsuneyama N, Suzuki Y, Sawamura K, Sugai T, Fukui N, Watanabe J, Ono S, Saito M, and Someya T
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- Adiponectin blood, Adolescent, Adult, Antipsychotic Agents adverse effects, Benzodiazepines adverse effects, Body Mass Index, Female, Humans, Male, Olanzapine, Schizophrenia blood, Tumor Necrosis Factor-alpha blood, Young Adult, Antipsychotic Agents therapeutic use, Benzodiazepines therapeutic use, Leptin blood, Schizophrenia drug therapy, Weight Gain drug effects
- Abstract
Background: Olanzapine (OLZ) treatment is associated with a high risk of weight gain, and may cause abnormalities in glycolipid metabolism. Therefore, the underlying mechanism of OLZ-related weight gain is needed to clarify but not yet been adequately determined. In recent years, adipocytokines such as leptin, adiponectin, and tumor necrosis factor (TNF)-α, which play important roles in energy homeostasis, have been suggested as biomarkers of weight gain. Here, we determined if baseline plasma concentrations of leptin, adiponectin, and TNF-α predict weight gain following OLZ treatment., Methods: We recruited 31 schizophrenia outpatients (12 men and 19 women, 28.8 ± 10.2 years old) that were unmedicated or on another antipsychotic monotherapy medication. Baseline body mass index (BMI) and plasma levels of leptin, adiponectin, and TNF-α were obtained. All patients started or were switched to OLZ monotherapy for a maximum of 1 year. BMI was also obtained at the endpoint., Results: Mean BMI change following OLZ treatment was 2.1 ± 2.7 kg/m2. BMI change from baseline to endpoint negatively-correlated with baseline leptin levels in female patients (r = -0.514, P = 0.024), but not male patients. Baseline adiponectin or TNF-α levels were not correlated with BMI change., Conclusion: Baseline plasma leptin can have an effect on subsequent weight gain following OLZ treatment in female patients with schizophrenia.
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- 2016
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17. Improvement of dumping syndrome and oversecretion of glucose-dependent insulinotropic polypeptide following a switch from olanzapine to quetiapine in a patient with schizophrenia.
- Author
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Watanabe A, Fukui N, Suzuki Y, Motegi T, Igeta H, Tsuneyama N, and Someya T
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- Drug Substitution, Female, Humans, Middle Aged, Olanzapine, Schizophrenia complications, Stomach Neoplasms complications, Antipsychotic Agents therapeutic use, Benzodiazepines therapeutic use, Dumping Syndrome etiology, Gastrectomy adverse effects, Gastric Inhibitory Polypeptide metabolism, Quetiapine Fumarate therapeutic use, Schizophrenia drug therapy, Stomach Neoplasms surgery
- Abstract
Among the most important adverse effects of antipsychotics is abnormal glucose metabolism, which includes not only hyperglycemia but hyperinsulinemia and hypoglycemia. We have previously described five patients who experienced hypoglycemia during treatment with antipsychotics. Thus, an anamnesis of gastric surgery, which often causes dumping syndrome, and treatment with antipsychotics may synergistically induce hypoglycemia. We describe here a patient with schizophrenia under treatment of olanzapine and an anamnesis of gastric surgery, who experienced late dumping syndrome, hyperinsulinemia and overactivation of glucose-dependent insulinotropic polypeptide. Dumping syndrome, however, was improved after the patient was switched from olanzapine to quetiapine., (Copyright © 2015 Elsevier Inc. All rights reserved.)
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- 2015
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18. GIPR Gene Polymorphism and Weight Gain in Patients With Schizophrenia Treated With Olanzapine.
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Ono S, Suzuki Y, Fukui N, Sawamura K, Sugai T, Watanabe J, Tsuneyama N, and Someya T
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- Adolescent, Adult, Aged, Body Mass Index, Body Weight drug effects, Female, Genotype, Humans, Male, Middle Aged, Olanzapine, Young Adult, Antipsychotic Agents therapeutic use, Benzodiazepines therapeutic use, Body Weight genetics, Pharmacogenetics, Polymorphism, Single Nucleotide genetics, Receptors, Gastrointestinal Hormone genetics, Schizophrenia drug therapy, Schizophrenia genetics, Schizophrenia physiopathology
- Abstract
Association between gastric inhibitory polypeptide receptor polymorphism, rs10423928, and body mass index in olanzapine-treated schizophrenia was examined. Body mass index change for the A/T+A/A genotypes was significantly higher than that for the T/T genotype. rs10423928 may predict weight gain in schizophrenia.
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- 2015
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19. Promoter variation in the catechol-O-methyltransferase gene is associated with remission of symptoms during fluvoxamine treatment for major depression.
- Author
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Fukui N, Suzuki Y, Sugai T, Watanabe J, Ono S, Tsuneyama N, and Someya T
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- Female, Humans, Male, Middle Aged, Treatment Outcome, Antidepressive Agents, Second-Generation administration & dosage, Catechol O-Methyltransferase genetics, Depressive Disorder, Major drug therapy, Depressive Disorder, Major enzymology, Fluvoxamine administration & dosage, Promoter Regions, Genetic
- Abstract
We investigated the association between remission of depressive symptoms in fluvoxamine treatment and catechol-O-methyltransferase (COMT) gene. Sixteen SNPs in the COMT gene were investigated in 123 outpatients with major depression. Three single nucleotide polymorphisms located in the 5' region were associated with remission in fluvoxamine-treated outpatients with moderate to severe depression., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2014
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20. Changes in PR and QTc intervals after switching from olanzapine to risperidone in patients with stable schizophrenia.
