Dietary patterns are associated with obesity in Japanese patients with schizophrenia.

BACKGROUND: Obesity among patients with schizophrenia is a growing concern because being overweight is widely regarded as a major risk factor for cardiovascular disease and premature death. Dietary patterns have been suggested as one modifiable factor that may play a role in development of obesity. The objective of this study was to examine the association between dietary patterns and obesity among patients with schizophrenia in Japan. METHODS: We recruited patients (n = 338) aged 44.0 ± 13.2 (mean ± SD) years with a DSM-IV diagnosis of schizophrenia who were admitted to four psychiatric hospitals using a cross-sectional design. Diet was assessed with a validated brief-type self-administered diet history questionnaire (BDHQ). Dietary patterns from 52 predefined food groups were extracted by principal component analysis. RESULTS: A total of 61 subjects (18.0%) were classified as obese. Three dietary patterns were identified: the healthy dietary pattern, the processed food dietary pattern, and the alcohol and accompanying dietary patterns. After adjusting for age and gender, patients within the high tertile of each healthy dietary pattern (OR = 0.29, 95% CI = 0.13 to 0.62) and processed food dietary pattern (OR = 0.44, 95% CI = 0.22 to 0.89) had a significantly lower risk for obesity compared with low tertile of dietary pattern. CONCLUSIONS: Our findings suggest that dietary patterns, including higher intake of protein, fat, n-3 polyunsaturated fatty acids, n-6 polyunsaturated fatty acids, and vitamins, may be related to a decreased prevalence of obesity within patients with schizophrenia. Future longitudinal research exploring dietary patterns and obesity among patients with schizophrenia is warranted.

Factors associated with the initiation of laxative use in the same patients with schizophrenia over a 20-year period: Retrospective cohort study.

BACKGROUND: Constipation is a common adverse effect of antipsychotics, but little investigation has been conducted. We aimed to address the factors associated with the initiation of laxative use in the same patients with schizophrenia over a 20-year period. METHODS: We enrolled patients with schizophrenia attending each hospital (n = 14) from April 1, 2021, and retrospectively examined all prescriptions as of April 1, 2016, 2011, 2006, and 2001, every 5 years starting in 2021, for this population. 716 participants with complete data were included in the analysis. The Cochran Q test followed by Bonferroni correction and the Cochran-Armitage trend test were used to determine the differences and trends of the frequency of each laxative. Multivariate logistic regression analysis was performed to assess the factors on the initiation of laxative use over a 20-year period. RESULTS: Of the patients, 25.1% were treated with laxatives in 2001, and 34.1% were treated in 2021. The numbers of patients treated with any laxatives significantly differed over the 20-year period, with a significant increasing trend. In all laxatives, the numbers of patients treated with magnesium oxide, lubiprostone and elobixibat differed with a significant increasing trend. Female sex, age, the total DZP equivalent dose, and the doses of levomepromazine maleate, olanzapine, quetiapine, zotepine, lithium, and carbamazepine in 2021 were significant factors associated with the initiation of laxative use over the 20-year period. CONCLUSIONS: Careful monitoring is needed for patients treated with levomepromazine maleate, olanzapine, quetiapine and zotepine. Optimizing prescriptions according to treatment guidelines could reduce antipsychotic-induced constipation.

Body mass index and quality of life among outpatients with schizophrenia in Japan.

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.

Prescribing Trends for the Same Patients with Schizophrenia Over 20 Years.

