Tetsu Tomita

Effect of adjunctive treatment with aripiprazole to atypical antipsychotics on cognitive function in schizophrenia patients

Second-generation antipsychotics yield only a modest improvement in cognitive benefit compared to first-generation antipsychotics. Aripiprazole, which is a partial dopamine D2 receptor agonist, may have an impact on cognitive dysfunction in patients with schizophrenia. This study administered aripiprazole or placebo to 36 outpatients with schizophrenia also receiving risperidone or olanzapine for 12 weeks in a double-blind, randomized, placebo-controlled study. Cognitive function was evaluated using the Brief Assessment of Cognition in Schizophrenia (BACS) just prior to drug administration as well as 12 weeks after. The PANSS and UKU side effect rating scales were used to evaluate the clinical response to additional treatment with aripiprazole. In a primary analyses, ANCOVA showed that there was an interaction between the treatment group and time for verbal fluency (p < 0.05), but not for any domain in BACS, PANSS or UKU side effect rating scales. Upon secondary analysis, however, the ameliorative change in motor speed as assessed by the BACS (p < 0.05) for those receiving aripiprazole was greater than that for the placebo group, whereas deterioration in verbal fluency (p < 0.01) and executive function (p < 0.01) in those receiving aripiprazole was significantly greater than in the placebo group. These results suggest that adjunctive treatment with aripiprazole improves motor speed but worsens some cognitive functions. It is likely that these effects are due to the dopamine D2 antagonistic effect of aripiprazole.

Association between plasma paroxetine concentration and changes in plasma brain‐derived neurotrophic factor levels in patients with major depressive disorder.

Recent studies have implicated brain‐derived neurotrophic factor (BDNF) in the pathophysiology of depression and in the activities of antidepressant drugs. Serum BDNF levels are lower in depressed patients and increase in response to antidepressant medications; however, no studies have examined the association between plasma concentrations of antidepressant drugs and plasma BDNF levels. We assessed plasma BDNF levels and paroxetine concentrations in 45 patients with major depression who were being treated with paroxetine. Plasma samples were collected between 10:00 h and 12:00 h at baseline and after 1, 2 and 6 weeks of treatment. The BDNF level and paroxetine concentration of each sample were measured via enzyme immunoassay and high‐performance liquid chromatography, respectively. Plasma BDNF levels increased after 2 and 6 weeks of paroxetine treatment. Plasma BDNF levels were significantly lower in men than in women. Changes in plasma BDNF level were correlated with plasma drug concentration after 2 (r = 0.309, p < 0.05) and 6 weeks (r = 0.329, p < 0.05) but not correlated with plasma drug concentration after 1 week (r = 0.284, ns). Multiple regression analysis confirmed that this change was only significantly correlated with plasma paroxetine concentration after 2 (standardised beta = 0.343, p < 0.05) and 6 weeks (standardised beta = 0.375, p < 0.05). These results suggest that paroxetine treatment increases plasma BDNF levels and that plasma paroxetine levels play an important role in changes in plasma BDNF levels. Copyright

Sex-specific effects of subjective memory complaints with respect to cognitive impairment or depressive symptoms

The aim of this study was to investigate the association between subjective memory complaints (SMC) and sex.

Relationship between occupational stress and depression among psychiatric nurses in Japan

ABSTRACT 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.

Therapeutic reference range for plasma concentrations of paroxetine in patients with major depressive disorders.

Background: We investigated the relationship between plasma concentrations of paroxetine and the therapeutic effect of the drug, and we evaluated the therapeutic reference range for plasma concentration of paroxetine in patients with major depressive disorders (MDD). Methods: In this study, 120 patients with MDD were treated with 10–40 mg/d of paroxetine for 6 weeks, and 89 patients completed the protocol. The Montgomery–Asberg Depression Rating Scale (MADRS) was used to evaluate the patients at 0, 1, 2, 4, and 6 weeks. At the 6-week treatment time point, the patients were divided into 7 groups according to their paroxetine plasma concentrations in increments of 20 ng/mL. We used an analysis of variance and a &khgr;2 test to define the therapeutic reference range for plasma paroxetine concentrations. Results: We used 50% as the cutoff values for the percentage of MADRS improvement to determine the responder rates, and we defined remitters as patients with MADRS scores <10 at the 6-week treatment time point. We analyzed the responder and remitter rates of the patients according to their plasma paroxetine concentrations: 20 ng/mL, 40 ng/mL, and 60 ng/mL using the &khgr;2 test. According to the results of the &khgr;2 test in the responder rates, the 20–60 ng/mL plasma paroxetine group showed the highest effect size. Conclusions: The results of this study suggested that a range of 20–60 ng/mL is the therapeutic reference range for concentrations of paroxetine in plasma in patients with MDD.