- Author
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Suzuki Y, Sugai T, Ono S, Sawamura K, Fukui N, Watanabe J, Tsuneyama N, Saito M, and Someya T
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- Adolescent, Adult, Benzodiazepines therapeutic use, Cohort Studies, Electrocardiography, Female, Humans, Male, Middle Aged, Olanzapine, Risperidone therapeutic use, Sex Characteristics, Young Adult, Antipsychotic Agents adverse effects, Antipsychotic Agents therapeutic use, Benzodiazepines adverse effects, Heart Conduction System drug effects, Risperidone adverse effects, Schizophrenia drug therapy
- Abstract
Aim: We examined the difference between the effects of olanzapine (OLZ) and risperidone (RIS) on PR and QT intervals among patients with stable schizophrenia using a cohort analysis., Methods: Twenty-one subjects treated with OLZ were enrolled in the study. Following baseline assessments, which included PR and QT intervals, OLZ was switched to RIS for each subject. The same parameters were evaluated following the switch to RIS., Results: All patients who had been treated with OLZ were successfully switched to RIS. In all patients, we observed a significant decrease in PR interval (t = 2.397, P = 0.029) and no change in either QTc or RR interval. In female patients, the QTc interval was significantly decreased (t = 3.495, P = 0.008) following the switch, while in male patients, the QTc interval did not change. No patients showed a PR interval of >200 ms or a QTc interval of >500 ms., Conclusion: OLZ treatment has a greater prolonging effect on PR and QT intervals compared with RIS. Careful attention may need to be paid to the cardiac conduction system in addition to QT prolongation during OLZ treatment., (© 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.)
- Published
- 2014
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21. Effects of olanzapine on the PR and QT intervals in patients with schizophrenia.
- Author
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Suzuki Y, Ono S, Tsuneyama N, Sawamura K, Sugai T, Fukui N, Watanabe J, and Someya T
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- Adult, Antipsychotic Agents pharmacology, Benzodiazepines pharmacology, Electrocardiography, Electroencephalography, Female, Follow-Up Studies, Humans, Male, Olanzapine, Psychiatric Status Rating Scales, Young Adult, Antipsychotic Agents therapeutic use, Benzodiazepines therapeutic use, Heart Rate drug effects, Long QT Syndrome chemically induced, Schizophrenia drug therapy
- Published
- 2014
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22. High prevalence of underweight and undernutrition in Japanese inpatients with schizophrenia.
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Suzuki Y, Sugai T, Fukui N, Watanabe J, Ono S, Tsuneyama N, Saito M, and Someya T
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- Adolescent, Adult, Asian People psychology, Body Mass Index, Case-Control Studies, Humans, Inpatients psychology, Japan epidemiology, Male, Middle Aged, Obesity complications, Obesity epidemiology, Overweight complications, Overweight epidemiology, Prevalence, Schizophrenia epidemiology, Young Adult, Asian People statistics & numerical data, Inpatients statistics & numerical data, Malnutrition complications, Malnutrition epidemiology, Schizophrenia complications, Thinness complications, Thinness epidemiology
- Abstract
Aims: In Europe and North America, schizophrenia patients treated with antipsychotic agents have a higher prevalence of obesity and metabolic syndrome compared with healthy individuals. In Japan, the prevalence of overweight/obesity in the general population is considerably lower than that in Europe and North America. The purpose of this study was to investigate the prevalence of underweight and overweight/obesity as well as laboratory data in Japanese inpatients with schizophrenia., Methods: The subjects were 333 inpatients with schizophrenia and 191 age- and sex-matched healthy volunteers. Overweight/obesity was defined as body mass index (BMI) ≥ 25 kg/m(2) , standard weight was defined as BMI ≥ 18.5 to <25 kg/m(2) and underweight was defined as BMI < 18.5 kg/m(2) ., Results: A significant difference in the prevalence of the three BMI levels was observed between schizophrenia patients and controls (P < 0.001). The prevalence of underweight was significantly higher in schizophrenia patients than that in controls (P < 0.001). The prevalence of hypoproteinemia (P < 0.001) and of hypocholesterolemia (P < 0.001) were significantly higher in schizophrenia patients than in controls. In schizophrenia patients, the prevalence of hypotriglyceridemia was significantly higher in the underweight group than in the standard weight group (P = 0.003) and in the overweight/obesity group (P < 0.001)., Conclusions: The prevalence of underweight in Japanese inpatients with schizophrenia may be higher compared with that in the general population. Therefore, the physical health of inpatients should be more carefully taken into account in clinical practice., (© 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.)
- Published
- 2014
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23. The prevalence of glucose intolerance in Japanese schizophrenic patients with a normal fasting glucose level.
- Author
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Ono S, Suzuki Y, Fukui N, Sugai T, Watanabe J, Tsuneyama N, Saito M, and Someya T
- Subjects
- Adult, Biomarkers blood, Blood Glucose analysis, Chi-Square Distribution, Fasting blood, Female, Glucose Intolerance blood, Glucose Intolerance diagnosis, Glucose Tolerance Test, Humans, Inpatients, Japan epidemiology, Male, Middle Aged, Predictive Value of Tests, Prevalence, Schizophrenia blood, Schizophrenia diagnosis, Glucose Intolerance epidemiology, Schizophrenia epidemiology
- Abstract
Background: The prevalence of diabetes in patients with schizophrenia is 2- to 3-fold higher than in the general population. Glucose abnormalities were detected in 11.9% of Japanese schizophrenic patients in a recent cross-sectional study that included fasting glucose monitoring. However, detailed studies of glucose intolerance using the glucose tolerance test have been limited in Japanese patients with schizophrenia. We investigated the prevalence of abnormal glucose tolerance after glucose loading among Japanese inpatients with schizophrenia, with normal fasting glucose levels., Method: A total of 258 inpatients with schizophrenia participated in this study after giving their written informed consent. A 75-g oral glucose tolerance test was conducted in the morning after a 12-hour overnight fast., Results: Among patients with normal fasting glucose, 81.3% had normal glucose tolerance, 17.3% had impaired glucose tolerance, and 1.3% were diagnosed with diabetes., Conclusions: This study showed that the frequency of impaired glucose tolerance in patients with schizophrenia with normal fasting glucose levels might be higher than in the general population. Careful monitoring and screening of patients with schizophrenia for abnormal glucose metabolism might therefore be necessary.
- Published
- 2013
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24. Impact of the ABCB1 gene polymorphism on plasma 9-hydroxyrisperidone and active moiety levels in Japanese patients with schizophrenia.
