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The response to antidepressants varies significantly among individuals and is difficult to predict before treatment. In this randomised control trial, we explored cytokines that correlate with the therapeutic effect of mirtazapine (MIR) and selective serotonin reuptake inhibitors (SSRIs) and whether they could be predictors of remission for each antidepressant. Plasma cytokines, such as tumour necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were assayed in 95 participants before medication and assayed by the enzyme-linked immunosorbent assay. The Hamilton Rating Scale for Depression assessed depressive symptoms over 4 weeks. In the SSRI group, the baseline GM-CSF level was significantly higher in the remission group than in the non-remission group (p =.022). In the MIR group, the baseline level of TNF-α was significantly higher (p =.039) and IL-2 was lower (p =.032) in the remission group than in the non-remission group. In patients prescribed with MIR, the cut-off values of TNF-α (10.035 pg/mL) and IL-2 (1.170 pg/mL) calculated from the receiver operating characteristic curve suggested that the remission rate, which corresponds to a positive predictive value, could be increased from 31.3% to 60.0% and 50.0%, respectively. For those prescribed with SSRIs, the remission rate was 37.0% and using the cut-off value of GM-CSF (0.205 pg/mL), the remission rate could be almost doubled to 70%. Our study shows that pre-treatment plasma concentrations of TNF-α, IL-2, and GM-CSF may suggest the predictability of remission by SSRIs or MIR. [ABSTRACT FROM AUTHOR]

• This is the prospective follow-up study to predict further episodes of sick leave among Japanese workers. • Receiver operating characteristic curves were constructed for the SASS scores, correct response rates for the 3-back tasks, and use of diazepam equivalence, and the cut off points for these predictors were calculated. • The cut-off point was found to be 30/31 for the SASS score, 50% for the correct response rate for the 3-back task, and a 7.5 mg dose of diazepam equivalent for the use of a benzodiazepine. [ABSTRACT FROM AUTHOR]

Background: Polypharmacy of additional psychotropics alongside the main treatment drug (antipsychotics in schizophrenia and antidepressants in major depressive disorder) is common in Japan. Our goal is to align psychotropic prescription in Japan with international standards, while reducing the differences between facilities. To achieve this goal, we aimed to compare prescriptions at the time of hospital admission and discharge. Methods: Data on prescriptions at admission and discharge from 2016 to 2020 were collected. We divided the patients into four groups: (1) mono_mono group, monotherapy of the main drug at admission and discharge; (2) mono_poly group, monotherapy at admission and polypharmacy at discharge; (3) poly_poly group, polypharmacy at admission and discharge; and (4) poly_mono group, polypharmacy at admission and monotherapy at discharge. We compared the changes in dosage and number of psychotropics among the four groups. Results: For both schizophrenia and major depressive disorder, the patients who received monotherapy with the main drug at admission were likely to receive main drug monotherapy at discharge and vice versa. For schizophrenia, the polypharmacy was prescribed more often in the mono_poly group than that in the mono_mono group. The prescription was not changed at all for more than 10% of the patients. Conclusions: It is critical to avoid a polypharmacy regimen to ensure that guideline-compliant treatment is provided. We expect higher rates of monotherapy with the main drug after the EGUIDE lectures. Trial registration: The study protocol was registered in the University Hospital Medical Information Network Registry (UMIN000022645). [ABSTRACT FROM AUTHOR]

Aim: Treatment guidelines are designed to assist patients and health care providers and are used as tools for making treatment decisions in clinical situations. The treatment guidelines of the Japanese Society of Mood Disorders establish treatment recommendations for each severity of depression. The individual fitness score (IFS) was developed as a simple and objective indicator to assess whether individual patients are practicing treatment by the recommendations of the depression treatment guidelines of the Japanese Society of Mood Disorders. Methods: The EGUIDE project members determined the IFS through the modified Delphi method. In this article, the IFS was calculated based on the treatment of depressed patients treated and discharged between 2016 and 2020 at facilities participating in the EGUIDE project. In addition, we compared scores at admission and discharge. Results: The study included 428 depressed patients (mild n = 22, moderate/severe n = 331, psychotic n = 75) at 57 facilities. The mean IFS scores by severity were statistically significantly higher at discharge than at admission with moderate/severe depression (mild 36.1 ± 34.2 vs. 41.6 ± 36.9, p = 0.49; moderate/severe 50.2 ± 33.6 vs. 55.7 ± 32.6, p = 2.1 × 10–3; psychotic 47.4 ± 32.9 versus 52.9 ± 36.0, p = 0.23). Conclusion: We developed the IFS based on the depression treatment guideline, which enables us to objectively determine how close the treatment is to the guideline at the time of evaluation in individual cases. Therefore, the IFS may influence guideline‐oriented treatment behavior and lead to the equalization of depression treatment in Japan, including pharmacotherapy. [ABSTRACT FROM AUTHOR]