Background: Recent pharmacoepidemiology data show an increase in the proportion of patients receiving second-generation antipsychotic (SGA) monotherapy, but no studies have analyzed the same patients over a long period of time. Therefore, in this study, we retrospectively evaluated schizophrenia patients with available data for 20 years to determine whether the drug treatments in the same patients have changed in the past 20 years. Methods: The study began in April 2021 and was conducted in 15 psychiatric hospitals in Japan. Schizophrenia patients treated in the same hospital for 20 years were retrospectively examined for all prescriptions in 2016, 2011, 2006, and 2001 (ie, every 5 years). Results: The mean age of the 716 patients surveyed in 2021 was 61.7 years, with 49.0% being female. The rate of antipsychotic monotherapy use showed a slight increasing trend over the past 20 years; the rate of SGA use showed a marked increasing trend from 28.9% to 70.3% over the past 20 years, while the rate of SGA monotherapy use showed a gradual increasing trend over the past 20 years. The rates of concomitant use of anticholinergics, antidepressants, anxiolytics/sleep medications, and mood stabilizers showed decreasing, flat, flat, and flat trends over the past 20 years, respectively. Conclusion: The results of this study showed a slow but steady substitution of SGAs for first-generation antipsychotics (FGAs) over time, even in the same patients.

Effect of age and disease on bone mass in Japanese patients with schizophrenia.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Comparison of prevalence of metabolic syndrome in hospital and community-based Japanese patients with schizophrenia.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Different Attitudes of Patients and Psychiatrists Toward Benzodiazepine Treatment.

BACKGROUND: Concern regarding the benefit/risk ratio of the long-term use of benzodiazepines (BDZs) and Z-drugs is increasing. To prevent the risk of dependence in BDZ long-term use, it is essential to understand the attitudes of patients and psychiatrists toward BDZ treatment. The aims of this investigation were to 1) obtain information on patients' attitudes with long-term BDZ use and their referring psychiatrists' attitudes toward BDZ treatment, including their perception of the difficulty of reducing the dose of BDZs, and 2) identify discrepancies between patients' and psychiatrists' perceptions. METHODS: A brief questionnaire was constructed to investigate the attitudes of patients receiving BDZ treatment and their referring psychiatrists. Our sample comprised 155 patients who received BDZ treatment for more than one year and their referring eight psychiatrists. Both the patients and their psychiatrists completed our questionnaire between August 2017 and December 2017. RESULTS: Of the patients, 13% felt that it was more difficult to reduce the dose of BDZs than their referring psychiatrists (type A discrepancy), while 25% felt that it was less difficult (type B discrepancy). In the multivariate logistic regression analysis, the female sex and both the patients' ("psychotherapy plus BDZs was necessary" and "it was necessary to increase the dose of BDZs") and psychiatrists' beliefs ("short-term prescription was justified") were associated with type A discrepancies. Type B discrepancies were associated with psychiatrists' beliefs that the patient's wishes justified the use of BDZs and that the cessation of treatment with BDZs would lead to the deterioration of their rapport with their patients. CONCLUSION: To overcome the discrepancies in the attitudes of patients and psychiatrists toward the cessation of BDZ treatment, it is necessary to promote patient-centered care involving patient psychoeducation and practice guidelines for the decision-making process. Further studies investigating the promotion of patient-centered care to reduce BDZ use are needed.

Dose-dependent effects of adjunctive treatment with aripiprazole on hyperprolactinemia induced by risperidone in female patients with schizophrenia.

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.

Comparing the influences of age and disease on distortion in the clock drawing test in Japanese patients with schizophrenia.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Prolactin fluctuation over the course of a day during treatments with three atypical antipsychotics in schizophrenic patients.

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.

Characteristics of the tree-drawing test in chronic schizophrenia.

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Differences in etiological beliefs about schizophrenia among patients, family, and medical staff.

OBJECTIVES: To determine whether etiological beliefs are different among schizophrenia patients, their family, and medical staff. PATIENTS AND METHODS: A cross-sectional study was performed at five hospitals and one mental clinic and included 212 patients, 144 family members, and 347 medical staff other than psychiatrists. A questionnaire about the possible etiological causes of schizophrenia was used. RESULTS: There were significant differences in response scores among the three groups on using Angermeyer's and Goulding's classifications. Factor analyses revealed the following four subscales: Psychosocial, Biological, Environmental, and Cultural connotations. The structure varied among patients, family, and medical staff. CONCLUSION: The perspectives of schizophrenia etiology were different among patients, family, and medical staff.

Attitudes toward placebo-controlled clinical trials among depressed patients in Japan.