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Suzuki Y, Tsuneyama N, Fukui N, Sugai T, Watanabe J, Ono S, Saito M, and Someya T
- Subjects
- ATP Binding Cassette Transporter, Subfamily B, Adult, Age Factors, Antipsychotic Agents pharmacokinetics, Antipsychotic Agents therapeutic use, Cytochrome P-450 CYP2D6 genetics, Female, Genotype, Humans, Japan, Male, Middle Aged, Paliperidone Palmitate, Polymorphism, Genetic, Regression Analysis, Risperidone therapeutic use, Young Adult, ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics, Isoxazoles pharmacokinetics, Pyrimidines pharmacokinetics, Risperidone pharmacokinetics, Schizophrenia drug therapy
- Abstract
9-Hydroxyrisperidone (9-OH-RIS) is an active metabolite of the antipsychotic drug risperidone (RIS). The total active moiety level, in other words the sum of the RIS and 9-OH-RIS serum levels, may be important for estimating the clinical effects of RIS treatment. However, there have been no consistent results reported regarding the relationship between cytochrome P450 (CYP) 2D6 or adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) variant alleles and 9-OH-RIS or total active moiety plasma levels. Seventy-four Japanese patients treated with RIS were examined in the present study. Steady-state plasma RIS and 9-OH-RIS were measured. The CYP2D6*5, CYP2D6*10, ABCB1 3435C>T, and ABCB1 2677G>T/A genotypes were detected. Multiple regression analysis showed that the dose-corrected plasma RIS levels were significantly correlated with the number of CYP2D6 variant alleles and ABCB1 3435C>T genotypes, whereas the 9-OH-RIS and total active moiety levels were significantly correlated with the ABCB1 3435C>T genotypes and with age. On the other hand, the ABCB1 2677G>T/A genotypes did not affect plasma RIS, 9-OH-RIS, or total active moiety levels. The ABCB1 3435C>T genetic polymorphism may predict plasma 9-OH-RIS and total active moiety levels.
- Published
- 2013
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25. Sex differences in the effect of four second-generation antipsychotics on QTc interval in patients with schizophrenia.
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Suzuki Y, Sugai T, Fukui N, Watanabe J, Ono S, Tsuneyama N, Saito M, and Someya T
- Subjects
- Adolescent, Adult, Aged, Antipsychotic Agents adverse effects, Aripiprazole, Benzodiazepines adverse effects, Benzodiazepines therapeutic use, Dibenzothiazepines adverse effects, Dibenzothiazepines therapeutic use, Electrocardiography, Female, Humans, Male, Middle Aged, Olanzapine, Piperazines adverse effects, Piperazines therapeutic use, Quetiapine Fumarate, Quinolones adverse effects, Quinolones therapeutic use, Risperidone adverse effects, Risperidone therapeutic use, Sex Factors, Young Adult, Antipsychotic Agents therapeutic use, Long QT Syndrome chemically induced, Schizophrenia drug therapy
- Abstract
Objective: We examined sex differences in the effect of olanzapine (OLZ), risperidone (RIS), aripiprazole (ARP), or quetiapine (QTP) on mean corrected QT (QTc) intervals among 222 patients with schizophrenia., Methods: Subjects were patients with schizophrenia who were treated with either OLZ (n = 69), RIS (n = 60), ARP (n = 62), or QTP (n = 31). Electrocardiographic measurements were conducted, and the QT interval was corrected using Bazett's correction formula., Results: The mean QTc interval of the QTP group was significantly longer than that of the RIS group (p = 0.002) or ARP group (p = 0.029). The mean QTc interval of the OLZ group was also significantly longer than that of the RIS group (p = 0.006). In female participants, the difference in the mean QTc interval among the four second-generation antipsychotic (SGA) groups was statistically significant (p = 0.002), whereas in male patients, there was no significant difference in the mean QTc interval among the four SGA groups. Post hoc analyses showed that sex differences in QTc interval were observed only in OLZ treatment group (p = 0.007)., Conclusion: To our knowledge, this is the first study to demonstrate sex differences in the effect of four SGAs on the QTc interval., (Copyright © 2013 John Wiley & Sons, Ltd.)
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- 2013
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26. Differences in plasma prolactin levels in patients with schizophrenia treated on monotherapy with five second-generation antipsychotics.
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Suzuki Y, Sugai T, Fukui N, Watanabe J, Ono S, Tsuneyama N, Saito M, and Someya T
- Subjects
- Adolescent, Adult, Aged, Antipsychotic Agents classification, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Regression Analysis, Time Factors, Young Adult, Antipsychotic Agents therapeutic use, Prolactin blood, Schizophrenia blood, Schizophrenia drug therapy
- Abstract
Although second-generation antipsychotics (SGAs) are characterized by fewer prolactin (PRL)-related side effects compared with first-generation antipsychotics, the detailed effects of SGAs on the plasma PRL levels still remain unclear. We examined the differences in plasma PRL levels among 268 patients treated for schizophrenia with olanzapine (OLZ), risperidone (RIS), aripiprazole (ARP), quetiapine (QTP), or perospirone (PER). The participants had received antipsychotic monotherapy with stable doses of OLZ, RIS, ARP, QTP, or PER for ≥ 3 weeks, and fasting blood samples were drawn to examine plasma PRL levels. The differences in median plasma PRL levels in all (P<0.001), male (P<0.001) and female patients (P<0.001) among the five SGA groups were statistically significant. A stepwise multiple regression analysis showed that ARP treatment was found to contribute to lower plasma PRL level, while female sex, RIS, OLZ and chlorpromazine equivalent dose were found to contribute to a higher plasma PRL level. The median value of plasma PRL level in the RIS group was twice as much compared with that in the OLZ group, although this was not statistically significant. In this study, OLZ had a considerable effect on plasma PRL level, similar to RIS, while PER did not affect plasma PRL levels, similar to QTP. Further studies are needed to clarify the differences in plasma PRL levels among SGAs., (Copyright © 2013 Elsevier B.V. All rights reserved.)
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- 2013
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27. Low prevalence of metabolic syndrome and its prediction in Japanese inpatients with schizophrenia.
