Improvement of psychiatrists' clinical knowledge of the treatment guidelines for schizophrenia and major depressive disorders using the 'Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)' project: A nationwide dissemination, education, and evaluation study.

AIM: Although treatment guidelines for pharmacological therapy for schizophrenia and major depressive disorder have been issued by the Japanese Societies of Neuropsychopharmacology and Mood Disorders, these guidelines have not been well applied by psychiatrists throughout the nation. To address this issue, we developed the 'Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)' integrated education programs for psychiatrists to disseminate the clinical guidelines. Additionally, we conducted a systematic efficacy evaluation of the programs. METHODS: Four hundred thirteen out of 461 psychiatrists attended two 1-day educational programs based on the treatment guidelines for schizophrenia and major depressive disorder from October 2016 to March 2018. We measured the participants' clinical knowledge of the treatment guidelines using self-completed questionnaires administered before and after the program to assess the effectiveness of the programs for improving knowledge. We also examined the relation between the participants' demographics and their clinical knowledge scores. RESULTS: The clinical knowledge scores for both guidelines were significantly improved after the program. There was no correlation between clinical knowledge and participant demographics for the program on schizophrenia; however, a weak positive correlation was found between clinical knowledge and the years of professional experience for the program on major depressive disorder. CONCLUSION: Our results provide evidence that educational programs on the clinical practices recommended in guidelines for schizophrenia and major depressive disorder might effectively improve participants' clinical knowledge of the guidelines. These data are encouraging to facilitate the standardization of clinical practices for psychiatric disorders.

Remifentanil in electroconvulsive therapy: a systematic review and meta-analysis of randomized controlled trials.

In electroconvulsive therapy (ECT), remifentanil is often used concurrently with anesthetics. The objective of this study was to provide an up-to-date and comprehensive review on how the addition of remifentanil to anesthetics affects seizure duration and circulatory dynamics in mECT. We performed a meta-analysis of RCTs that investigated seizure duration and circulatory dynamics in patients treated with ECT using anesthetics alone (non-remifentanil group) and with anesthetics plus remifentanil (remifentanil group). A total of 13 RCTs (380 patients and 1024 ECT sessions) were included. The remifentanil group showed a significantly prolonged seizure duration during ECT compared to the non-remifentanil group [motor: 9 studies, SMD = 1.25, 95 % CI (0.21, 2.29), p = 0.02; electroencephalogram: 8 studies, SMD = 0.98, 95 % CI (0.14, 1.82), p = 0.02]. The maximum systolic blood pressure (SBP) was significantly reduced in the remifentanil group compared to the non-remifentanil group [7 studies, SMD = -0.36, 95 % CI (-0.65, 0.07), p = 0.02]. Substantial heterogeneity was observed for meta-analyses for seizure durations, but a pre-planned subgroup analysis revealed that seizure duration was prolonged only when the use of the anesthetic dose was reduced in the remifentanil group. The results of our study suggest that addition of remifentanil to anesthesia in ECT may lead to prolonged seizure duration when it allows the use of reduced anesthetic doses. Further, the addition of remifentanil was associated with reduced maximum SBP.

Segmentation and Volume Estimation of the Habenula Using Deep Learning in Patients With Depression.

Background: The habenula is involved in the pathophysiology of depression. However, its small structure limits the accuracy of segmentation methods, and the findings regarding its volume have been inconsistent. This study aimed to create a highly accurate habenula segmentation model using deep learning, test its generalizability to clinical magnetic resonance imaging, and examine differences between healthy participants and patients with depression. Methods: This multicenter study included 382 participants (patients with depression: N = 234, women 47.0%; healthy participants: N = 148, women 37.8%). A 3-dimensional residual U-Net was used to create a habenula segmentation model on 3T magnetic resonance images. The reproducibility and generalizability of the predictive model were tested on various validation cohorts. Thereafter, differences between the habenula volume of healthy participants and that of patients with depression were examined. Results: A Dice coefficient of 86.6% was achieved in the derivation cohort. The test-retest dataset showed a mean absolute percentage error of 6.66, indicating sufficiently high reproducibility. A Dice coefficient of >80% was achieved for datasets with different imaging conditions, such as magnetic field strengths, spatial resolutions, and imaging sequences, by adjusting the threshold. A significant negative correlation with age was observed in the general population, and this correlation was more pronounced in patients with depression (p < 10-7, r = -0.59). Habenula volume decreased with depression severity in women even when the effects of age and scanner were excluded (p = .019, η2 = 0.099). Conclusions: Habenula volume could be a pathophysiologically relevant factor and diagnostic and therapeutic marker for depression, particularly in women.

