Factors associated with hypnotics polypharmacy in the Japanese population.

OBJECTIVE: Insomnia disorder is a global public health issue, commonly treated with hypnotics. However, long-term use of benzodiazepine derivatives (BZDs), especially polypharmacy with this kind of drug, carries risks for dependence and abuse. This study using large-scale medical insurance records investigated the causes of polypharmacy through the treatment of insomnia disorder. METHODS: A cross-sectional study analyzed anonymized medical record data from July 2014 to March 2018 provided by a nationwide Japanese health insurance association covering 405,952 individuals. Outpatients prescribed at least one sleep medication were included. Demographic data, pharmacological classification of the drugs, and comorbidities were assessed using hierarchical logistic regression analysis to explore their associations with polypharmacy. RESULTS: Of the 33,212 outpatients who were prescribed sleep medications, 32.5 % were prescribed multiple types. After adjusting for demographics and type of sleep medications as covariates, hypnotic polypharmacy was significantly associated with younger age, the presence of certain kinds of comorbidities, and using BZD anxiolytics before bedtime with the highest adjusted odds ratios (8.01-9.39) when referenced with BZD hypnotics. On the other hand, usage of orexin receptor antagonists, melatonin receptor agonists, and Z-drugs indicated lower odds ratios (0.74-0.87). CONCLUSIONS: Hypnotic polypharmacy is relatively common in the Japanese general population. With the introduction of non-pharmacological therapy in mind, assessing patients' comorbidities and avoiding the use of benzodiazepines, especially BZD anxiolytics, before bedtime would be recommended to prevent polypharmacy.

Human-Comparable Sensitivity of Large Language Models in Identifying Eligible Studies Through Title and Abstract Screening: 3-Layer Strategy Using GPT-3.5 and GPT-4 for Systematic Reviews.

BACKGROUND: The screening process for systematic reviews is resource-intensive. Although previous machine learning solutions have reported reductions in workload, they risked excluding relevant papers. OBJECTIVE: We evaluated the performance of a 3-layer screening method using GPT-3.5 and GPT-4 to streamline the title and abstract-screening process for systematic reviews. Our goal is to develop a screening method that maximizes sensitivity for identifying relevant records. METHODS: We conducted screenings on 2 of our previous systematic reviews related to the treatment of bipolar disorder, with 1381 records from the first review and 3146 from the second. Screenings were conducted using GPT-3.5 (gpt-3.5-turbo-0125) and GPT-4 (gpt-4-0125-preview) across three layers: (1) research design, (2) target patients, and (3) interventions and controls. The 3-layer screening was conducted using prompts tailored to each study. During this process, information extraction according to each study's inclusion criteria and optimization for screening were carried out using a GPT-4-based flow without manual adjustments. Records were evaluated at each layer, and those meeting the inclusion criteria at all layers were subsequently judged as included. RESULTS: On each layer, both GPT-3.5 and GPT-4 were able to process about 110 records per minute, and the total time required for screening the first and second studies was approximately 1 hour and 2 hours, respectively. In the first study, the sensitivities/specificities of the GPT-3.5 and GPT-4 were 0.900/0.709 and 0.806/0.996, respectively. Both screenings by GPT-3.5 and GPT-4 judged all 6 records used for the meta-analysis as included. In the second study, the sensitivities/specificities of the GPT-3.5 and GPT-4 were 0.958/0.116 and 0.875/0.855, respectively. The sensitivities for the relevant records align with those of human evaluators: 0.867-1.000 for the first study and 0.776-0.979 for the second study. Both screenings by GPT-3.5 and GPT-4 judged all 9 records used for the meta-analysis as included. After accounting for justifiably excluded records by GPT-4, the sensitivities/specificities of the GPT-4 screening were 0.962/0.996 in the first study and 0.943/0.855 in the second study. Further investigation indicated that the cases incorrectly excluded by GPT-3.5 were due to a lack of domain knowledge, while the cases incorrectly excluded by GPT-4 were due to misinterpretations of the inclusion criteria. CONCLUSIONS: Our 3-layer screening method with GPT-4 demonstrated acceptable level of sensitivity and specificity that supports its practical application in systematic review screenings. Future research should aim to generalize this approach and explore its effectiveness in diverse settings, both medical and nonmedical, to fully establish its use and operational feasibility.