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Suzuki Y, Sugai T, Fukui N, Watanabe J, Ono S, Tsuneyama N, Saito M, and Someya T
- Subjects
- Adult, Cholesterol, HDL blood, Female, Humans, Male, Metabolic Syndrome blood, Middle Aged, Predictive Value of Tests, Prevalence, Risk Factors, Schizophrenia blood, Schizophrenia drug therapy, Waist Circumference physiology, Antipsychotic Agents adverse effects, Asian People ethnology, Metabolic Syndrome chemically induced, Metabolic Syndrome ethnology, Schizophrenia ethnology
- Abstract
Objectives: There have so far been few papers studying the metabolic syndrome (MetS) prevalence rate in Japanese patients with schizophrenia. We studied the MetS prevalence rate in Japanese controls and inpatients with schizophrenia and compared the prediction factors for the occurrence of MetS., Methods: The subjects were 319 inpatients with schizophrenia and 154 controls. The predictive utilities of body mass index (BMI) and the individual components of MetS for MetS diagnosis were evaluated., Results: The prevalence of MetS did not differ between schizophrenia and control subjects. Subjects with schizophrenia showed higher prevalences of the MetS criteria for high-density lipoprotein cholesterol (HDL) (p < 0.001) and waist circumference (WC) (p < 0.001). In subjects with schizophrenia, the predictive power was found to be highest for HDL, followed by WC, BMI, triglyceride, diastolic blood pressure (BP), systolic BP and fasting plasma glucose. However, in control subjects, the predictive power was found to be highest for triglyceride, followed by WC, systolic BP, BMI, HDL, diastolic BP and fasting plasma glucose. HDL was the component most predictive of MetS in subjects with schizophrenia treated with antipsychotics., Conclusion: Because, in normal clinical practice, it is difficult to obtain temporal measurements for all of the MetS criteria, measurement of HDL may be useful for predicting the MetS., (Copyright © 2013 John Wiley & Sons, Ltd.)
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- 2013
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28. Changes in QT interval after switching to quetiapine in Japanese patients with schizophrenia.
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Suzuki Y, Sugai T, Fukui N, Watanabe J, Ono S, Tsuneyama N, Saito M, and Someya T
- Subjects
- Adult, Antipsychotic Agents pharmacology, Dibenzothiazepines pharmacology, Electrocardiography drug effects, Female, Heart Rate physiology, Humans, Male, Middle Aged, Quetiapine Fumarate, Schizophrenia ethnology, Schizophrenia physiopathology, Young Adult, Antipsychotic Agents therapeutic use, Asian People ethnology, Dibenzothiazepines therapeutic use, Drug Substitution methods, Heart Rate drug effects, Schizophrenia drug therapy
- Abstract
Objectives: There are few reports regarding quetiapine (QTP)-related QT prolongation. We examined the change in QT interval after switching from aripiprazole (ARP), olanzapine (OLZ), or risperidone (RIS) to QTP., Methods: Twenty subjects treated with ARP, OLZ, or RIS were enrolled in the study. Following baseline assessments, which included QT interval and electrolytes, these three drugs were switched to QTP for each subject. The same parameters were evaluated following a switch to QTP., Results: All 20 patients who had been treated with ARP, OLZ, or RIS were successfully switched to QTP. Significant increases were observed in the total mean corrected QT (QTc) interval after switching (p = 0.014). The coefficient of variation for the extent of change in QTc interval was 1.66. The mean QTc with ARP treatment was significantly increased after QTP treatment (p = 0.004)., Conclusions: Quetiapine might have a greater effect on QTc interval than other second-generation antipsychotics. However, because there was a considerable variability in the extent of QTc prolongation after switch to QTP, further studies are required to clarify the effect of QTP on QTc interval., (Copyright © 2012 John Wiley & Sons, Ltd.)
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- 2013
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29. Excessive insulin secretion in Japanese schizophrenic patients treated with antipsychotics despite normal fasting glucose levels.
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Sugai T, Suzuki Y, Fukui N, Watanabe J, Ono S, Tsuneyama N, and Someya T
- Subjects
- Adult, Antipsychotic Agents blood, Asian People ethnology, Blood Glucose drug effects, Female, Glucose Tolerance Test methods, Humans, Insulin blood, Insulin Resistance ethnology, Insulin Secretion, Male, Schizophrenia ethnology, Treatment Outcome, Antipsychotic Agents therapeutic use, Blood Glucose metabolism, Fasting blood, Insulin metabolism, Schizophrenia blood, Schizophrenia drug therapy
- Abstract
The development of impaired glucose tolerance induced by antipsychotics (APs) is of concern as a serious adverse effect of psychiatric drug therapy. However, the mechanism by which APs cause dysfunction of the glucose-insulin response is not fully understood. Recent studies have shown that patients treated with APs for schizophrenia were more likely to exhibit impaired glucose tolerance after a glucose load compared with healthy control subjects, even if fasting glucose levels were within the reference range. To explain these findings, we hypothesized that insulin secretion is increased in schizophrenic patients treated with AP, even those normal fasting glucose (NFG) levels. Therefore, oral glucose tolerance tests were conducted in 159 Japanese inpatients with AP-treated schizophrenia and in 90 healthy subjects without schizophrenia. Plasma glucose and serum insulin concentrations were measured before (0 minute) and at 30, 60, 90, and 120 minutes after the oral glucose load. Although insulin levels at 0 minute were similar in both groups of subjects, insulin levels were significantly higher in the patients treated with AP at all times after the glucose load than in the healthy subjects. In analyses of NFG subjects, insulin levels were significantly higher in the patients treated with AP compared with the healthy subjects at all times after glucose loading. Overall, we found that insulin secretion in response to a glucose load was significantly higher in the patients treated with AP, irrespective of NFG. These results suggest that APs affect the glucose-insulin response, which may lead to subclinical insulin resistance before the onset of overt glucose intolerance.
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- 2012
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30. Quetiapine-induced insulin resistance after switching from blonanserin despite a loss in both bodyweight and waist circumference.
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Suzuki Y, Sugai T, Fukui N, Watanabe J, Ono S, Tsuneyama N, Saito M, and Someya T
- Subjects
- Antipsychotic Agents therapeutic use, Dibenzothiazepines therapeutic use, Female, Homeostasis, Humans, Piperazines therapeutic use, Piperidines therapeutic use, Quetiapine Fumarate, Schizophrenia complications, Schizophrenia drug therapy, Young Adult, Antipsychotic Agents adverse effects, Dibenzothiazepines adverse effects, Insulin Resistance physiology, Piperazines adverse effects, Piperidines adverse effects, Waist Circumference drug effects, Weight Loss drug effects
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- 2012
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31. The lipid profiles in Japanese patients with schizophrenia treated with antipsychotic agents.