Accurate segmentation of the habenula, a brain region implicated in depression, is challenging. In this study, we developed an automated human habenula segmentation model using deep learning techniques. The model was confirmed to be reproducible and generalizable at various spatial resolutions. Application of this model to a multicenter dataset confirmed that habenula volume decreased with age in healthy volunteers, an association that was more pronounced in individuals with depression. In addition, habenula volume decreased with the severity of depression in women. This novel model for habenula segmentation enables further study of the role of the habenula in depression.

Relapse Following Electroconvulsive Therapy for Schizophrenia: A Systematic Review and Meta-analysis.

BACKGROUND: Evidence regarding schizophrenia relapse following acute electroconvulsive therapy (ECT) is sparse compared with that for depression, and we have no clear consensus on relapse proportions. We aimed to provide longitudinal information on schizophrenia relapse following acute ECT. STUDY DESIGN: This systematic review and meta-analysis included randomised controlled trials (RCTs) and observational studies on post-acute ECT relapse and rehospitalization for schizophrenia and related disorders. For the primary outcome, we calculated the post-acute ECT pooled relapse estimates at each timepoint (3, 6, 12, and 24 months post-acute ECT) using a random effects model. For subgroup analyses, we investigated post-acute ECT relapse proportions by the type of maintenance therapy. STUDY RESULTS: Among a total of 6413 records, 29 studies (3876 patients) met our inclusion criteria. The risk of bias was consistently low for all included RCTs (4 studies), although it ranged from low to high for observational studies (25 studies). Pooled estimates of relapse proportions among patients with schizophrenia responding to acute ECT were 24% (95% CI: 15-35), 37% (27-47), 41% (34-49), and 55% (40-69) at 3, 6, 12, and 24 months, respectively. When continuation/maintenance ECT was added to antipsychotics post-acute ECT, the 6-month relapse proportion was 20% (11-32). CONCLUSION: Relapse occurred mostly within 6 months post-acute ECT for schizophrenia, particularly within the first 3 months. Relapse proportions plateaued after 6 months, although more than half of all patients could be expected to relapse within 2 years. Further high-quality research is needed to optimise post-acute ECT treatment strategies in patients with schizophrenia.

Commonalities and differences in ECT-induced gray matter volume change between depression and schizophrenia.

BACKGROUND: Electroconvulsive therapy (ECT) is one of the most effective treatments for depression and schizophrenia, particularly in urgent or treatment-resistant cases. After ECT, regional gray matter volume (GMV) increases have been repeatedly reported both in depression and schizophrenia. However, the interpretation of these findings remains entangled because GMV changes do not necessarily correlate with treatment effects and may be influenced by the intervention itself. We hypothesized that the comparison of longitudinal magnetic resonance imaging data between the two diagnostic groups will provide clues to distinguish diagnosis-specific and transdiagnostic changes. METHOD: Twenty-nine Japanese participants, including 18 inpatients with major depressive disorder and 11 with schizophrenia, underwent longitudinal voxel-based morphometry before and after ECT. We investigated GMV changes common to both diagnostic groups and those specific to each group. Moreover, we also evaluated potential associations between GMV changes and clinical improvement for each group. RESULTS: In both diagnostic groups, GMV increased in widespread areas after ECT, sharing common regions including: anterior temporal cortex; medial frontal and anterior cingulate cortex; insula; and caudate nucleus. In addition, we found a schizophrenia-specific GMV increase in a region including the left pregenual anterior cingulate cortex, with volume increase significantly correlating with clinical improvement. CONCLUSIONS: Transdiagnostic volume changes may represent the effects of the intervention itself and pathophysiological changes common to both groups. Conversely, diagnosis-specific volume changes are associated with treatment effects and may represent pathophysiology-specific impacts of ECT.