Aims: The Guidelines for the Pharmacotherapy of Schizophrenia were established to improve the quality of medical care, and the EGUIDE project was conducted to train clinicians on guideline usage. A quality indicator (QI) was established to measure the prevalence of the guidelines, and a survey was conducted, which revealed a gap between the guidelines and actual clinical practice (evidence‐practice‐gap). The purpose of this study was to develop an individual fitness score (IFS) formula that expresses the degree to which prescribers adhere to the Guidelines for Pharmacological Therapy of Schizophrenia in a simple manner, and to determine the validity of this formula from a survey of the prescriptions of the EGUIDE project participants'. Methods: To establish appropriate scores, members discussed the proposed formula and then voted on them. The IFS formula developed was set up so that antipsychotic monotherapy would be given 100 points, with points deducted if concomitant or adjunctive antipsychotic medications were used, and a minimum score of 0. To validate this formula, prescriptions of hospitalized schizophrenic patients at admission and at discharge were scored and compared. Result: IFS points vary and ranged from 0 to100. The average pre‐admission score for all subjects was 45.6, and the average score at discharge was 54, those were significantly higher during discharge. Conclusions: We developed an IFS formula, a tool to easily visualize the degree to which current prescriptions conform to the guidelines for the pharmacological treatment of schizophrenia. [ABSTRACT FROM AUTHOR]

Objective: We investigated the effects of a single instance of caffeine intake on neurocognitive functions and driving performance in healthy subjects using an established cognitive battery and a driving simulator system. Methods: This study was conducted in a double-blind, randomized, placebo-controlled manner from February 19, 2016 to August 6, 2016. Caffeine intake was discontinued 3 days prior to the study. Participants were randomly assigned to receive 200-mg doses of caffeine or a placebo. Thirty minutes after administration, cognitive functions were evaluated via the Symbol Digit Coding Test (SDC), the Stroop Test (ST), the Shifting Attention Test (SAT) and the Four Part Continuous Performance Test (FPCPT). After the cognitive function tests were conducted, driving performance was evaluated using a driving simulator. We measured the brake reaction time (BRT) in the Harsh-braking test and the standard deviation of the lateral position (SDLP) in the Road-tracking test. Results: Of 100 randomized subjects, 50 (50%) of 100 in the caffeine group and 50 (50%) of 100 in the placebo group completed the study. Participants in the caffeine group had more correct responses than participants in the placebo group on the SAT (P = 0.03) and made fewer errors (P = 0.02). Participants in the caffeine group exhibited shorter times in the Harsh-braking test than participants in the placebo group (P = 0.048). Conclusions: A single instance of caffeine intake changed some neurocognitive functions and driving performance in healthy volunteers. Trial registration: . [ABSTRACT FROM AUTHOR]

Objectives:Catecholamines, brain-derived neurotrophic factor (BDNF) and cytokines may be involved in the pathophysiology of schizophrenia. The aim of this study was to examine the associations between serum BDNF levels, plasma catecholamine metablolites, cytokines and the cognitive functions of patients with schizophrenia treated with atypical antipsychotic monotherapy. Methods:One hundred and forty-six patients with schizophrenia and 51 age- and sex-matched healthy controls were examined for peripheral biological markers and neurocognitive test. Results:There were positive correlations between serum BDNF levels and scores for verbal memory and attention and processing speed as well as between serum BDNF levels and negative symptoms. Furthermore, there was a negative correlation between the plasma homovanillic acid (HVA) level and motor function and a positive correlation between the plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) level and attention and processing speed. There were no significant correlations between interleukin-6 or tumour necrosis factor alpha and cognitive function. Moreover, there were no significant correlations between the plasma levels of HVA, MHPG, cytokines and clinical symptoms. Conclusions:Serum BDNF levels are positively related to the impairment of verbal memory and attention, plasma HVA levels are positively related to motor function, and plasma MHPG levels are positively related to attention in patients with schizophrenia. [ABSTRACT FROM PUBLISHER]