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Watanabe J, Suzuki Y, Sugai T, Fukui N, Ono S, Tsuneyama N, Saito M, and Someya T
- Subjects
- Adolescent, Adult, Aged, Body Mass Index, Case-Control Studies, Cholesterol, HDL blood, Cholesterol, LDL blood, Female, Humans, Japan, Male, Middle Aged, Schizophrenia blood, Young Adult, Antipsychotic Agents therapeutic use, Dyslipidemias chemically induced, Schizophrenia drug therapy
- Abstract
Objective: Antipsychotic-treated schizophrenia patients are susceptible to dyslipidemia. However, the results of previous studies of North American and UK populations including various races have been contradictory with regard to which lipid measure was the most affected in patients with schizophrenia taking antipsychotic agents. The aim of this study was to investigate the effect of schizophrenia patients receiving antipsychotic agents on each lipid measure in a Japanese population., Methods: The samples included 136 control individuals and 157 patients with schizophrenia treated with antipsychotic agents. Age, gender distribution and body mass index (BMI) of the controls were matched with the patients., Results: The high-density lipoprotein cholesterol (HDL-cholesterol) levels were significantly lower in patients than in the control subjects (P<.001). However, there were no significant differences in either the low-density lipoprotein cholesterol (LDL-cholesterol) or triglyceride levels between the patient and control groups. We performed a multiple linear regression analysis, and schizophrenia receiving antipsychotics was an independent predictor of decreased HDL-cholesterol. An increased BMI, male gender and cigarette smoking were also major predictors of a decreased HDL-cholesterol level (r(2)=0.42, P<.001)., Conclusion: At least in Japanese with schizophrenia receiving antipsychotic agents, the HDL-cholesterol levels should be closely monitored in all patients, even those who are not obese or do not smoke, to decrease their risk of cardiovascular disease., (Copyright © 2012 Elsevier Inc. All rights reserved.)
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- 2012
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32. Improvement in quetiapine-induced hypoglycemia following a switch to blonanserin.
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Suzuki Y, Tsuneyama N, Sugai T, Fukui N, Watanabe J, Ono S, Saito M, and Someya T
- Subjects
- Female, Humans, Hypoglycemia chemically induced, Middle Aged, Quetiapine Fumarate, Antipsychotic Agents adverse effects, Antipsychotic Agents therapeutic use, Dibenzothiazepines adverse effects, Hypoglycemia drug therapy, Piperazines therapeutic use, Piperidines therapeutic use
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- 2012
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33. Dysregulation of adipocytokines related to second-generation antipsychotics in normal fasting glucose patients with schizophrenia.
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Sugai T, Suzuki Y, Fukui N, Ono S, Watanabe J, Tsuneyama N, and Someya T
- Subjects
- Adiponectin blood, Adolescent, Adult, Antipsychotic Agents therapeutic use, Benzodiazepines adverse effects, Benzodiazepines therapeutic use, Blood Glucose analysis, Cross-Sectional Studies, Diagnostic and Statistical Manual of Mental Disorders, Dibenzothiazepines adverse effects, Dibenzothiazepines therapeutic use, Down-Regulation drug effects, Female, Humans, Insulin Resistance, Male, Middle Aged, Olanzapine, Quetiapine Fumarate, Risperidone adverse effects, Risperidone therapeutic use, Schizophrenia immunology, Young Adult, Antipsychotic Agents adverse effects, Leptin blood, Schizophrenia blood, Schizophrenia drug therapy, Up-Regulation drug effects
- Abstract
Objective: The underlying mechanism for second-generation antipsychotic (SGA)-related glucose-lipid metabolic dysfunction is not fully understood. Recent studies have suggested a possible impact of SGAs on endocrine regulation, especially on adipocytokines. We examined the effect of each SGA on various adipocytokines in normal fasting glucose (NFG) subjects., Method: The study population comprised 113 Japanese inpatients with schizophrenia who were treated with olanzapine, risperidone, or quetiapine, and 123 healthy control (CONT) volunteers. All of the subjects were diagnosed with NFG. Plasma concentration of adiponectin, leptin, tumor necrosis factor α, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were compared between the SGA and CONT groups., Results: Second-generation antipsychotic subjects had significantly higher leptin levels in comparison to the CONT subjects. The plasma concentration of adiponectin, total cholesterol, and high-density lipoprotein cholesterol in the SGA subjects were significantly lower than those in the CONT subjects. There were no significant differences in tumor necrosis factor α, triglyceride, and low-density lipoprotein cholesterol levels between the 2 groups. In a stepwise multiple regression analysis, olanzapine was found to be a factor that contributed to decreased adiponectin levels, and the CONT subjects were detected to be a factor associated with lower leptin levels., Conclusions: The present study indicates the possibility that the administration of SGAs may affect adipocytokines in the NFG stage, excluding the impaired fasting glucose group, which is in the transition stage into diabetes mellitus.
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- 2012
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34. Improvement in QTc prolongation induced by zotepine following a switch to perospirone.
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Suzuki Y, Watanabe J, Sugai T, Fukui N, Ono S, Tsuneyama N, Saito M, and Someya T
- Subjects
- Antipsychotic Agents administration & dosage, Antipsychotic Agents therapeutic use, Dibenzothiepins administration & dosage, Dibenzothiepins therapeutic use, Electrocardiography drug effects, Female, Haloperidol therapeutic use, Heart Rate drug effects, Humans, Isoindoles administration & dosage, Middle Aged, Schizophrenia drug therapy, Thiazoles administration & dosage, Water-Electrolyte Imbalance blood, Water-Electrolyte Imbalance chemically induced, Antipsychotic Agents adverse effects, Dibenzothiepins adverse effects, Isoindoles therapeutic use, Long QT Syndrome chemically induced, Thiazoles therapeutic use
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- 2012
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35. Increased risk of antipsychotic-related QT prolongation during nighttime: a 24-hour holter electrocardiogram recording study.