BACKGROUND: Placebo-controlled clinical trials are the standard in the design of clinical studies for the licensing of new drugs. Medical and ethical concerns regarding placebo use still exist in clinical trials of depressed patients. The aim of this study was to investigate the attitudes toward placebo-controlled clinical trials and to assess factors related to the willingness to participate in such trials among depressed patients in Japan. METHODS: A total of 206 depressed patients aged 49.5 ± 15.7 years (mean ± SD) who were admitted to three psychiatric hospitals were recruited for a cross-sectional study from June 2015 to March 2016. After a thorough explanation of the placebo, the study participants completed a brief 14-item questionnaire developed to evaluate patients' attitudes regarding possible participation in placebo-controlled clinical trials. The Quick Inventory of Depressive Symptomatology was also administered to assess depressive symptoms. RESULTS: The results indicated that 47% of the patients would be willing to participate in a placebo-controlled clinical trial. Expectations for the improvement of disease, desire to receive more medical care, encouragement by family or friends, and desire to support the development of new drugs were associated with the willingness to participate in such trials, whereas a belief that additional time would be required for medical examinations and fear of exacerbation of symptoms due to placebo use were associated with non-participation. LIMITATIONS: Patients were asked about possible participation in placebo-controlled clinical trials. CONCLUSIONS: Less than half of the respondents were willing to participate in placebo-controlled clinical trials. Attitudes toward participation in a placebo-controlled clinical trial need to be considered when deciding whether to conduct such a trial.

Work-family conflict as a mediator between occupational stress and psychological health among mental health nurses in Japan.

BACKGROUND: Occupational stress among mental health nurses may affect their psychological health, resulting in reduced performance. To provide high-quality, sustainable nursing care, it is necessary to identify and control the factors associated with psychological health among mental health nurses. The purpose of this study was to examine the role of work-family conflict (WFC) in the well-known relationship between occupational stress and psychological health among mental health nurses in Japan. METHODS: In this cross-sectional study, data were gathered from 180 mental health nurses who had a coresident child or were married. Data from the Work-Family Conflict Scale, the Generic Job Stress Questionnaire, the Maslach Burnout Inventory-General Survey, and the Center for Epidemiologic Studies for Depression Scale were obtained via self-report questionnaires. The effects of occupational stress and WFC on psychological health were explored by hierarchical linear regression analysis. RESULTS: The relationship between emotional exhaustion and occupational factors, including quantitative workload and the variance in workload, disappeared with the addition of WFC (each work interference with family [WIF] or family interference with work [FIW]). The relationship between emotional exhaustion and mental demands disappeared only with the addition of WIF. The relationship between depressive symptoms and variance in workload disappeared with the addition of WFC (each WIF or FIW). CONCLUSION: Our findings may encourage hospital administrators to consider the risks of medical staff WFC. Furthermore, longitudinal investigations into the factors associated with WFC are required for administrative and psychological interventions.

Relationship between occupational stress and depression among psychiatric nurses in Japan.

Psychiatric nursing is a stressful area of nursing practice. The purpose of this study was to examine occupational stress among psychiatric nurses in Japan. In this cross-sectional study, 238 psychiatric nurses were recruited from 7 hospitals. Data regarding the Generic Job Stress Questionnaire (GJSQ), the Center for Epidemiologic Studies for Depression Scale (CES-D), and the Health Practice Index (HPI) were obtained via self-report questionnaires. After adjusting for all the variables, CES-D scores were associated with job stress, but social support reduced the effect of stress on depression among psychiatric nurses. However, the interpretation of these results was hampered by the lack of data concerning important occupational factors, such as working position, personal income, and working hours. Further longitudinal investigation into the factors associated with depression may yield useful information for administrative and psychological interventions.

Hyperprolactinemia during antipsychotics treatment increases the level of coagulation markers.