A letter to the editor is presented which discusses three case reports concerning the development and persistent of neutropenia in patients with treatment-resistant schizophrenia during electroconvulsive therapy (ECT).

In the present study, we aimed to investigate the difference in white matter between smokers and nonsmokers. In addition, we examined relationships between white matter integrity and nicotine dependence parameters in smoking subjects. Nineteen male smokers were enrolled in this study. Eighteen age-matched non-smokers with no current or past psychiatric history were included as controls. Diffusion tensor imaging scans were performed, and the analysis was conducted using a tract-based special statistics approach. Compared with nonsmokers, smokers exhibited a significant decrease in fractional anisotropy (FA) throughout the whole corpus callosum. There were no significant differences in radial diffusivity or axial diffusivity between the two groups. There was a significant negative correlation between FA in the whole corpus callosum and the amount of tobacco use (cigarettes/day; R = − 0.580, p = 0.023). These results suggest that the corpus callosum may be one of the key areas influenced by chronic smoking. [ABSTRACT FROM AUTHOR]

Abstract: Objective: This study sought to examine whether switching polypharmacy therapy to monotherapy would improve the cognitive function and social function of patients with schizophrenia. Methods: Thirty-nine patients with schizophrenia who were receiving therapy with two antipsychotics were randomly divided into a switch to monotherapy group (switching group) and a polypharmacy continued group (continuing group). For the patients allocated to the switching group, the dose level of one of the two antipsychotic drugs was gradually reduced to zero. Psychotic symptoms, cognitive function and social function scale scores were assessed immediately before and 24 weeks after switching, and the time courses of these scores were compared between the two groups. Results: Compared with the continuing group, the switching group demonstrated significantly greater improvement in attention after switching (p = 0.02). Furthermore, the improvement in daily living (p = 0.038) and work skills (p = 0.04) was significantly greater in the switching group. In an analysis of the correlation among sub-items with respect to the degrees of improvement, a significant correlation was noted between improvement in executive function and improvement in daily living (r = −0.64, p = 0.005) and between improvement in work skills and improvement in attention (r = −0.51, p = 0.038). Conclusion: In patients with schizophrenia receiving polypharmacy, switching to monotherapy resulted in improvements in attention. Furthermore, improvements in executive function led to improvements in daily living, and improvements in attention led to improvements in work skills. Thus, switching to monotherapy is a useful option. [Copyright &y& Elsevier]

Abstract: The association between smoking and psychiatric disorders (PD) has been known for many years. Support for smoking cessation among patients with PD is provided in advanced nations, but there is a little support for smoking cessation among patients with PD in Japan, where few studies have investigated the smoking rate. The aim of the present study is to determine the smoking rate and smoking habits of Japanese patients with PD. The subjects included outpatients who visited the outpatient psychiatric clinic at a University hospital between January and March of 2011. They answered a questionnaire consisting of questions about their sociodemographic background and smoking habits. In an analysis of 733 subjects, the overall smoking rate was 25.1%. The smoking rates among the patients with schizophrenia and depression were 17.3% and 23.9%, respectively, and these rates were lower than the results of previous studies. Among the current smokers, 43.4% had experienced smoking cessation, and only 26.1% were not interested in smoking cessation. Of the current smokers, 37.5% spent between US$128.88 and US$257 per month on cigarettes. [Copyright &y& Elsevier]

