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ABSTRACT: BACKGROUND: Obesity is becoming more prevalent and thus growing as a public health concern in patients with schizophrenia. This investigation evaluated the relationship between body weight and the self-reported quality of life (QOL) of Japanese patients with schizophrenia. METHODS: We recruited outpatients (n=225) aged 42.5 +/- 12.8 (mean +/- SD) years with a DSM-IV diagnosis of schizophrenia who were admitted to psychiatric hospitals. This study used a cross-sectional design. The assessments included an interview to obtain sociodemographic data, the second version of the Short Form Health Survey (SF-36v2), the 10-item version of the Drug Attitude Inventory (DAI-10), the Clinical Global Impression-Severity (CGI-S) and height and weight measurements. SF-36v2 subscores were examined for differences based on the following body mass index (BMI) categories: healthy weight (BMI < 24.9), overweight (BMI 25--29.9) and obese (BMI > 30). A multiple regression analysis was employed to assess the relationship between these BMI categories and QOL outcomes. RESULTS: The overall prevalence of obesity in our sample was 16.4%. A multiple regression model revealed that age, gender, DAI-10 scores, CGI-S scores, social functioning, role emotional functioning, mental health, and Mental Composite Summary (MCS) score were significantly and positively associated with overweight status. Physical functioning, general health, role emotional functioning, mental health, and a physical composite summary (PCS) score were significantly and negatively associated with obesity. CONCLUSIONS: The burden of obesity is both a physical and a mental problem. An obesity intervention program for patients with schizophrenia may improve health-related QOL in patients with schizophrenia.
BMC Psychiatry 04/2013; 13(1):108. · 2.55 Impact Factor
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Norio Sugawara,
Norio Yasui-Furukori,
Takashi Umeda,
Shoko Tsuchimine,
Akira Fujii,
Yasushi Sato,
Manabu Saito, Hanako Furukori,
Kazuma Danjo,
Masashi Matsuzaka,
Ippei Takahashi,
Sunao Kaneko
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ABSTRACT: There have been a limited number of studies comparing bone mass between patients with schizophrenia and the general population. The aim of this study was to compare the bone mass of schizophrenia patients with that of healthy subjects in Japan.
We recruited patients (n = 362), aged 48.8 ± 15.4 (mean ± SD) years who were diagnosed with schizophrenia or schizoaffective disorder based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). Bone mass was measured using quantitative ultrasound densitometry of the calcaneus. The osteosono-assessment index (OSI) was calculated as a function of the speed of sound and the transmission index. For comparative analysis, OSI data from 832 adults who participated in the Iwaki Health Promotion Project 2009 was used as representative of the general community.
Mean OSI values among male schizophrenic patients were lower than those in the general population in the case of individuals aged 40 and older. In females, mean OSI values among schizophrenic patients were lower than those in the general community in those aged 60 and older. In an analysis using the general linear model, a significant interaction was observed between subject groups and age in males.
Older schizophrenic patients exhibit lower bone mass than that observed in the general population. Our data also demonstrate gender and group differences among schizophrenic patients and controls with regard to changes in bone mass associated with aging. These results indicate that intervention programs designed to delay or prevent decreased bone mass in schizophrenic patients might be tailored according to gender.
Annals of General Psychiatry 02/2012; 11:5. · 1.56 Impact Factor
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ABSTRACT: ABSTRACT:
Lifestyle factors, such as an unbalanced diet and lack of physical activity, may affect the prevalence of metabolic syndrome (MetS) in schizophrenic patients. The aim of this study was to compare the MetS prevalence between inpatients and outpatients among schizophrenic population in Japan.
We recruited inpatients (n = 759) and outpatients (n = 427) with a Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) diagnosis of schizophrenia or schizoaffective disorder from 7 psychiatric hospitals using a cross-sectional design. MetS prevalence was assessed using three different definitions, including the adapted National Cholesterol Education Program Adult Treatment Panel (ATP III-A).