Practice Guidelines for Bipolar Disorder by the JSMD (Japanese Society of Mood Disorders).

The Japanese Society of Mood Disorders (JSMD) published treatment guidelines of bipolar disorder in 2011. The present guidelines incorporating new findings were developed to comply to the guidelines of the National Academy of Medicine (NAM) by utilizing systematic reviews and meta-analysis and taking patient and family opinions as well as insights from multiple professional fields into account. They support combination therapy using mood stabilizers and second-generation antipsychotics in many aspects. They also have limitations, including the grouping of mood stabilizers and second-generation antipsychotics when meta-analysis was performed despite their distinct properties, due to the scarcity of drug-specific evidence. Despite the limitations, these guidelines provide clinical decision support for psychiatrists in Japan.

Successful treatment with guanfacine in a long-COVID case manifesting marked cognitive impairment.

BACKGROUND: Persistent cognitive impairment is a serious consequence of the post-COVID condition. However, there have been no established effective treatments for this pathophysiology supported by sufficient evidence. CASE PRESENTATION: A 32-year-old woman became aware of difficulty in word recalling, reading, and writing as well as difficulty in completing various household multitasks 3 weeks after the COVID-19 infection. Although blood tests, magnetic resonance imaging, electroencephalography, and Kohs block design test were all within normal limits, completion time by trail making test (TMT) A or B was markedly delayed. Finally, she was referred to our hospital 3 months after the infection. At baseline, the THINC integrated tool (THINC-it), a digital battery consisting of the five-item version of the perceived deficit questionnaire (PDQ-5), choice reaction time (CRT), 1-back test, digit symbol substitution test (DSST), and TMT-B, revealed poor capability in attention, working memory, and executive function. Also, near-infrared spectroscopy (NIRS) demonstrated no activation in frontal or temporal regions during verbal fluency task. Extended-release guanfacine (GXR) 2 mg/day was initiated and a month later was elevated up to 4 mg/day as a maintenance dose. The PDQ-5, CRT, 1-back test, DSST, and TMT-B were dramatically improved 1 month after GXR treatment. NIRS finding was also normalized after 2 months of treatment. These effects were successfully maintained throughout the 6-month follow-up period. CONCLUSION: GXR may be helpful in improving subjective/objective cognitive functioning and frontotemporal brain activity in long-COVID patients manifesting apparent cognitive impairment.

Treatment strategies for insomnia in Japanese primary care physicians' practice: A Web-based questionnaire survey.

BACKGROUND: It is unclear how primary care physicians manage insomnia after the introduction of novel hypnotics such as orexin receptor antagonists and melatonin receptor agonists. This Web-based questionnaire survey aimed to examine treatment strategies for insomnia in Japanese primary care practice. METHODS: One-hundred-and-seventeen primary care physicians were surveyed on the familiarity of each management option for insomnia on a binary response scale (0 = "unfamiliar"; 1 = "familiar") and how they managed insomnia using a nine-point Likert scale (1 = "I never prescribe/perform it"; 9 = "I often prescribe/perform it"). Physicians who were unfamiliar with a management option were deemed to have never prescribed or performed it. RESULTS: Regarding medication, most physicians were familiar with novel hypnotics. Suvorexant was the most used hypnotic, followed by lemborexant and ramelteon. These novel hypnotics averaged 4.8-5.4 points and 4.0-4.7 points for sleep onset and sleep maintenance insomnia, respectively. By contrast, most benzodiazepines were seldom used below two points. Regarding psychotherapy, only approximately 40% of the physicians were familiar with cognitive behavioral therapy for insomnia (CBT-I) and they rarely implemented it, at an average of 1.5-1.6 points. More physicians were familiar with single-component psychotherapies (i.e., relaxation, sleep restriction therapy, and stimulus control) compared to CBT-I, and 48-74% of them implemented it slightly more often, with scores ranging from 2.6 to 3.4 points. CONCLUSION: This study suggests that Japanese primary care physicians seldom use CBT-I to treat insomnia. In addition, they use novel sleep medications more frequently than benzodiazepines in terms of pharmacotherapy. The use and availability of CBT-I in Japanese primary care might be facilitated by: educating primary care physicians, implementing brief or digital CBT-I, and/or developing collaborations between primary care physicians and CBT-I specialists.