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Watanabe J, Suzuki Y, Fukui N, Ono S, Sugai T, Tsuneyama N, and Someya T
- Subjects
- Adult, Antipsychotic Agents therapeutic use, Benzodiazepines therapeutic use, Death, Sudden, Cardiac etiology, Death, Sudden, Cardiac prevention & control, Female, Humans, Male, Middle Aged, Olanzapine, Risperidone therapeutic use, Schizophrenia diagnosis, Torsades de Pointes chemically induced, Torsades de Pointes diagnosis, Antipsychotic Agents adverse effects, Benzodiazepines adverse effects, Circadian Rhythm drug effects, Electrocardiography, Ambulatory drug effects, Long QT Syndrome chemically induced, Risperidone adverse effects, Schizophrenia drug therapy, Schizophrenic Psychology, Signal Processing, Computer-Assisted
- Abstract
Most antipsychotic agents can cause QT prolongation, which causes torsades de pointes. The QT interval in healthy subjects is longer during nighttime than during daytime. The QT interval of patients treated with antipsychotics may be prolonged during nighttime, and the effects of antipsychotics on the QT interval may differ between antipsychotics. This study investigated the circadian dynamics of the QT interval in patients treated with antipsychotics and healthy controls, using a 24-hour Holter electrocardiogram in a clinical setting. Sixty-six patients with a diagnosis of schizophrenia that were treated with risperidone or olanzapine and 40 healthy volunteers were enrolled. The QT intervals were corrected using the Fridericia formula (QTcF = QT / RR). Mean ± SD nighttime QTcFs were 411.6 ± 29.0, 395.9 ± 21.2, and 387.8 ± 19.0 milliseconds (ms) in the risperidone, olanzapine, and control groups, respectively. The mean daytime QTcFs were 397.7 ± 23.4, 392.4 ± 18.9, and 382.6 ± 17.3 ms, respectively. The mean nighttime QTcF of the risperidone group was significantly longer than that of the olanzapine and control groups, although there was no significant difference in the mean daytime QTcF between the risperidone and olanzapine groups. The current study used 24-hour Holter electrocardiograms to reveal significantly longer QT intervals in the risperidone group especially during nighttime. In clinical practices, evaluations of the QT interval have been conducted over short periods in the daytime, but it is believed that such methods may not be able to fully elucidate the effects of antipsychotics on the QT interval.
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- 2012
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36. QT prolongation of the antipsychotic risperidone is predominantly related to its 9-hydroxy metabolite paliperidone.
- Author
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Suzuki Y, Fukui N, Watanabe J, Ono S, Sugai T, Tsuneyama N, Saito M, Inoue Y, and Someya T
- Subjects
- Adult, Age Factors, Antipsychotic Agents administration & dosage, Antipsychotic Agents pharmacokinetics, Dose-Response Relationship, Drug, Electrocardiography, Female, Humans, Isoxazoles pharmacokinetics, Male, Paliperidone Palmitate, Pyrimidines pharmacokinetics, Risperidone administration & dosage, Risperidone pharmacokinetics, Young Adult, Antipsychotic Agents adverse effects, Isoxazoles adverse effects, Long QT Syndrome chemically induced, Pyrimidines adverse effects, Risperidone adverse effects
- Abstract
Objective: A dose-dependent increase in risk of sudden cardiac death for the antipsychotic drug risperidone was reported. However, few reports have so far addressed QT prolongation associated with the use of risperidone or its major active metabolite, which is also used as a separate antipsychotic drug, paliperidone., Methods: The present study evaluated associations between risperidone metabolism and QT interval in 61 psychiatric patients who had been receiving risperidone for ≥4 weeks at an average dosage of 4.7 mg/day. Plasma risperidone and paliperidone levels were measured and electrocardiographic measurements were also obtained., Results: There was no correlation between risperidone dosage and QTc or plasma risperidone levels and QTc. However, there was a significant positive correlation between plasma paliperidone levels and QTc (r = 0.361; p = 0.004). There was no correlation between age and dose-corrected plasma risperidone levels or between age and QTc. There was a significant positive correlation between age and dose-corrected plasma paliperidone levels (r = 0.290; p = 0.023)., Conclusion: Clinically, paliperidone is considered to play a more important role in QT prolongation than risperidone., (Copyright © 2011 John Wiley & Sons, Ltd.)
- Published
- 2012
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37. Effect of the cytochrome P450 2D6*10 allele on risperidone metabolism in Japanese psychiatric patients.
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Suzuki Y, Fukui N, Tsuneyama N, Watanabe J, Ono S, Sugai T, Saito M, Inoue Y, and Someya T
- Subjects
- Adult, Alleles, Antipsychotic Agents metabolism, Female, Humans, Isoxazoles blood, Japan, Male, Middle Aged, Paliperidone Palmitate, Psychotic Disorders drug therapy, Pyrimidines blood, Risperidone metabolism, Schizophrenia drug therapy, Young Adult, Antipsychotic Agents pharmacokinetics, Cytochrome P-450 CYP2D6 genetics, Risperidone pharmacokinetics
- Abstract
Objective: The sum of the serum levels of risperidone (RIS) and 9-hydroxyrisperidone (9-OH-RIS), which is the active moiety serum level, could be important for estimating the clinical effects of RIS. However, there have been no consistent results reported about the relationship between cytochrome P450 (CYP) 2D6*10 allele and plasma 9-OH-RIS or active moiety levels. We investigated the effect of the number of CYP2D6*10 alleles on steady-state plasma RIS, 9-OH-RIS, and active moiety levels in Japanese patients., Methods: Steady-state plasma RIS, 9-OH-RIS, and active moiety levels were measured in 64 patients treated with an average dosage of 4.6 mg/day., Results: The number of CYP2D6*10 alleles significantly affected dose-corrected plasma RIS levels (p = 0.001), and the median concentrations in ng/ml/mg were 0.94 (0 allele) vs. 1.73 (1 allele) vs. 3.05 (2 alleles). The number of CYP2D6*10 alleles did not affect plasma 9-OH-RIS or active moiety levels., Conclusion: The present study shows that the number of CYP2D6*10 alleles affected plasma RIS levels but not plasma 9-OH-RIS and plasma active moiety levels. Because the plasma active moiety levels can influence antipsychotic effects or side effects, the genetic screening of the CYP2D6*10 allele for RIS in Asian populations may not be clinically important.