The overall MetS prevalences based on the ATP III-A definition were 15.8% in inpatients and 48.1% in outpatients. In a logistic regression model with age and body mass index as covariates, being a schizophrenic outpatient, compared to being a schizophrenic inpatient, was a significant independent factor (odds ratio = 3.66 for males, 2.48 for females) in the development of MetS under the ATP III-A definition. The difference in MetS prevalence between inpatients and outpatients was observed for all age groups in males and for females over 40 years of age.
Outpatients with schizophrenia or schizoaffective disorder in Japan had a high prevalence of MetS compared to inpatients. MetS in schizophrenic outpatients should be carefully monitored to minimize the risks. A change of lifestyle might improve MetS in schizophrenic patients.
Annals of General Psychiatry 09/2011; 10:21. · 1.56 Impact Factor
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ABSTRACT: Smoking prevalence for schizophrenic patients is higher than for the general population. Inter-individual variability in hyperprolactinemia induced antipsychotics particularly risperidone can be explained by smoking status to some extent. We therefore studied the effects of smoking status on the plasma concentration of prolactin. Subjects included 154 schizophrenia patients (61 males, 93 females) who had received 3 mg of risperidone twice daily for at least 4 weeks. Sample collections were conducted 12 h after the bedtime dosing. The plasma concentrations of prolactin in the females were significantly higher than in the males (117.6±69.3 ng/ml vs. 52.9±30.7 ng/ml, p<0.001). The mean (±SD) plasma concentrations of prolactin did not differ between smokers and nonsmokers in the males (59.5±31.2 ng/ml vs. 47.6±29.3 ng/ml, not significant (ns)), but there was a significant difference in the females (100.2±59.1 vs. 134.0±74.6, ng/ml, p<0.05). Multiple regression analyses including gender, plasma drug concentration and age revealed that the plasma concentration of prolactin positively correlated with gender (standardized beta=0.452, p<0.001) and negatively with age (standardized beta=-0.171, p<0.05) and smoking status (standardized beta=-0.232, p<0.01). These findings suggest that smoking status has an impact on prolactin concentration during risperidone treatment. However, further study is required to determine whether these findings have clinical implications.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 01/2011; 35(2):573-6. · 3.25 Impact Factor
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Norio Sugawara,
Norio Yasui-Furukori,
Yasushi Sato,
Takashi Umeda,
Ikuko Kishida,
Hakuei Yamashita,
Manabu Saito, Hanako Furukori,
Taku Nakagami,
Mitsunori Hatakeyama,
Shigeyuki Nakaji,
Sunao Kaneko
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ABSTRACT: In an Asian population, the criteria for metabolic syndrome (MetS) are different from those for Western populations. The aim of this study was to assess the MetS prevalence among patients with schizophrenia or schizoaffective disorder in Japan.
We recruited patients (n=1186), aged 54.8±14.8 (mean±SD) years old with the DSM-IV diagnosis of schizophrenia or schizoaffective disorder who were admitted to seven psychiatric hospitals using a cross-sectional design. MetS prevalence was assessed by three different definitions, including the adapted National Cholesterol Education Program Adult Treatment Panel (ATP III-A). Comparative analysis was performed with schizophrenic subjects and 886 participants from the Iwaki Health Promotion Project 2008 as representative of general population.
The overall MetS prevalence based on the ATP III-A definition was 27.5%, with 29.8% in male and 25.3% in female patients. In a logistic regression model with age and body mass index as covariates, being schizophrenic was a significant independent factor (odds ratio=2.00 for males, 2.13 for females) in the development of MetS under the ATP III-A definition. The difference of MetS prevalence between patients and the general population was observed for those under 60 years of age.
Patients with schizophrenia or schizoaffective disorder in Japan had high prevalence of MetS compared to the general population, and was most apparent for those under 60 years of age. The MetS in schizophrenic patients should be carefully monitored to minimize the risks.