A psychometric analysis of the Japanese version of the clinically useful depression outcome scale supplemented with questions for the DSM-5 anxious distress specifier (CUDOS-A).

AIM: The aim of the study was to identify the clinical significance of anxiety in those with depression, the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) defined criteria for an anxious distress specifier for major depressive disorder (MDD). The Clinically Useful Depression Outcome Scale (CUDOS) supplemented with questions for the DSM-5 anxious distress specifier (CUDOS-A) is a self-report instrument to assess the clinical significance of anxiety in addition to assess symptoms and the severity of depression. This study aimed to evaluate the psychometric properties of the Japanese version of the CUDOS-A. METHODS: An observational, prospective study was conducted with 131 MDD outpatients and 200 healthy controls. The Japanese version of the CUDOS-A, along with other measures, was administered to assess depressive symptoms, anxiety, social function, and biological rhythm. Reliability and validity analyses were performed, including internal consistency, test-retest reliability, convergent validity, and contrasted-groups validity. RESULTS: The Japanese version of the CUDOS-A demonstrated excellent internal consistency (Cronbach's alpha = 0.96) and test-retest reliability (ICC = 0.78). Significant positive correlations were found between the CUDOS-A and measures of depression, anxiety, social function, and biological rhythm (all, p < 0.001), supporting its convergent validity. The CUDOS-A effectively differentiated between patients with MDD and healthy controls (p < 0.001), indicating good contrasted-groups validity. CONCLUSIONS: The Japanese version of the CUDOS-A is a useful measure for research and for clinical practice, enabling the efficient assessment of anxious distress in individuals with depression.

Cluster analysis of patients with alcohol use disorder featuring alexithymia, depression, and diverse drinking behavior.

AIM: This study aimed to identify subgroups of alcohol use disorder (AUD) based on a multidimensional combination of alexithymia, depression, and diverse drinking behavior. METHOD: We recruited 176 patients with AUD, which were initially divided into non-alexithymic (n = 130) and alexithymic (n = 46) groups using a cutoff score of 61 on the Toronto Alexithymia Scale (TAS-20). Subsequently, the profiles of the two groups were compared. Thereafter, a two-stage cluster analysis using hierarchical and K-means methods was performed with the Z-scores from the TAS-20, the Quick Inventory of Depressive Symptomatology Self-Report Japanese Version, the 12-item questionnaire for quantitative assessment of depressive mixed state, and the 20-item questionnaire for drinking behavior pattern. RESULTS: In the first analysis, Alexithymic patients with AUD showed greater depressive symptoms and more pathological drinking behavior patterns than those without alexithymia. Cluster analysis featuring alexithymia, depression, and drinking behavior identified three subtypes: Cluster 1 (core AUD type) manifesting pathological drinking behavior highlighting automaticity; Cluster 2 (late-onset type) showing relatively late-onset alcohol use and fewer depressive symptoms or pathological drinking behavior; and Cluster 3 (alexithymic type) characterized by alexithymia, depression, and pathological drinking behavior featuring greater coping with negative affect. CONCLUSION: The multidimensional model with alexithymia, depression, and diverse drinking behavior provided possible practical classification of AUD. The alexithymic subtype may require more caution, and additional support for negative affect may be necessary due to accompanying mood problems and various maladaptive drinking behaviors.

The effect of education regarding treatment guidelines for schizophrenia and major depressive disorders on psychiatrists' hypnotic medication prescribing behavior: a multicenter study.