Information flow and dynamic functional connectivity during electroconvulsive therapy in patients with depression.

BACKGROUND: Electroconvulsive therapy is effectively used for treatment-resistant depression; however, its neural mechanism is largely unknown. Resting-state functional magnetic resonance imaging is promising for monitoring outcomes of electroconvulsive therapy for depression. This study aimed to explore the imaging correlates of the electroconvulsive therapy effects on depression using Granger causality analysis and dynamic functional connectivity analyses. METHODS: We performed advanced analyses of resting-state functional magnetic resonance imaging data at the beginning and intermediate stages and end of the therapeutic course to identify neural markers that reflect or predict the therapeutic effects of electroconvulsive therapy on depression. RESULTS: We demonstrated that information flow between the functional networks analyzed by Granger causality changes during electroconvulsive therapy, and this change was correlated with the therapeutic outcome. Information flow and the dwell time (an index reflecting the temporal stability of functional connectivity) before electroconvulsive therapy are correlated with depressive symptoms during and after treatment. LIMITATIONS: First, the sample size was small. A larger group is needed to confirm our findings. Second, the influence of concomitant pharmacotherapy on our results was not fully addressed, although we expected it to be minimal because only minor changes in pharmacotherapy occurred during electroconvulsive therapy. Third, different scanners were used the groups, although the acquisition parameters were the same; a direct comparison between patient and healthy participant data was not possible. Thus, we presented the data of the healthy participants separately from that of the patients as a reference. CONCLUSIONS: These results show the specific properties of functional brain connectivity.

An Online Survey About Electroconvulsive Therapy in Japan During the COVID-19 Pandemic: Comparison of Early and Recent Stages.

Purpose: To provide an overview of how electroconvulsive therapy (ECT) practice in Japan has changed as the coronavirus disease 2019 (COVID-19) pandemic continues. Patients and Methods: We surveyed healthcare institutions, primarily university and general hospitals, regarding changes in the number of patients undergoing ECT and infection control measures in the early (August 2020) and recent (August 2021) stages of the COVID-19 pandemic. Data for the early and recent stages were also compared between urban and non-urban areas. Results: Among 32 facilities, the number of patients undergoing ECT decreased in 11 facilities (34.4%) from April 2020 to March 2021 compared with the previous year, whereas the number increased in 12 (37.5%) from April to June 2021 compared with the previous year. As of August 2021, some facilities had ongoing restrictions. Compared with non-urban facilities, the number of patients undergoing ECT decreased more in urban facilities, which also had more ECT restrictions. Maintenance ECT was used at the same rate as before the pandemic for 23 (82.1%) of 28 institutions. Regarding infection control measures, many facilities considered polymerase chain reaction testing before ECT and required all staff to wear surgical masks and eye shields during ECT. Conclusion: The COVID-19 pandemic in Japan greatly affected the use of ECT in 2020; however, by the summer of 2021, infection control measures were relatively well established, the number of ECT cases stabilized and increased, and the decision to use ECT was again possible.

Serial case report of high seizure threshold patients that responded to the lengthening of pulse width in ECT.

Electroconvulsive therapy (ECT) has been used as an effective treatment modality for psychiatric disorders. In patients with high seizure thresholds, augmentation strategies are considered such as changing anesthetic agents, hyperventilation, and premedication with theophylline. We tried to switch to "long (1.5 ms)" brief pulse ECT in all six patients from October 2020. The successful induction of effective seizures with "long" brief pulse stimulation in five of six patients who could not be treated adequately with standard ECT. In the current situation in cases in which brief pulse ECT, with the maximum dose did not lead to effective seizures, "long" brief pulse waves may be a promising option.

A dissemination and education programme to improve the clinical behaviours of psychiatrists in accordance with treatment guidelines for schizophrenia and major depressive disorders: the Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project.