Biological Psychiatry 11/2010; 123(2-3):244-50. · 8.28 Impact Factor
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Ayako Kaneda,
Norio Yasui-Furukori,
Takashi Umeda,
Norio Sugawara,
Shoko Tsuchimine,
Manabu Saito,
Yasushi Sato, Hanako Furukori,
Ippei Takahashi,
Shigeyuki Nakaji,
Sunao Kaneko
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ABSTRACT: The Clock Drawing Test (CDT) is commonly used for cognitive screening, but there are few studies that compare performance on the CDT among schizophrenic patients of different ages. The objective of this study was to investigate the influence of schizophrenia and aging on performance in the CDT.
Schizophrenic patients (N = 244) and a comparison group (N = 875) were recruited as subjects. Freedman's CDT was completed by all subjects, and the influences of disease and aging on performance in the CDT were examined. Multiple comparisons of the CDT scores between patients and the comparison group and within three age subgroups (young: less than 40 years, middle aged: 40-59 years, elderly: more than 60 years) were performed.
There was a significant interaction of diagnosis and age, and the education significantly influenced the total score for all CDT conditions. For almost all age subgroups of patients, individuals with schizophrenia had significantly lower scores on all the CDT conditions than did the comparison group subjects. For patients and the comparison group, the elderly subgroup performed significantly worse than the young and middle-aged subgroups on almost all conditions of the CDT. Qualitative analysis of the clocks drawn revealed that the number of CDT categories in which schizophrenic patients scored significantly lower than the comparison group tended to increase with aging across both groups.
This study suggests that performance on the CDT was impaired not only by disease but also by aging. The study confirms that the CDT is sensitive enough to screen for cognitive impairments in schizophrenia.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 10/2010; 18(10):908-16. · 3.35 Impact Factor
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ABSTRACT: Several studies have suggested that risperidone is superior to olanzapine in glucose tolerance; however, there is little information available about the risk of impaired glucose metabolism induced by atypical antipsychotics in the same patients. A 75-g oral glucose tolerance test (OGTT) was performed in 22 mildly obese, diabetes-free, Japanese patients with schizophrenia who received risperidone or olanzapine for at least 2 months. After the OGTT, the medication was switched to another by decreasing the previous dosage gradually over 2 to 8 months after the initiation of the second medicine. After at least 8 weeks of complete switching, the same OGTT procedure was conducted. Fasting insulin concentration and the homeostasis model assessment of insulin resistance (HOMA-IR) during olanzapine treatment were significantly higher compared with risperidone treatment. The area under the concentration-time curves of serum insulin concentrations from 0 to 120 min was different in patients receiving risperidone compared with patients receiving olanzapine; however, there were no differences in the insulinogenic index between the two groups. The present study suggests that olanzapine might impair glucose tolerance to some extent because of an increase in insulin resistance compared with risperidone.
Experimental and Clinical Psychopharmacology 10/2010; 18(5):445-50. · 2.58 Impact Factor
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ABSTRACT: Hyperprolactinemia is a frequent consequence of treatment with risperidone. Recent studies have suggested that aripiprazole, a partial dopamine agonist, reduces the prolactin response to antipsychotics. Thus, we examined the dose effects of adjunctive treatment with aripiprazole on the plasma concentration of prolactin in patients who had elevated prolactin levels because of risperidone treatment. Aripiprazole was concomitantly administrated to 16 female patients with schizophrenia receiving 2 to 15 mg/d of risperidone. Dosages of aripiprazole were gradually increased from 3 to 12 mg/d with 2- to 4-week intervals. Sample collections for prolactin were conducted before aripiprazole administration (baseline) and 2 to 4 weeks after the dose escalation of aripiprazole and just before next dose escalation. The samples were taken just before the morning dose. The plasma concentration of prolactin during aripiprazole administration (3, 6, 9, or 12 mg/d) was significantly lower than that at baseline. The mean (±SD) percent reductions at 3, 6, 9, and 12 mg/d were 35% ± 14%, 54% ± 17%, 57% ± 19%, and 63% ± 17%, respectively. However, neither the plasma concentration of prolactin nor the reduction ratio differed among the dosages of 6, 9, and 12 mg/d of aripiprazole. Three out of 8 patients with amenorrhea improved after 12 mg/d of aripiprazole. The present study suggests that adjunctive treatment with aripiprazole reduces the prolactin concentration that had been increased because of risperidone treatment. The effect occurs even when a low dosage (3 mg/d) of aripiprazole was used and achieves a plateau at dosages beyond 6 mg/d.