BACKGROUND: To examine whether the "Effectiveness of Guideline for Dissemination and Education in psychiatric treatment (EGIUDE)" project affects the rate of prescriptions of hypnotic medication and the type of hypnotic medications prescribed among psychiatrists, for schizophrenia and major depressive disorder in Japan. METHODS: The EGUIDE project is a nationwide prospective study of evidence-based clinical guidelines for schizophrenia and major depressive disorder in Japan. From 2016 to 2021, clinical and prescribing data from patients discharged from hospitals participating in the EGUIDE project were used to examine hypnotic medication prescriptions The prescribing rate of hypnotics and the prescribing rate of each type of hypnotic (benzodiazepine receptor agonist, nonbenzodiazepine receptor agonist, melatonin receptor agonist, and orexin receptor antagonist) were compared among patients who had been prescribed medication by psychiatrists participating in the EGUIDE project and patients who had been prescribed medication by nonparticipating psychiatrists. Multivariate logistic regression analysis was performed to examine the effect of the EGUIDE project on the prescription of hypnotic medications. RESULTS: A total of 12,161 patients with schizophrenia and 6,167 patients with major depressive disorder were included. Psychiatrists participating in the EGUIDE project significantly reduced the rate of prescribing hypnotic medication and benzodiazepine receptor agonists for both schizophrenia (P < 0.001) and major depressive disorder (P < 0.001) patients. CONCLUSION: This is the first study to investigate the educational effects of guidelines for the treatment of psychiatric disorders on psychiatrists in terms of prescribing hypnotic medications to patients. The EGUIDE project may play an important role in reducing hypnotic medication prescription rates, particularly with respect to benzodiazepine receptor agonists. The results suggest that the EGUIDE project may result in improved therapeutic behavior.

Profiles and the impact of affective temperaments on alcohol use disorder: a cross-sectional study.

AIMS: This study aimed to explore the profiles and impact of affective temperaments, together with social and clinical backgrounds, including affective symptoms, in patients with alcohol use disorder (AUD). METHODS: This study included 314 low-risk drinkers and 257 patients with AUD. To assess affective temperament, we used the short version of the temperament evaluation of Memphis, Pisa, Paris, and San Diego. To evaluate depressive and mixed symptoms, the quick inventory of depressive symptomatology self-report Japanese version and 12-item questionnaire for the quantitative assessment of the depressive mixed state were used. We compared the profiles of affective temperaments as well as social and clinical backgrounds, including affective symptoms, between the two groups and further performed logistic regression analyses to explore the factors contributing to AUD. RESULTS: Our analysis showed higher cyclothymic, hyperthymic, and irritable temperament scores and lower depressive temperament scores in patients with AUD than that in nonclinical drinkers. Regarding other social and clinical backgrounds, patients with AUD were less educated and employed and more experienced depressive and mixed symptoms. Logistic regression analysis identified hyperthymic temperament as a positive contributor and depressive temperament as a negative contributor to AUD. CONCLUSIONS: Our findings indicated potential bipolarity in patients with AUD, as manifested by a more hyperthymic temperament in contrast to less depressive temperament. Despite their self-perceived adaptive temperament profiles, patients showed poorer social outcomes and more affective symptoms. This gap may be partly explained by a lack of insight unique to AUD psychology, which potentially disturbs problem recognition.

Assessing the Quick Inventory of Depressive Symptomatology Self-Report scores to predict continuous employment in mood disorder patients.

Objective: Depression significantly impacts the job performance and attendance of workers, leading to increased absenteeism. Predicting occupational engagement for individuals with depression is of paramount importance. This study aims to determine the cut-off score which predicts continuous employment for patients with mood disorders using the Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR). Methods: In a prospective observational trial conducted in Tokyo, 111 outpatients diagnosed with either major depressive disorder or bipolar depression were enrolled. Their employment statuses of these participants were tracked over a six-month period after their QIDS-SR scores were recorded. Based on their employment trajectories, participants were categorized into either continuous or non-continuous employment groups. Binary logistic regression was applied to examine the relationship between the QIDS-SR scores and employment outcomes, with adjustments for age, gender, and psychiatric diagnoses. Receiver operating characteristic curves were utilized to identify the optimal QIDS-SR cut-off values for predicting continuous employment. Findings: Binary logistic regression demonstrated that a lower score on the QIDS-SR was linked to an elevated likelihood of continuous employment (adjusted odds ratio 1.15, 95% CI: 1.06-1.26, p=0.001). The optimal cut-off point, determined by the Youden Index, was 10/11, showcasing a 63% sensitivity and 71% specificity. Conclusion: The results emphasize the potential of the QIDS-SR as a prognostic instrument for predicting employment outcomes among individuals with depressive disorders. These findings further underscore the importance of managing depressive symptoms to mild or lower intensities to ensure ongoing employment.