The association between sunshine duration and paroxetine response time in patients with major depressive disorder

INTRODUCTION A recent study indicates that the serotonin transporter function varies with the duration of monthly sunshine. This finding may suggest that the efficacy of serotonin selective reuptake inhibitors (SSRIs) is associated with the duration of monthly sunshine, but information on this possible association is lacking. METHODS Ninety-one Japanese subjects with depression completed a 6-week treatment with paroxetine. Clinical evaluation was performed using the Montgomery and Asberg Depression Rating Scale (MADRS) before treatment and after 1, 2, 4 and 6 weeks of treatment. Data on the duration of monthly sunshine were obtained from the meteorological agency website. We divided the patients into four groups: nonresponders (NRs), later responders (LRs), early responders (ERs) and ultra-early responders (UERs). RESULTS The responses to paroxetine treatment of the group that began treatment in fall and winter and of the group that began treatment in spring and summer did not differ significantly. The effect of the duration of monthly sunshine on paroxetine response time did not differ significantly among the four groups, whereas the change in the duration of monthly sunshine had a significant effect on paroxetine response time. LIMITATIONS Our sample of patients with MDD was small and only included the Hirosaki area. CONCLUSION The change in the duration of monthly sunshine is associated with paroxetine response time.

Effect of depressive symptoms on the length of hospital stay among patients hospitalized for acute stroke in Japan.

Background Depression after stroke is one of the most serious complications of stroke. Although many studies have shown that the length of hospital stay (LOHS) is a measurable and important stroke outcome, research has found limited evidence concerning the effect of depression on LOHS among patients who have experienced acute stroke. The objective of this study was to assess the effect of depression on LOHS among patients hospitalized for acute ischemic stroke in Japan. Methods We retrospectively examined 421 patients who had experienced acute ischemic stroke. Stroke severity was measured by the National Institutes of Health Stroke Scale (NIHSS) on the 7th day of hospitalization. On the 10th day of hospitalization, depressive symptoms and functional assessment were assessed by the Japan Stroke Scale (Depression Scale) and the Functional Independence Measure, respectively. A general linear model was employed to assess the effect of probable depression on LOHS. Results The prevalence of probable depression in the current sample was 16.3% in males and 17.8% in females. The mean LOHS of participants with probable depression (76.4±49.2 days) was significantly longer than that of participants without probable depression (44.9±39.2 days). An analysis using the general linear model to assess the effect on LOHS revealed a significant interaction between the presence of probable depression and NIHSS scores. Conclusion Depression after stroke was associated with significant increases in LOHS. Early detection and treatment for depression are necessary for patients with ischemic stroke.

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.

Sex differences in the prediction of the effectiveness of paroxetine for patients with major depressive disorder identified using a receiver operating characteristic curve analysis for early response

Background We investigated cutoff values for the early response of patients with major depressive disorder to paroxetine and their sex differences by using a receiver operating characteristic (ROC) curve analysis to predict the effectiveness of paroxetine. Methods In total, 120 patients with major depressive disorder were enrolled and treated with 10–40 mg/day paroxetine for 6 weeks; 89 patients completed the protocol. A clinical evaluation using the Montgomery–Asberg Depression Rating Scale (MADRS) was performed at weeks 0, 1, 2, 4, and 6. Results In male subjects, the cutoff values for MADRS improvement rating in week 1, week 2, and week 4 were 20.9%, 34.9%, and 33.3%, respectively. The sensitivities and the specificities were 83.3% and 80.0%, 83.3% and 80.0%, and 100% and 90%, respectively. The areas under the curve (AUC) were 0.908, 0.821, and 0.979, respectively. In female subjects, the cutoff values for the MADRS improvement rating in week 1, week 2, and week 4 were 21.4%, 35.7%, and 32.3%, respectively. The sensitivities and the specificities were 71.4% and 84.6%, 73.8% and 76.9%, and 90.5% and 76.9%, respectively. The AUCs were 0.781, 0.735, and 0.904, respectively. Conclusion Early improvement with paroxetine may predict the long-term response. The accuracy of the prediction for the response is higher in male subjects.

An investigation of temperament and character inventory items for predicting the response to paroxetine treatment in patients with major depressive disorder.

BACKGROUND Previous studies have reported associations between Temperament and Character Inventory (TCI) dimension scores and the response to treatment in patients with major depressive disorder (MDD). We aimed to determine which TCI items could predict the response to treatment with paroxetine in patients with MDD. METHODS Seventy-three patients were enrolled in this study. The participants were treated with 10-40mg/day of paroxetine for six weeks; they then completed the TCI. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to evaluate the patients. The participants were divided into two groups (responders and non-responders). We used a chi-squared test to identify the 10 items with the strongest association with treatment response from among all 240 items on the TCI, and we used a multiple logistic regression analysis to confirm the validity of these 10 items. RESULTS Among the TCI dimension scores, only the C score differed significantly between the two groups. We analyzed 10 models using each of the 10 best items. All the models significantly predicted treatment response. The TCI dimensions model also significantly predicted treatment response, but its predictive value was lower than those of the other 10 models. LIMITATIONS The responders included the early responders. The results lacked information about responders whose responses were not predicted by the logistic regression models and TCI items. CONCLUSIONS Some TCI items showed significant associations with the response to paroxetine treatment in the patients with MDD. Treatment response in patients with MDD may be predicted using only 10 items from the TCI.