Journal of clinical psychopharmacology 10/2010; 30(5):596-9. · 5.09 Impact Factor
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ABSTRACT: A tree-drawing test acts as both a projective psychological examination as well as a supplementary psychodiagnostic tool. There is little information relating the characteristics of schizophrenia and the tree-drawing test. The present study compared the structural and morphological differences in the results of the tree-drawing test between schizophrenic patients and healthy individuals, as well as between schizophrenic patients who responded well to treatment and those who responded poorly.
The subjects included 202 chronic schizophrenic patients and 113 healthy individuals. The schizophrenic patients were categorized as 'good responders' or 'poor responders' based on their response to medical treatments. The tree-drawing test was performed on all subjects. The tree drawn by each subject was analyzed structurally and morphologically.
There were significant differences between the trunk and branches drawn by schizophrenic patients and those drawn by healthy controls. There were no significant differences between the good responders and the poor responders in any aspect of the tree drawings. Multiple regression models showed that the ratio of the tree area to the total area of the drawing paper, the width of the trunk, the trunk base opening, and the size of the branch ends were significantly associated with schizophrenia.
The present study suggests that the trees drawn by schizophrenic patients are significantly different from those drawn by healthy individuals, but among schizophrenic patients, it is difficult to distinguish between good responders and poor responders using the tree-drawing test.
Psychiatry and Clinical Neurosciences 04/2010; 64(2):141-8. · 2.13 Impact Factor
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ABSTRACT: Hyperprolactinemia is a frequent consequence of treatment with some antipsychotic agents. Although prolactin secretion varies over the course of a day and during psychological circumstances, there is little information in the literature regarding the time dependence of the prolactin response to antipsychotics. We evaluated prolactin levels in schizophrenic patients receiving risperidone (3 mg twice daily), olanzapine (10 mg twice daily), or perospirone (16 mg twice daily) for at least 4 weeks. The subjects were compared to matched healthy controls. Plasma sample collection for quantification of drug and prolactin levels was conducted before and 2, 4, 6, 8, and 12 h after the morning dosing. Prolactin concentrations before dosing during risperidone treatment were significantly higher than during treatment with olanzapine and perospirone in females. The daily fluctuation of prolactin concentration after perospirone treatment was larger than that observed after risperidone and olanzapine treatments. Areas under the plasma concentration-time curves was greatest in subjects treated with risperidone, followed by perospirone and finally by olanzapine. These findings suggest that daily fluctuations in prolactin concentration after perospirone treatment are larger than following treatment with risperidone and olanzapine. The plasma concentration of prolactin during perospirone treatment therefore depends on the time of sampling.