Drinking behavior patterns may be associated with persistent depressive symptoms after alcohol abstinence in alcohol use disorder.

AIM: This study examined the association between drinking behavior patterns and depressive symptoms after alcohol abstinence in patients with alcohol use disorder (AUD). METHOD: We recruited 102 AUD inpatients with baseline depressive symptoms, indicated by scores ≥6 on the Quick Inventory of Depressive Symptomatology Self-Report Japanese Version (QIDS-SR-J) pre-detoxification. Post-4-week abstinence, remission was defined as QIDS-SR-J scores <6. Patients were classified into remitted (n = 51) and persistent (n = 51) groups. Comparative analyses were conducted using patient profiles and the Drinking Behavior Pattern 20-item Questionnaire (DBP-20). Logistic regression identified factors related to post-abstinence persistent depression. Receiver operating characteristic curve analysis determined DBP-20 cutoff scores differentiating between persistent and remitted depression. RESULTS: The persistent group exhibited higher scores in the DBP-20 "coping with negative affect" subscale. Logistic regression showed low education, unemployment, and using alcohol for coping as significant factors for persistent depression. Conversely, an automatic drinking pattern indicated natural remission post-abstinence. A subscale score of ≥8 in alcohol use for coping, especially among unemployed patients, predicted persistent depression (sensitivity 86.8%, positive predictive value 73.3%). CONCLUSION: Unemployed patients with AUD using alcohol to cope with negative affect may experience residual depression even after detoxification. In contrast, patients with AUD with predominantly automatic drinking behavior may exhibit natural remission post-abstinence.

Prevalence of somatic diseases in adults with attention deficit hyperactivity disorder in Japan is highest in people aged ≥40 years with mental disorders: a cross-sectional study of a Japanese health insurance claims database.

Introduction: Studies have reported an association between attention deficit hyperactivity disorder (ADHD) and somatic diseases; however, the correlation of mental disorders with the association between ADHD and somatic diseases remains uninvestigated. This study investigated and compared the prevalence of somatic diseases among adults with/without ADHD, stratified by the presence or absence of mental disorders. Methods: This cross-sectional study (October 2020-September 2021), using data (June 2013-September 2021) from a Japanese health insurance claims database, included adult participants with a medical record of and receiving medication for ADHD (ADHD group); the control group (matched 1:5 by age/sex) comprised participants without ADHD. The prevalence and odds ratio (OR; ADHD versus control) of type 2 diabetes mellitus (T2DM), diabetes complications, hypertension, cardiovascular disease (CVD), dyslipidemia, gout and hyperuricemia, chronic obstructive pulmonary disease (COPD), non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH), and atopic dermatitis were investigated. Pooled ORs for stratified analysis were calculated using the Mantel-Haenszel method. Results: In the matched analysis sets, the ORs for all somatic diseases were significantly higher for the ADHD group (n=15,028) versus the control group (n=74,796). On stratified analysis, the Mantel-Haenszel ORs were significant for NAFLD/NASH (1.53; 95% confidence interval [CI]: 1.34, 1.73), diabetes complications (1.39; 95% CI: 1.09, 1.77), and gout and hyperuricemia (1.34; 95% CI: 1.19, 1.51). Furthermore, the stratum-specific ORs for T2DM, hypertension, and dyslipidemia were >1 and <1 in the presence and absence of mental disorders, respectively. The prevalence of all somatic diseases except atopic dermatitis increased with age. For participants aged ≥40 years, the Mantel-Haenszel ORs were significant for all somatic diseases except CVD, COPD, and atopic dermatitis. Conclusions: The prevalence of several somatic diseases, including chronic disorders, was high among adults with ADHD, particularly in those aged ≥40 years and those with mental disorders.

Associations between relapse and drinking behaviors in patients with alcohol use disorders: A 6-month prospective study.