Objective We investigated the plasma levels of interleukin (IL)-6 and 5-HTT polymorphisms in patients with major depressive disorder (MDD). This is the first report, to our knowledge, of an investigation into the association between 5-HTT gene polymorphism, plasma IL-6 levels, and responses to selective serotonin reuptake inhibitors (SSRIs) in Japanese patients with MDD. Method One-hundred and eighteen patients (51 male, 67 female) who met the DSM-IV criteria for MDD were enrolled. Their ages ranged from 24 to 78 (mean ± SD = 44 ± 12) years. The patients were treated with SSRIs (paroxetine in 66 cases, sertraline in 42 cases) for 8 weeks. Results The plasma levels of IL-6 were significantly higher in the SSRI responders than in the nonresponders ( p = 0.0328), and the changes in plasma IL-6 levels correlated significantly with the changes in severity of depressive state ( p = .0.007). No difference was found in baseline and the changes in plasma IL-6 levels between the patients with a 5-HTT gene (5-HTTLPR) L-carrier and those with S/S. Conclusion These results suggest that the plasma levels of IL-6 reflect the severity of MDD and that plasma IL-6 levels might be another biological-state marker for the depressive state. In addition, the 5-HTTLPR polymorphism might be independent of plasma IL-6 levels. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: Electroconvulsive therapy (ECT) has proven to be effective in treatment-resistant depression (TRD). In recent reports, 70% to 90% of patients with TRD responded to ECT. However, post-ECT relapse Is a significant problem. There are no studies investigating risk factors associated with reintroducing ECT in depressive patients after remission previously achieved with former ECT. The aim of the present study is to examine such risk factors using a sample of TRD patients. Methods: We conducted a chart review to examine patient outcomes and adverse events over short- and long-term periods. Forty-two patients met the criteria for major depressive disorder. Results: The response rate was 85.7% (36/42). There were no significant differences in the baseline characteristics of patients exhibiting remission, response or non-response. The rate of adverse events was 21.4% (9/42). Among 34 patients who were available for follow-up, 18 patients relapsed (relapse rate, 52.9%), and 6 patients were reintroduced to ECT. The patients' age and age of onset were significantly higher In the re-ECT group than non re-ECT group. Conclusion: Our results suggest that older age and older age of onset might be considered for requirement of re-ECT after remission previously achieved with former ECT. [ABSTRACT FROM AUTHOR]

Objective We investigated the effects of aripiprazole on plasma levels of brain-derived neurotrophic factor (BDNF) and catecholamine metabolites in first-episode untreated schizophrenia patients. Methods The subjects were 50 Japanese first-episode untreated schizophrenia patients who met the Diagnostic and Statistical Manual of Mental Disorders Text Revision criteria and were treated with aripiprazole monotherapy. Twenty-nine were males, and 21 were females. The age ranged from 21 to 42 years (mean ± SD; 30.8 ± 5.3 years). Plasma BDNF and catecholamine metabolites were measured by ELISA and HPLC, respectively. Psychiatric symptoms were evaluated using by Positive and Negative Syndrome Scale. Results Treatment with aripiprazole for 8 weeks significantly increased plasma BDNF levels. It also changed plasma levels of homovanillic acid and 3-methoxy-4-hydroxyphenylglycol. A negative correlation was also observed between duration of psychosis and plasma BDNF levels. No correlation was observed however between plasma BDNF levels and the dose of aripiprazole. Conclusions To the best of our knowledge, this is the first report showing that aripiprazole increases plasma BDNF levels in first-episode untreated schizophrenia patients. Furthermore, the BDNF Val66Met polymorphism was independent of the response to aripiprazole. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In the present study, we investigated the serum BDNF levels and plasma IL-6 levels in patients with dysthymic disorder, major depressive disorder and control subjects. Eighteen patients who met the DSM-IV criteria (American Psychiatric Association, 1994) for dysthymic disorder (male/female: 5/13; age: 36 ± 9 year) and 20 patients (male/female: 7/13; age: 38 ± 10 year) who met the criteria for major depressive disorder were enrolled. The serum BDNF levels in patients with dysthymic and major depressive disorder were significantly lower than those in the control subjects. However, no difference was found between the dysthymic group and major depression group. The plasma IL-6 levels in the dysthymic group and major depression group were significantly higher than those in the control group. No difference was observed in the plasma IL-6 levels between the dysthymic group and major depression group. These results suggest that the pathophysiology of dysthymic disorder and major depression might be similar in terms of the blood levels of BDNF and IL-6. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]