BACKGROUND: Clinical practice guidelines for schizophrenia and major depressive disorder have been published. However, these have not had sufficient penetration in clinical settings. We developed the Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project as a dissemination and education programme for psychiatrists. AIMS: The aim of this study is to assess the effectiveness of the EGUIDE project on the subjective clinical behaviour of psychiatrists in accordance with clinical practice guidelines before and 1 and 2 years after participation in the programmes. METHOD: A total of 607 psychiatrists participated in this study during October 2016 and March 2019. They attended both 1-day educational programmes based on the clinical practice guidelines for schizophrenia and major depressive disorder, and answered web questionnaires about their clinical behaviours before and 1 and 2 years after attending the programmes. We evaluated the changes in clinical behaviours in accordance with the clinical practice guidelines between before and 2 years after the programme. RESULTS: All of the scores for clinical behaviours in accordance with clinical practice guidelines were significantly improved after 1 and 2 years compared with before attending the programmes. There were no significant changes in any of the scores between 1 and 2 years after attending. CONCLUSIONS: All clinical behaviours in accordance with clinical practice guidelines improved after attending the EGUIDE programme, and were maintained for at least 2 years. The EGUIDE project could contribute to improved guideline-based clinical behaviour among psychiatrists.

Subjective assessment of participants in education programs on clinical practice guidelines in the field of psychiatry.

The Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE) project, which is a nationwide dissemination and implementation program for clinical practice guidelines (CPGs) in the field of psychiatry, is currently ongoing. In the current study, a subjective assessment of the participants in the EGUIDE programs was assessed using a questionnaire. Then, the relationships between the subjective assessment, the characteristics of the participants, and the clinical knowledge of the CPGs were evaluated. More than 90% of the participants gave a high rating for the components of content, recommendation, knowledge, skill, and adherence, but not for the component of confidence. A positive correlation was found between years of professional experience and the score of confidence. These results suggest that it may be necessary to apply the knowledge and skills of CPGs obtained in the education programs into practice to increase confidence in the proper use of psychiatric therapies based on CPGs.

Sevoflurane in electroconvulsive therapy: A systematic review and meta-analysis of randomised trials.

Sevoflurane is the most commonly used inhaled anaesthetic in electroconvulsive therapy (ECT). The objective of this study was to provide an up-to-date and comprehensive review on how the use of sevoflurane affects seizure adequacy (seizure duration and postictal suppression index [PSI]) and circulatory dynamics in ECT. We performed a meta-analysis of RCTs that investigated seizure adequacy and circulatory dynamics in patients treated with ECT using sevoflurane (sevoflurane group) and intravenous anaesthetics (non-sevoflurane group). A total of 12 RCTs (377 patients and 1339 ECT sessions) were included. Sevoflurane significantly decreased the electroencephalogram (EEG) seizure durations in comparison with intravenous anaesthetics, whereas no significant difference was observed in PSI (EEG: 9 studies, standardized mean difference (SMD) = 0.74, 95% confidence interval (CI) = -1.11 to -0.38, p = 0.0002; PSI: 4 studies, SMD = -0.06, CI -0.13 to 0.25, p = 0.59). The use of sevoflurane in ECT significantly increased heart rate (HR) compared with intravenous anaesthetics (9 studies, SMD = 0.31, CI 012-0.51, p = 0.004). In the pre-planned subgroup analysis, sevoflurane significantly reduced seizure duration compared with other types of anaesthetics, including propofol, barbiturates and ketamine. Furthermore, it was found that the risk of adverse events in ECT with sevoflurane were not significantly different from intravenous anaesthetics (6 studies, risk ratio = 1.33, CI 0.95-1.86, p = 0.09), with agitaion being the most common adverse effects. The results of our study suggest that using sevoflurane for ECT significantly reduces seizure duration, increases maximum HR and brings about no difference in the adverse event risk compared with those using intravenous anaesthetics for ECT. Therefore, there may not be compelling evidence favouring sevoflurane use for ECT, except in cases where intravenous access is difficult.

Early and late effects of electroconvulsive therapy associated with different temporal lobe structures.