BACKGROUND: Habitual behaviors, rather than goal-oriented behaviors, mainly characterize drinking patterns in patients with alcohol use disorder (AUD). However, few studies have focused on the influence of drinking behavior on AUD relapse. This prospective study examined associations between drinking behavior patterns and alcohol-use relapse using the 20-item questionnaire for drinking behavior patterns (DBP-20). METHODS: We enrolled patients with AUD and compared the cohort's demographic data and 6-month outcomes based on the DBP-20 and the Alcohol Use Disorders Identification Test between two groups (alcohol use relapse vs. abstinence). We also assessed the results for significant factors related to relapse. RESULTS: We included 105 patients with AUD. More patients in the relapse group (n = 63) were active smokers and lived alone, while fewer took medication with cyanamide or disulfiram than those in the abstinence group (n = 42). The DBP-20 automaticity subscale score was higher in the relapse group than that in the abstinence group. Current smoker, living alone, and automatic drinking habits were significantly associated with AUD relapse. CONCLUSIONS: Automaticity may be a risky drinking behavior that leads to future relapse in patients with AUD, justifying behavioral strategies to combat automatic drinking for relapse prevention.

Age-related cognitive decline is accelerated in alcohol use disorder.

This study aimed to examine potential cognitive impairments in patients with alcohol use disorder (AUD), and explore the factors affecting them. We recruited 97 inpatients with AUD, showing superficially normal cognitive function (mini-mental state examination score ≥24) for this study. We assessed cognitive function after a 4-week post-abstinence period using the Brief Assessment of Cognition in Schizophrenia-Japanese version (BACS-J). Relationships between BACS-J subcategory/composite raw scores and Z-scores (deviation from standard data in healthy Japanese) and background factors such as age, sex, education, smoking status, mini-mental state examination score, body mass index, systolic blood pressure, severity of depression, alcohol consumption, and laboratory findings were analyzed. Multiple regression analysis showed that the age (p < 0.001) and total bilirubin level (p = 0.014) were worsening factors for the BACS-J composite raw score, whereas education (p < 0.001) was a protective factor. An inverse correlation was apparent between the age and the composite Z-score of the BACS-J (r = -0.431, p < 0.001). Receiver operating characteristic (ROC) analysis identified 53 years as the cutoff age for predicting more than -2SD cognitive decline from the normal standard, with a high negative predictive value (95%). Patients with AUD aged ≥53 years showed more pronounced impairments in verbal memory, working memory, verbal fluency, and attention than those younger than 53 years (p < 0.05). These findings clearly demonstrate accelerated age-related cognitive decline in patients with AUD, especially those aged ≥53 years, suggesting the necessity of early intervention in patients with AUD to prevent progressive cognitive impairment and preserve their quality of life.

Elevated Brain-Derived Neurotrophic Factor Levels During Depressive Mixed States.

OBJECTIVE: Neurotrophin-like brain-derived neurotrophic factor (BDNF) and pro-inflammatory cytokines may modulate the pathophysiology of mood disorders. Although several studies show alterations in these biomarkers during the depressive, manic, and euthymic states of mood disorders, evidence is lacking for those in a mixed state. Therefore, this study aimed to investigate the relationship between the depressive mixed state (DMX) and peripheral neurobiological factors. METHODS: We enrolled 136 patients with major depressive episodes. Depressive symptoms were assessed using the Quick Inventory of Depressive Symptomatology Self-Report Japanese version (QIDS-SR-J). The severity of DMX was assessed using the self-administered 12-item questionnaire (DMX-12). Categorical screening as DMX-positive (n=54) was determined by a cutoff score of 13 or more in the specific eight symptoms from the DMX-12; the remaining were DMX-negative (n=82). Serum BDNF, tumor necrosis factor-α, highsensitivity C-reactive protein, and interleukin-6 levels were measured. RESULTS: When comparing biomarkers between the DMX-positive and DMX-negative groups, higher serum BDNF concentration in the DMX-positive group than in the DMX-negative group was the only significant finding (p=0.009). A positive correlation existed between the total score of the eight specific symptoms of DMX-12 and the BDNF concentration (r=0.190, p=0.027). After adjustment for confounders, logistic regression analysis revealed that BDNF (odds ratio [OR]=1.07, 95% confidence interval [CI]=1.00-1.14, p=0.045), bipolar diagnosis (OR=3.43, 95% CI=1.36-8.66, p=0.009), and total QIDS-SR-J score (OR=1.29, 95% CI=1.15-1.43, p<0.001) were significantly associated with DMX positivity. CONCLUSION: BDNF was positively associated with DMX severity, suggesting that higher BDNF concentrations may be involved in the pathophysiology of DMX.