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- 2012
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38. Dose-dependent effects of olanzapine on QT intervals and plasma prolactin levels in Japanese patients with stable schizophrenia.
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Suzuki Y, Ono S, Sugai T, Fukui N, Watanabe J, Tsuneyama N, Sawamura K, and Someya T
- Subjects
- Adolescent, Antipsychotic Agents administration & dosage, Antipsychotic Agents therapeutic use, Benzodiazepines administration & dosage, Benzodiazepines therapeutic use, Body Mass Index, Dose-Response Relationship, Drug, Female, Humans, Japan, Male, Olanzapine, Prolactin blood, Psychiatric Status Rating Scales, Young Adult, Antipsychotic Agents adverse effects, Benzodiazepines adverse effects, Long QT Syndrome chemically induced, Prolactin drug effects, Schizophrenia drug therapy
- Abstract
Objectives: There have been few reports regarding olanzapine (OLZ)-related QT prolongation and hyperprolactinemia. This study evaluated the dose-dependent effect of OLZ on QT interval and plasma prolactin (PRL) level in a single sample of patients with schizophrenia., Methods: Twenty-six subjects treated with varying starting doses of OLZ were enrolled in the study. Following baseline assessments, which included completion of the Brief Psychiatric Rating Scale (BPRS), measurements of Body Mass Index (BMI), QT interval, electrolytes, fasting plasma glucose, PRL, hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), and low density lipoprotein (LDL), the dose of OLZ was increased for each subject. The same parameters were evaluated following the increased dose treatment., Results: A significant decrease was observed in BPRS score (p = 0.01) following treatment with an increased dose of OLZ. Significant increases were observed in BMI (p = 0.032), QTc (p = 0.031), and plasma PRL level (p = 0.028). The mean values of electrolytes, fasting plasma glucose, HbA1c, TC, TG, HDL and LDL treatment were unchanged by the switch to increased-dose OLZ treatment., Conclusion: We have demonstrated the dose-dependent effect of OLZ on the QT interval and the plasma PRL level of patients with schizophrenia., (Copyright © 2011 John Wiley & Sons, Ltd.)
- Published
- 2011
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39. Changes in the metabolic parameters and QTc interval after switching from olanzapine to aripiprazole in Japanese patients with stable schizophrenia.
- Author
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Suzuki Y, Sugai T, Ono S, Sawamura K, Fukui N, Watanabe J, Tsuneyama N, and Someya T
- Subjects
- Adolescent, Adult, Aripiprazole, Benzodiazepines pharmacokinetics, Female, Heart Rate drug effects, Humans, Male, Middle Aged, Olanzapine, Piperazines pharmacokinetics, Quinolones pharmacokinetics, Schizophrenia drug therapy, Schizophrenia physiopathology, Young Adult, Asian People, Benzodiazepines therapeutic use, Drug Substitution, Heart Rate physiology, Piperazines therapeutic use, Quinolones therapeutic use, Schizophrenia metabolism
- Published
- 2011
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40. Dose-dependent increase in the QTc interval in aripiprazole treatment after risperidone.
- Author
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Suzuki Y, Ono S, Fukui N, Sugai T, Watanabe J, Tsuneyama N, and Someya T
- Subjects
- Adult, Antipsychotic Agents therapeutic use, Aripiprazole, Dose-Response Relationship, Drug, Humans, Male, Piperazines therapeutic use, Quinolones therapeutic use, Risperidone therapeutic use, Antipsychotic Agents adverse effects, Arrhythmias, Cardiac chemically induced, Electrocardiography, Piperazines adverse effects, Quinolones adverse effects, Risperidone adverse effects
- Published
- 2011
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41. Differences in clinical effect and tolerance between fluvoxamine and paroxetine: a switching study in patients with depression.
- Author
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Suzuki Y, Tsuneyama N, Fukui N, Sugai T, Watanabe J, Ono S, and Someya T
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Treatment Outcome, Young Adult, Depression drug therapy, Depressive Disorder drug therapy, Drug Substitution, Fluvoxamine adverse effects, Fluvoxamine therapeutic use, Paroxetine adverse effects, Paroxetine therapeutic use
- Abstract
Objective: We examined whether discontinuation and the responses to fluvoxamine (FLV) administration could predict the subsequent discontinuation and the responses to paroxetine (PRX) in patients with depression., Methods: The subjects comprised 106 outpatients who were diagnosed with depression, and clinical evaluation was conducted every 2 weeks. Patients who discontinued FLV because of side effects or did not achieve remission with 200 mg/day of FLV, the drug was switched to PRX. The maximum dose of PRX was 40 mg/day., Results: Among 10 patients who discontinued FLV, PRX was also discontinued in one patient. Of 33 patients without remission on FLV, PRX was discontinued because of side effects in two patients. There was no statistical difference in the discontinuation rates between the two groups. Four of 10 patients who discontinued FLV achieved remission, while nine of 33 patients without remission with FLV achieved remission with PRX. The remission rate was not significantly different between the two groups., Conclusion: Discontinuation and the responses related to FLV could not serve as a predictor for the subsequent discontinuation and the responses related to PRX., (Copyright © 2010 John Wiley & Sons, Ltd.)
- Published
- 2010
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42. Gender differences in the relationship between the risperidone metabolism and the plasma prolactin levels in psychiatric patients.