Recent studies examining electroconvulsive therapy (ECT) have reported that early sessions can induce rapid antidepressant and antipsychotic effects, and the early termination of ECT was reported to increase the risk of relapse. We hypothesized that different neural mechanisms associated with the therapeutic effects of ECT may be involved in the different responses observed during the early and late periods of ECT treatment. We investigated whether these antidepressant and antipsychotic effects were associated with temporally and spatially different regional gray matter volume (GMV) changes during ECT. Fourteen patients with major depressive disorder, with or without psychotic features, underwent 3-Tesla structural magnetic resonance imaging scans before (time point [Tp] 1), after the fifth or sixth ECT session (Tp2), and after ECT completion (Tp3). We investigated the regions in which GMV changed between Tp1 and Tp2, Tp2 and Tp3, and Tp1 and Tp3 using voxel-based morphometry. In addition, we investigated the association between regional GMV changes and improvement in depressive or psychotic symptoms. GMV increase in the left superior and inferior temporal gyrus during Tp1-Tp2 was associated with improvement in psychotic symptoms (P < 0.025). GMV increase in the left hippocampus was associated with improvement of depressive symptoms in Tp2-Tp3 (P < 0.05). Our findings suggest that different temporal lobe structures are associated with early antipsychotic and late antidepressant effects of ECT.

Prescription patterns in patients with schizophrenia in Japan: First-quality indicator data from the survey of "Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE)" project.

BACKGROUND: Guideline for Pharmacological Therapy for Schizophrenia was published by the Japanese Society of Neuropsychopharmacology in 2015. "Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE)" project aimed to standardize medical practice using quality indicators (QIs) as indices to evaluate the quality of medical practice. In this study, we have reported the quality indicator values of prescription before the beginning of the guideline lectures in the EGUIDE project to ascertain the baseline status of treating patients with schizophrenia. METHODS: A cross-sectional, retrospective case record survey was conducted, involving 1164 patients with schizophrenia at the time of discharge. We checked all types and dosage of psychotropic drugs. RESULTS: Forty-three percent of patients had antipsychotic polypharmacy, and substantial concomitant medication was observed (antidepressants; 8%, mood stabilizers: 37%, anxiolytics or hypnotics: 68%). CONCLUSIONS: In the results obtained in this study, we plant to report changes in the effectiveness of education in the EGUIDE project near the future.

Successful switch from bilateral brief pulse to right unilateral ultrabrief pulse electroconvulsive therapy after failure to induce seizures.

Inducing adequate therapeutic seizures during electroconvulsive therapy (ECT) is sometimes difficult due to a high seizure threshold, even at the maximum stimulus charge. Previous studies have demonstrated that seizure threshold is lower in patients treated with right unilateral ultrabrief pulse (RUL-UBP) ECT than in those treated with bilateral or brief pulse (BL-BP) ECT. Therefore, switching to RUL-UBP ECT may be beneficial for patients in whom seizure induction is difficult with conventional ECT. In the present report, we discuss the case of a patient suffering from catatonic schizophrenia in whom BL-BP ECT failed to induce seizures at the maximum charge. However, RUL-UBP ECT successfully elicited therapeutic seizures and enabled the patient to achieve complete remission. This case illustrates that, along with other augmentation strategies, RUL-UBP ECT represents an alternative for seizure induction in clinical practice.

Pharmacogenomic Study of Clozapine-Induced Agranulocytosis/Granulocytopenia in a Japanese Population.

BACKGROUND: Clozapine-induced agranulocytosis (CIA)/clozapine-induced granulocytopenia (CIG) (CIAG) is a life-threatening event for schizophrenic subjects treated with clozapine. METHODS: To examine the genetic factor for CIAG, a genome-wide pharmacogenomic analysis was conducted using 50 subjects with CIAG and 2905 control subjects. RESULTS: We identified a significant association in the human leukocyte antigen (HLA) region (rs1800625, p = 3.46 × 10(-9), odds ratio [OR] = 3.8); therefore, subsequent HLA typing was performed. We detected a significant association of HLA-B*59:01 with CIAG (p = 3.81 × 10(-8), OR = 10.7) and confirmed this association by comparing with an independent clozapine-tolerant control group (n = 380, p = 2.97 × 10(-5), OR = 6.3). As we observed that the OR of CIA (OR: 9.3~15.8) was approximately double that in CIG (OR: 4.4~7.4), we hypothesized that the CIG subjects were a mixed population of those who potentially would develop CIA and those who would not develop CIA (non-CIA). This hypothesis allowed the proportion of the CIG who were non-CIA to be calculated, enabling us to estimate the positive predictive value of the nonrisk allele on non-CIA in CIG subjects. Assuming this model, we estimated that 1) ~50% of CIG subjects would be non-CIA; and 2) ~60% of the CIG subjects without the risk allele would be non-CIA and therefore not expected to develop CIA. CONCLUSIONS: Our results suggest that HLA-B*59:01 is a risk factor for CIAG in the Japanese population. Furthermore, if our model is true, the results suggest that rechallenging certain CIG subjects with clozapine may not be always contraindicated.