Effect of education regarding treatment guidelines for schizophrenia and depression on the treatment behavior of psychiatrists: A multicenter study.

AIM: This study aims to examine the real-world effectiveness of education regarding clinical guidelines for psychiatric disorders using 'the Effectiveness of guidelines for dissemination and education in psychiatric treatment (EGUIDE)' project. METHODS: The EGUIDE project is a nationwide prospective implementation study of two clinical practice guidelines, i.e., the Guideline for Pharmacological Therapy of Schizophrenia and the Treatment Guidelines for Major Depressive Disorders, in Japan. Between 2016 and 2019, 782 psychiatrists belonging to 176 hospitals with psychiatric wards participated in the project and attended lectures on clinical practice guidelines. The proportions of guideline-recommended treatments in 7405 patients with schizophrenia and 3794 patients with major depressive disorder at participating hospitals were compared between patients under the care of psychiatrists participating in the project and those not participating in the project. Clinical and prescribing data on the patients discharged from April to September each year from participating hospitals of the project were also analyzed. RESULTS: The proportions of three quality indicators (antipsychotic monotherapy regardless of whether other psychotropics medication, antipsychotic monotherapy without other psychotropics and no prescription of anxiolytics or hypnotics) for schizophrenia were higher among participating psychiatrists than among nonparticipating psychiatrists. As similar results were obtained in major depressive disorder, the effectiveness of the project for the dissemination of guideline-recommended treatment has been replicated. CONCLUSION: This strategy of providing education regarding the clinical guidelines for psychiatric disorders was effective in improving the treatment-related behavior of psychiatrists. The use of this education-based strategy might contribute to resolving the mental health treatment gap.

Development and acceptability testing of a decision aid for considering whether to reduce antipsychotics in individuals with stable schizophrenia.

AIM: Continued antipsychotic treatment is the key to preventing relapse. Maintenance antipsychotic monotherapy and optimal dose use are recommended for individuals with stable schizophrenia because of their undesirable effects. Decision aids (DAs) are clinical conversation tools that facilitate shared decision-making (SDM) between patients and health-care providers. This study aimed to describe the development process and results of acceptability testing of a DA for individuals with stable schizophrenia, considering (i) whether to continue high-dose antipsychotics or reduce to the standard dose and (ii) whether to continue two antipsychotics or shift to monotherapy. METHODS: A DA was developed according to the guidelines for the appropriate use of psychotropic medications and International Patient Decision Aid Standards (IPDAS). First, a DA prototype was developed based on a previous systematic review and meta-analysis conducted for identifying the effects of continuing or reducing antipsychotic treatment. Second, mixed-method survey was performed among individuals with schizophrenia and health-care providers to modify and finalize the DA. RESULTS: The DA consisted of an explanation of schizophrenia, options to continue high-dose antipsychotics or reduce to the standard dose, options to continue two antipsychotics or shift to monotherapy, pros and cons of each option, and a value-clarification worksheet for each option. The patients (n = 20) reported acceptable language use (75%), adequate information (75%), and well-balanced presentation (79%). Health-care providers (n = 20) also provided favorable overall feedback. The final DA covered six IPDAS qualifying criteria. CONCLUSION: A DA was successfully developed for schizophrenia, considering whether to reduce antipsychotics, which can be used in the SDM process.

Delayed sleep-wake phase disorder and its related sleep behaviors in the young generation.