- Author
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Suzuki Y, Fukui N, Watanabe J, Ono S, Sugai T, Tsuneyama N, Inoue Y, and Someya T
- Subjects
- Adult, Aged, Chromatography, Liquid methods, Enzyme-Linked Immunosorbent Assay methods, Female, Humans, Male, Mental Disorders drug therapy, Middle Aged, Paliperidone Palmitate, Prolactin blood, Tandem Mass Spectrometry methods, Young Adult, Isoxazoles blood, Mental Disorders metabolism, Pyrimidines blood, Risperidone metabolism, Risperidone therapeutic use, Sex Characteristics
- Abstract
Background: Risperidone (RIS) has the highest propensity to elevate plasma prolactin (PRL) levels. While the active metabolite 9-hydroxy-risperidone (9-OH-RIS) plays a predominant role in the efficacy and side effects of RIS, the mechanistic details are still poorly understood. The present study evaluated the gender differences in the relationship between plasma levels of RIS or 9-OH-RIS and PRL., Methods: Twenty-one male and 19 female subjects treated with RIS were enrolled in the present series. All patients had been receiving RIS for at least 4 weeks at an average dosage of 4.7 mg/day. Plasma RIS, 9-OH-RIS and PRL levels were measured., Results: In the male patients, there was no correlation between the RIS dosage and plasma PRL levels, between plasma RIS levels and PRL levels, or between the plasma 9-OH-RIS levels and PRL levels. In the female patients, there was a significant positive correlation between the plasma 9-OH-RIS levels and PRL levels (rs=0.456, p=0.049). There was a trend toward a significant positive correlation between the RIS dosage and plasma PRL levels. There was no correlation between the plasma RIS levels and PRL levels., Conclusion: 9-OH-RIS is considered to play a more important role in PRL elevation than RIS, and a gender difference exists in the effect of 9-OH-RIS on PRL level., (Copyright © 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
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43. Increase in the risk of chlorpromazine-induced QT prolongation during nighttime: is a short-period ECG during daytime sufficient?
- Author
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Suzuki Y, Watanabe J, Ono S, Fukui N, Sugai T, Tsuneyama N, and Someya T
- Subjects
- Adult, Antipsychotic Agents adverse effects, Circadian Rhythm, Electrocardiography, Female, Humans, Chlorpromazine adverse effects, Long QT Syndrome chemically induced, Schizophrenia drug therapy
- Published
- 2010
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44. The wide variability of perospirone metabolism and the effect of perospirone on prolactin in psychiatric patients.
- Author
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Suzuki Y, Sawamura K, Ono S, Fukui N, Sugai T, Watanabe J, Tsuneyama N, Inoue Y, and Someya T
- Subjects
- Adult, Aged, Antipsychotic Agents blood, Antipsychotic Agents pharmacokinetics, Chromatography, High Pressure Liquid, Female, Humans, Immunoenzyme Techniques, Indoles blood, Isoindoles blood, Male, Middle Aged, Thiazoles blood, Individuality, Isoindoles pharmacokinetics, Prolactin blood, Schizophrenia drug therapy, Thiazoles pharmacokinetics
- Abstract
Background: Perospirone was developed in Japan and is used for the treatment of schizophrenia and related illnesses. The authors investigated the relationship between the dosage of perospirone and the plasma levels of perospirone and its active metabolite, ID15036, and also evaluated the impact of the plasma concentrations of perospirone and ID15036 on the plasma prolactin level to examine whether perospirone or ID15036 affected the dopamine D(2) blockade, in psychiatric patients treated with perospirone., Methods: The subjects consisted of 21 adults treated with perospirone (4-60 mg/day). The plasma perospirone and ID15036 levels were measured in 21 patients and serum prolactin levels were investigated in 10 male patients with schizophrenia., Results: The plasma ID15036 level was higher than the plasma perospirone, and a positive correlation was observed between the dosage of perospirone and the ID15036 levels (p=0.032). The 10 male patients showed a positive correlation between the plasma perospirone levels and plasma prolactin levels (r=0.688, p=0.028) and between the plasma ID15036 levels and prolactin levels (r=0.775, p=0.009)., Conclusion: The plasma levels of ID15036 may have a greater impact on the dopamine D(2) blockade than perospirone in patients treated with perospirone., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
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45. [Customized pharmacotherapies in schizophrenia].
- Author
-
Suzuki Y, Fukui N, Watanabe J, Ono S, Sugai T, Tsuneyama N, and Someya T
- Subjects
- Adult, Antidepressive Agents, Second-Generation adverse effects, Female, Glycolipids metabolism, Humans, Hyperprolactinemia chemically induced, Long QT Syndrome chemically induced, Male, Metabolic Syndrome chemically induced, Middle Aged, Polymorphism, Genetic, Receptors, Dopamine D2 genetics, Schizophrenia metabolism, Young Adult, Antidepressive Agents, Second-Generation therapeutic use, Fluvoxamine adverse effects, Fluvoxamine therapeutic use, Pharmacogenetics, Precision Medicine, Schizophrenia drug therapy, Schizophrenia genetics, Selective Serotonin Reuptake Inhibitors adverse effects, Selective Serotonin Reuptake Inhibitors therapeutic use
- Abstract
When predicting the effects of medication for psychiatric diseases and their side effects based on genetic information, there are many things to consider besides just genetic information, including the index to be evaluated. We have shown before that it is important to simultaneously analyze both pharmacokinetic factors such as the blood concentration and pharmacodynamic factors such as the site of drug action, when searching for genetic information that can be used to predict the treatment effects of fluvoxamine for depression and its side effects. For example, we have shown that there exists a specific concentration that can be used to predict remission in the treatment of depression with fluvoxamine (Fukui et al, 2008); however, it is considered that without a sufficient examination of such factors besides genetic information, it is difficult to predict the effects using just genetic information. On the other hand, the situation is more complex with medication for schizophrenia. Although it appears that consensus has been obtained in that the goal of medication for depression is remission, the goal of medication for schizophrenia is not clear and it cannot be said that prediction studies on the effects have been sufficiently conducted using genetic information. Therefore, at our facility, focusing on metabolic anomalies due to antipsychotics, QT prolongation, and hyperprolactinemia, which have become issues in recent years, a prediction study on side effects was conducted. Because such side effects can be quantified, in comparison with the effects study, it is advantageously simple to examine the relationship with genetic information. However, in the course of this study, we discovered that there was a gender difference in terms of glycolipid metabolic anomalies, that antipsychotics particularly extended the QT interval during nighttime, and that prolactine following the administration of antipsychotics temporally increased before declining again a few weeks later. We believe that when examining the relationship between side effects and genetic information, the genetic information may not be sufficiently utilized unless the analysis is performed after obtaining a better understanding of the characteristics of such side effects.
- Published
- 2010
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