Elongation of pulse width as an augmentation strategy in electroconvulsive therapy.

Inducing adequate therapeutic seizures during electroconvulsive therapy is sometimes difficult, even at the maximum stimulus charge, due to a high seizure threshold. Here, we describe two patients with very poor seizure responses at the maximum charge using conventional stimulus parameters in whom responses were successfully augmented by widening the pulse width at the same or even lower stimulus charge. This strategy could be an additional option for seizure augmentation in clinical practice. The potential clinical utility of stimulus parameter modifications should be further investigated.

Corticolimbic balance shift of regional glucose metabolism in depressed patients treated with ECT.

BACKGROUND: Although the clinical efficacy of electroconvulsive therapy (ECT) has been well established in patients with pharmacotherapy-resistant depression, the physiological mechanism and changes in regional cerebral function after ECT are unclear. METHODS: We recruited 16 depressed patients who underwent ECT, and 11 healthy controls. The change in cerebral glucose metabolism was evaluated before and after a series of ECT using [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET). RESULTS: Before ECT, the patient group showed significant hypometabolism in the superior frontal gyrus, and hypermetabolism in the inferior temporal gyri compared with healthy controls, and these abnormalities remained after ECT. Comparisons between pre- and post-ECT metabolic activity revealed decreased regional metabolism in the frontotemporal neocortical areas after ECT, while increased metabolism was found in the right medial temporal structures including amygdala and pons. In addition, a decrease in glucose metabolism in the fronto-temporo-parietal regions correlated with an increase in glucose metabolism in the right medial temporal regions across subjects. LIMITATIONS: There was considerable variability in the interval between the last ECT and FDG-PET scan. Depressed subjects were maintained on medication. The subjects included both major depressive disorder and bipolar disorder patients, as well as both ECT responders and non-responders. CONCLUSION: Depression refractory to pharmacotherapy might have functional deficits in specific circumscribed frontal and temporal structures. ECT resolves the clinical symptoms without largely affecting these brain metabolic abnormalities. In contrast, ECT shifts the balance of corticolimbic function, which might explain how ECT ameliorates symptoms of depression in patients.

Insomnia and depression during protective isolation in patients with hematological disorders.

OBJECTIVE: Patients treated in a protective isolation unit (PIU) often experience loneliness and increased feelings of seclusion, leading to elevated levels of distress, but the relationship between psychiatric distress and environmental factors is unclear. Therefore, we retrospectively compared the impact of environmental factors on insomnia and depression between patients in the PIU and those in a standard ward (SW). METHODS: Subjects were 246 patients with hematological disorders hospitalized in Meitetsu Hospital between April 1, 2007 and July 31, 2008 (62 PIU patients and 184 SW patients). We assessed insomnia and depression, as well as concomitant corticosteroid (CS) administration, stem cell transplantation (SCT) therapy, and complications resulting from these therapies. Details of medical history and patient information were retrospectively extracted from patients' charts, medical records and the electronic laboratory database at the hospital. RESULTS: Patients in the PIU tended to be complicated by insomnia or depression more than those in the SW, but the stay in the PIU was not significantly related to the incidence of insomnia or depression. Our findings indicated that use of CS was a risk factor for insomnia. The prevalence of depression was higher in patients with therapeutic complications. All PIU patients with depression also received SCT. CONCLUSION: Our findings suggest an increased potential for insomnia after administration of CS and depression in cases with complications after SCT, which is important to keep in mind for patients with hematological disorders.