Delayed sleep-wake phase disorder (DSWPD) is a sleep disorder in which the habitual sleep-wake timing is delayed, resulting in difficulty in falling asleep and waking up at the desired time. Patients with DSWPD frequently experience fatigue, impaired concentration, sleep deprivation during weekdays, and problems of absenteeism, which may be further complicated by depressive symptoms. DSWPD is typically prevalent during adolescence and young adulthood. Although there are no studies comparing internationally, the prevalence of DSWPD is estimated to be approximately 3% with little racial differences between Caucasians and Asians. The presence of this disorder is associated with various physiological, genetic and psychological as well as behavioral factors. Furthermore, social factors are also involved in the mechanism of DSWPD. Recently, delayed sleep phase and prolonged sleep duration in the young generation have been reported during the period of COVID-19 pandemic-related behavioral restrictions. This phenomenon raises a concern about the risk of a mismatch between their sleep-wake phase and social life that may lead to the development of DSWPD after the removal of these restrictions. Although the typical feature of DSWPD is a delay in circadian rhythms, individuals with DSWPD without having misalignment of objectively measured circadian rhythm markers account for approximately 40% of the cases, wherein the psychological and behavioral characteristics of young people, such as truancy and academic or social troubles, are largely involved in the mechanism of this disorder. Recent studies have shown that DSWPD is frequently comorbid with psychiatric disorders, particularly mood and neurodevelopmental disorders, both of which have a bidirectional association with the pathophysiology of DSWPD. Additionally, patients with DSWPD have a strong tendency toward neuroticism and anxiety, which may result in the aggravation of insomnia symptoms. Therefore, future studies should address the effectiveness of cognitive-behavioral approaches in addition to chronobiological approaches in the treatment of DSWPD.

Development and acceptability of a decision aid for anxiety disorder considering discontinuation of benzodiazepine anxiolytic.

Aim: We aimed to develop a decision aid (DA) for individuals with anxiety disorders who consider tapering benzodiazepine (BZD) anxiolytics, and if tapering, tapering BZD anxiolytics with or without cognitive behavioral therapy (CBT) for anxiety. We also assessed its acceptability among stakeholders. Methods: First, we conducted a literature review regarding anxiety disorders to determine treatment options. We cited the results of the systematic review and meta-analysis, which we conducted previously, to describe the related outcomes of two options: tapering BZD anxiolytics with CBT and tapering BZD anxiolytics without CBT. Second, we developed a DA prototype in accordance with the International Patient Decision Aid Standards. We carried out a mixed methods survey to assess the acceptability among stakeholders including those with anxiety disorders and healthcare providers. Results: Our DA provided information such as explanation of anxiety disorders, options of tapering or not tapering BZD anxiolytics (if tapering, the options of tapering BZD anxiolytics with or without CBT) for anxiety disorder, benefits and risks of each option, and a worksheet for value clarification. For patients (n = 21), the DA appeared to be acceptable language (86%), adequate information (81%), and well-balanced presentation (86%). The developed DA was also acceptable for healthcare providers (n = 10). Conclusion: We successfully created a DA for individuals with anxiety disorders who consider tapering BZD anxiolytics, which was acceptable for both patients and healthcare providers. Our DA was designed to assist patients and healthcare providers to involve decision-making about whether to taper BZD anxiolytics or not.

Treatment strategy for insomnia disorder: Japanese expert consensus.

Purpose: There is a lack of evidence regarding answers for clinical questions about treating insomnia disorder. This study aimed to answer the following clinical questions: (1) how to use each hypnotic and non-pharmacological treatment differently depending on clinical situations and (2) how to reduce or stop benzodiazepine hypnotics using alternative pharmacological and non-pharmacological treatments. Methods: Experts were asked to evaluate treatment choices based on 10 clinical questions about insomnia disorder using a nine-point Likert scale (1 = "disagree" to 9 = "agree"). The responses of 196 experts were collected, and the answers were categorized into first-, second-, and third-line recommendations. Results: The primary pharmacological treatment, lemborexant (7.3 ± 2.0), was categorized as a first-line recommendation for sleep initiation insomnia, and lemborexant (7.3 ± 1.8) and suvorexant (6.8 ± 1.8) were categorized as the first-line recommendations for sleep maintenance insomnia. Regarding non-pharmacological treatments for primary treatment, sleep hygiene education was categorized as the first-line recommendation for both sleep initiation (8.4 ± 1.1) and maintenance insomnia (8.1 ± 1.5), while multicomponent cognitive behavioral therapy for insomnia was categorized as the second-line treatment for both sleep initiation (5.6 ± 2.3) and maintenance insomnia (5.7 ± 2.4). When reducing or discontinuing benzodiazepine hypnotics by switching to other medications, lemborexant (7.5 ± 1.8) and suvorexant (6.9 ± 1.9) were categorized as first-line recommendations. Conclusion: Expert consensus indicates that orexin receptor antagonists and sleep hygiene education are recommended as first-line treatments in most clinical situations to treat insomnia disorder.