Human Psychopharmacology Clinical and Experimental 04/2010; 25(3):236-42. · 2.48 Impact Factor
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ABSTRACT: Hyperprolactinemia is a frequent consequence of treatment with antipsychotic agents, partially because the prolactin response to antipsychotics is related to dopamine blockade. Recent studies have suggested that the prolactin response to olanzapine is weaker than that to risperidone. Thus, we studied the effects of various factors on the elevated plasma prolactin levels caused by these medications. The subjects were 94 patients with acutely exacerbated schizophrenia (46 males, 48 females). For four weeks, they received 6mg of risperidone and 20mg of olanzapine daily. Plasma samples were collected before the medications were given and 12h after the bedtime dosing each week. Treatment with either risperidone or olanzapine boosted plasma prolactin levels above baseline in both males and females. Prolactin levels were significantly higher in females than in males at all sampling points in both treatments. Risperidone increased prolactin significantly more than did olanzapine in both males and females. Delta prolactin (prolactin level at four weeks minus the baseline prolactin level) during olanzapine treatment significantly correlated with olanzapine concentration at 4th week (r=-0.518, p<0.01) only in males. Multiple regression analyses showed that delta prolactin during risperidone was significantly correlated with gender (p<0.001) and age (p<0.05) and that delta prolactin during olanzapine significantly correlated with gender (p<0.001) and drug concentration (p<0.01). The present study suggests that the predominant factors influencing hyperprolactinemia are young female for risperidone treatment, and being female and lower drug concentration as a predictor for hyperprolactinemia under olanzapine.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 02/2010; 34(3):537-40. · 3.25 Impact Factor
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ABSTRACT: Atypical antipsychotics are increasingly replacing conventional neuroleptic agents, but induction of impaired glucose tolerance and development of type 2 diabetes are of concern as side effects. Risperidone has been suggested to be superior to olanzapine for glucose tolerance in whites, but there is little information on these drugs in Asian populations, even though Asians have a higher risk of type 2 diabetes compared to whites.
A 75-g oral glucose tolerance test (OGTT) was performed in 100 age-matched, sex-matched, and body mass index (BMI)-matched Japanese inpatients with schizophrenia (DSM-IV criteria) who did not suffer from diabetes and had taken risperidone (N=50) or olanzapine (N=50) for at least 3 months. Subjects were from 1 university hospital and 3 mental hospitals in Japan; data were collected from April 2005 to March 2006. The same test was performed in 50 age-matched, sex-matched, and BMI-matched healthy Japanese subjects. Plasma glucose and serum insulin concentrations were measured just before loading (0 minutes) and 30, 60, and 120 minutes after oral glucose loading, and sorbitol levels in red blood cells were assayed at 0 and 120 minutes.
The fasting glucose level and insulin concentration did not differ among the risperidone, olanzapine, and control groups, but the areas under the concentration time curves for plasma glucose and serum insulin concentrations from 0 to 120 minutes in patients receiving risperidone or olanzapine were significantly higher (p<.05) than those for healthy controls. However, neither the insulinogenic index nor homeostasis model assessment of insulin resistance differed among the 3 groups. Sorbitol in red blood cells was significantly higher (p<.05) in both patient groups compared to the control group.
Olanzapine and risperidone may impair glucose tolerance due in part to increased insulin resistance. However, neither drug influenced insulin secretion in Japanese patients, and, therefore, these findings do not necessarily imply that atypical antipsychotics are directly associated with a risk of impairment of glucose tolerance.
The Journal of Clinical Psychiatry 12/2008; 70(1):95-100. · 5.80 Impact Factor
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ABSTRACT: Augmentation with paroxetine (10-40 mg/d) for antipsychotic treatment may improve the negative symptoms in schizophrenic patients but involves a risk of drug-drug interaction. We studied the effects of paroxetine on plasma concentrations of risperidone and 9-hydroxyrisperidone and their clinical symptoms in risperidone-treated patients. Twelve schizophrenic inpatients with prevailingly negative symptoms receiving risperidone 4 mg/d were, in addition, treated with incremental doses of paroxetine for 12 weeks (10, 20, and 40 mg/d for 4 weeks each). Plasma concentrations of risperidone and 9-hydroxyrisperidone were quantified with liquid chromatography-mass spectrometry mass-mass spectrometry together with clinical assessments before and after each phase of the 3 paroxetine doses. Risperidone concentrations during coadministration of paroxetine 10, 20, and 40 mg/d were 3.8-fold (95% confidence interval, 3.2-5.8, P < 0.01), 7.1-fold (95% confidence interval, 5.3-16.5, P < 0.01), and 9.7-fold (95% confidence interval, 7.8-22.5, P < 0.01) higher than that before paroxetine coadministration, respectively. Active moiety (risperidone plus 9-hydroxyrisperidone) concentration was not increased during the paroxetine 10 mg/d (1.3-fold, not significant) or 20 mg/d (1.6-fold, not significant), but were significantly increased by 1.8-fold (95% confidence interval, 1.4-2.7, P < 0.05) during the paroxetine 40 mg/d. Significant improvement in negative symptoms was observed from 10 to 40 mg/d of paroxetine, whereas scores in extrapyramidal side effects during 20 and 40 mg/d of paroxetine were significantly higher than baseline score. This study indicates that paroxetine increases plasma risperidone concentration and active moiety concentration in a dose-dependent manner. Low-dose coadministration of paroxetine with risperidone may be safe and effective in the treatment of schizophrenic patients with negative symptoms.