OBJECTIVE: The strong association between psychiatric patients who receive antipsychotics and the incidence of venous thromboembolism (VTE) is known. Although previous reports suggest that hyperprolactinemia often increases markers of activated coagulation, few studies have examined the direct relationship between the prolactin level elevated by antipsychotics and activated markers of activated coagulation. METHOD: The participants included 182 patients with schizophrenia (male =89, female =93) who received antipsychotic treatments for at least 3 months. Markers of VTE (D-dimer, fibrin/fibrinogen degradation products, and thrombin-antithrombin complex) and serum prolactin concentrations were measured. RESULTS: Prolactin levels were significantly correlated with the logarithmic transformation of the D-dimer (r=0.320, P=0.002) and fibrin/fibrinogen degradation product levels (r=0.236, P=0.026) but not of the thrombin-antithrombin complex level (r=0.117, ns) among men. However, no correlations were found between the VTE markers and prolactin levels among women. These results were confirmed using multiple regression analyses that included demographic factors and antipsychotic dosages. CONCLUSION: The current study indicates that hyperprolactinemia is associated with an increase in markers of activated coagulation among men receiving antipsychotics. This finding clinically implies that monitoring and modulating prolactin levels among men are important to decrease the risk of VTE.

Attitudes toward Placebo-Controlled Clinical Trials of Patients with Schizophrenia in Japan.

BACKGROUND: Although the use of placebo in clinical trials of schizophrenia patients is controversial because of medical and ethical concerns, placebo-controlled clinical trials are commonly used in the licensing of new drugs. AIMS: The objective of this study was to assess the attitudes toward placebo-controlled clinical trials among patients with schizophrenia in Japan. METHOD: Using a cross-sectional design, we recruited patients (n = 251) aged 47.7±13.2 (mean±SD) with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder who were admitted to six psychiatric hospitals from December 2013 to March 2014. We employed a 14-item questionnaire specifically developed to survey patients' attitudes toward placebo-controlled clinical trials. RESULTS: The results indicated that 33% of the patients would be willing to participate in a placebo-controlled clinical trial. Expectations for improvement of disease, a guarantee of hospital treatment continuation, and encouragement by family or friends were associated with the willingness to participate in such trials, whereas a belief of additional time required for medical examinations was associated with non-participation. CONCLUSIONS: Fewer than half of the respondents stated that they would be willing to participate in placebo-controlled clinical trials. Therefore, interpreting the results from placebo-controlled clinical trials could be negatively affected by selection bias.

Dietary patterns and schizophrenia: a comparison with healthy controls.

BACKGROUND: It has been reported that the onset of schizophrenia and the physical complications after its onset are related to diet. Diet has been considered as a variable factor of the pathogenesis of schizophrenia. However, the results of studies on this relationship have been inconsistent. Nutrients are consumed as a mixture in the diet. It is difficult to study them in isolation because they may have mutually complementary effects. The aim of this study was to assess the association between dietary patterns and schizophrenia in Japan. METHODS: The subjects comprised 237 outpatients aged 30-60 years (123 males and 114 females) with diagnoses of either schizophrenia or schizoaffective disorder. The patient diagnoses were determined based on medical records. Patients were recruited between June 2011 and August 2011. As a reference group, 404 healthy volunteers aged 30-60 years (158 males and 246 females) were also included. Demographic data (age, sex, and level of education) were collected by face-to-face method interviews and self-administered questionnaires. We assessed eating habits over the last month using a validated brief self-administered diet history questionnaire. We detected dietary patterns through a principal component analysis of calorie-adjusted intake; two principal components were retained. The principal components for each dietary pattern and for each individual were divided into tertiles by principal component scores. RESULTS: We derived two dietary patterns by principal component analysis; namely, the "vegetable" dietary pattern and the "cereal" dietary pattern. In the "cereal" dietary pattern, the high tertile was associated with a significantly increased risk of schizophrenia (P<0.001). CONCLUSION: The "cereal" dietary pattern is associated with schizophrenia. This article is the first to describe a study examining the association of dietary pattern and schizophrenia.

Significant pharmacokinetic interaction between risperidone and carbamazepine: its relationship with CYP2D6 genotypes.

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.

The effects of Ginkgo biloba extracts on the pharmacokinetics and pharmacodynamics of donepezil.

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.