Journal of Clinical Psychopharmacology 01/2006; 25(6):527-32. · 4.10 Impact Factor
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ABSTRACT: The authors investigated steady-state pharmacokinetics of perospirone and its active metabolite hydroxyperospirone (ID-15036) and its prolactin response in 10 schizophrenic patients receiving 16 mg twice daily. Plasma concentrations of perospirone, hydroxyperospirone, and prolactin were monitored just before and up to 12 hours after the dosing. Thereafter, the dose was decreased to 8 mg twice daily in 8 patients, and drug concentrations were determined. The geometric means of peak concentration (Css(max)), time to Css(max) (tmax), area under the plasma concentration-time curve from 0 to 12 hours [AUC (0-12)], and elimination half-life at steady state were 8.8 ng/mL, 0.8 hours, 22.0 ng x h/mL, and 1.9 hours, respectively, for perospirone, and those of Css(max), tmax, and AUC (0-12) for hydroxyperospirone were 29.4 ng/mL, 1.1 hours, and 133.7 ng x h/mL, respectively. There were no differences in dose-normalized Css(max) or AUC (0-12) perospirone and hydroxyperospirone between 16 mg/day and 32 mg/day of perospirone. Changes in prolactin concentration from 1 to 2 hours after the dosing were parallel with drug concentrations, and almost normal ranges of prolactin concentration were observed before the morning dose despite steady state. The current study indicated that perospirone is rapidly absorbed and rapidly eliminated, which influences the prolactin response. The active metabolite hydroxyperospirone may play an important role in the antipsychotic effect because the plasma concentration of this metabolite is higher than that of the parent compound.
Therapeutic Drug Monitoring 09/2004; 26(4):361-5. · 2.49 Impact Factor
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ABSTRACT: The authors have developed and verified the precision and accuracy of new automated cloned enzyme donor immunoassays (CEDIA) for haloperidol and bromperidol, and cross-validations have been performed with conventional semiautomated EIA kits (MARKIT-M) and high-performance liquid chromatographic (HPLC) methods. The CEDIA method provides a quick (about 10 minutes) assay for haloperidol or bromperidol, requiring no serum/plasma pretreatment or predilution. The CEDIA haloperidol/bromperidol assay showed little or no cross reactivity with either their metabolites or many drugs commonly coprescribed. MARKIT-M revealed considerable cross reactivity values proportional to the spiked amounts of reduced metabolites. Precision, accuracy, recovery, and linearity testing for the CEDIA assay were all sufficient for clinical use. Significant linear correlations were found between CEDIA and HPLC in measuring haloperidol (CEDIA = 1.06 x HPLC + 0.869; n = 44, rs = 0.913, P < 0.001) and bromperidol (CEDIA = 1.06 x HPLC + 0.606; n = 56, rs = 0.914, P < 0.001) concentrations. This study has, therefore, demonstrated that the CEDIA assay has a quick run time with high precision and accuracy, and this method is a useful tool for the TDM of haloperidol or bromperidol.
Therapeutic Drug Monitoring 06/2004; 26(3):336-41. · 2.49 Impact Factor
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ABSTRACT: The effects of ginkgo supplementation on the steady-state plasma concentration of donepezil and the activity of cholinesterase in red blood cells and cognitive function were examined. Fourteen inpatients with Alzheimer's disease received donepezil 5 mg/day, supplemented with extracts of Ginkgo biloba 90 mg/day for 30 days. Blood samples were collected before and during ginkgo supplementation and 30 days after its discontinuation, together with an assessment of cognitive function. Plasma drug concentration was measured using high-performance liquid chromatography (HPLC), and cholinesterase in red blood cells was measured using Ellman methods. Cognitive function was evaluated using the Mini-Mental Scale Examination (MMSE). Plasma concentration of donepezil during ginkgo supplementation (mean +/- SD [95% confidence interval]; 24.4 +/- 12.6 ng/mL [17.1-31.7 ng/mL]) was not significantly different from that before ginkgo supplementation (22.7 +/- 10.3 ng/mL [16.8-28.7 ng/mL]) or that 4 weeks after its discontinuation (25.0 +/- 12.9 ng/mL [17.6-32.4 ng/mL]). There was no significant difference between cholinesterase in red blood cells before ginkgo supplementation (1.75 +/- 0.21 U [1.63-1.87 U]), during ginkgo supplementation (1.91 +/- 0.27 U [1.76-2.07 U]), and 4 weeks after its discontinuation (1.83 +/- 0.29 U [1.66-2.00 U]). Ginkgo supplementation did not alter MMSE scores throughout the study. The present study shows that ginkgo supplementation does not have major impact on the pharmacokinetics and pharmacodynamics of donepezil.
The Journal of Clinical Pharmacology 06/2004; 44(5):538-42. · 2.91 Impact Factor
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ABSTRACT: Therapeutic drug monitoring (TDM) services for plasma concentrations of haloperidol and bromperidol using enzyme immunoassay (EIA) methods are available in Japan, whereas high-performance liquid chromatographic (HPLC) methods are preferred in other countries. To compare these methods, we took 54 plasma samples for haloperidol and 91 plasma samples for bromperidol from schizophrenic patients receiving haloperidol or bromperidol, and the samples were measured using both commercial EIA and HPLC methods. Significant linear correlations were found between the two methods in determining haloperidol (EIA = 1.351 x HPLC + 1.39; r = 0.934, P < 0.001) and bromperidol (EIA = 1.420 x HPLC + 0.712; r = 0.956, P < 0.001) concentrations, but plasma concentrations using the EIA kits were approximately 92% (95% CI; 53-131%) and 62% (54-70%) higher than those using HPLC for haloperidol and bromperidol, respectively. Mean (and range) plasma concentrations of reduced metabolites were 54% (30-92%) and 55% (29-111%) of those of haloperidol and bromperidol, respectively. The present study suggests that reduced metabolites are included to a considerable degree in TDM data using the EIA kits. Therefore, some limitation of TDM data of haloperidol and bromperidol using the EIA kits, ie, high precision but poor accuracy, should be kept in mind.
Therapeutic Drug Monitoring 12/2003; 25(6):709-14. · 2.49 Impact Factor
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ABSTRACT: The effects of histamine H1-receptor antagonists, promethazine and homochlorcyclizine, both of which are inhibitors of CYP2D6, on the steady-state plasma concentrations (Css) of haloperidol and reduced haloperidol were studied in 23 schizophrenic inpatients receiving haloperidol, 12 to 36 mg/d, for 2 to 29 weeks. Promethazine, 150 mg/d, in 11 patients and homochlorcyclizine, 60 mg/d, in the others were coadministered for at least 1 week. Blood sampling was performed before and during coadministration of promethazine or homochlorcyclizine and 1 week after the discontinuation, together with clinical assessments by Brief Psychiatric Rating Scale (BPRS) and Udvalg for kliniske undersogelser (UKU) side effect rating scale. The Css (mean +/- SD) of haloperidol and reduced haloperidol during promethazine coadministration (27.6 +/- 24.9 and 8.6 +/- 13.2 ng/mL) were significantly higher than those before the coadministration (12.7 +/- 10.8 and 5.0 +/- 6.0 ng/mL; P < 0.01) or 1 week after the discontinuation (15.6 +/- 14.8 and 5.8 +/- 7.9 ng/mL; P < 0.05). The Css of haloperidol and reduced haloperidol during homochlorcyclizine coadministration (14.9 +/- 8.1 and 6.4 +/- 5.4 ng/mL) were also significantly higher than those before the coadministration (10.9 +/- 7.2 and 3.8 +/- 3.6 ng/mL; P < 0.01) or 1 week after the discontinuation (12.9 +/- 7.4 and 4.8 +/- 4.1 ng/mL; P < 0.05). No change in BPRS or UKU score was found throughout the study. Thus, the current study suggests that coadministration of clinical doses of promethazine and homochlorcyclizine increases the Css of haloperidol and reduced haloperidol via the inhibitory effects on the CYP2D6-catalyzed metabolism of haloperidol and reduced haloperidol.
Therapeutic Drug Monitoring 04/2003; 25(2):192-6. · 2.49 Impact Factor
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ABSTRACT: The effects of carbamazepine coadministration (400 mg/day for 1 week) on plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone were studied in 11 schizophrenic inpatients treated with 6 mg/day risperidone. Blood samplings were performed before and during carbamazepine coadministration, and 1 week after its discontinuation. Plasma concentrations of risperidone and 9-hydroxyrisperidone were measured using liquid chromatography-mass spectrometry-mass spectrometry. CYP2D6 genotypes were determined using the polymerase chain reaction method. Plasma concentrations of risperidone and 9-hydroxyrisperidone during carbamazepine coadministration (2.5+/-3.6 ng/ml and 19.4+/-4.1 ng/ml) were significantly ( P<0.01) lower than those before carbamazepine coadministration (5.0+/-7.9 ng/ml and 34.6+/-9.8 ng/ml). The changes in risperidone concentrations were positively correlated to the concentration ratios of risperidone/9-hydroxyrisperidone (r(s)=0.90, P<0.01), which were closely associated with CYP2D6 genotypes. The present study suggests that carbamazepine induces the metabolism of risperidone and 9-hydroxyrisperidone, and that the decrease in risperidone concentration is dependent on the CYP2D6 activity.
Psychopharmacologia 06/2002; 162(1):50-4. · 4.08 Impact Factor
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ABSTRACT: Therapeutic profiles of bromperidol and their relationship with plasma drug concentration and prolactin response were investigated in 30 acutely exacerbated schizophrenic patients treated with randomly allocated fixed-doses of bromperidol (6, 12 or 18 mg/day) for 3 weeks. The mean values (+/- S.D.) of percentage improvement at 3 weeks in total Brief Psychiatric Rating Scale (BPRS) and five subgrouped symptoms were 59.8+/-29.2% for total, 64.6+/-37.5% for positive, 73.3+/-33.7% for excitement, 80.2+/-45.5% for cognitive, 43.1+/-46.5% for negative and 49.6+/-46.8% for anxiety-depression symptoms, respectively. Twenty (67%) of 30 patients were responders defined as having 50% or more symptom reduction significantly greater in responders than those in nonresponders after 2 weeks. Mean plasma bromperidol concentration in patients with 50% or more reduction in positive symptoms was significantly higher than in the others (8.2+/-4.7 vs. 4.1+/-1.8 ng/ml, P< .05). Percentage improvement in total BPRS at 1 and 2 weeks were correlated well with that at 3 weeks. These findings suggest that an early improvement in positive and anxiety-depression symptoms results in favorable outcome of total response to bromperidol treatment. Plasma drug monitoring may have a limited predictive value for improvement in positive symptoms.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 01/2002; 26(1):53-7. · 3.25 Impact Factor
