Publications by authors named "Yoshikazu Takaesu"

54 Publications

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.

BJPsych Open 2022 Apr 21;8(3):e83. Epub 2022 Apr 21.

Division of Neuropsychiatry, Department of Neuroscience, Yamaguchi University School of Medicine, Japan.

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.
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http://dx.doi.org/10.1192/bjo.2022.44DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9059732PMC
April 2022

Development of a 20-item questionnaire for drinking behavior pattern (DBP-20) toward personalized behavioral approaches for alcohol use disorder.

Alcohol 2022 Jun 17;101:9-16. Epub 2022 Mar 17.

Department of Neuropsychiatry, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.

Although screening tools are available for alcohol use disorders (AUD), such as the Alcohol Use Disorders Identification Test (AUDIT), these tools do not directly characterize individual drinking behavior for patients with AUD. Therefore, the aim of this study was to develop a new self-report questionnaire to identify the characteristics of drinking behavior patterns in patients with AUD.The study team developed a self-administered 20-item questionnaire for drinking behavior pattern (DBP-20) based on semi-structured interviews of patients with AUD. The DBP-20 and AUDIT were administered to 232 patients with AUD and 222 normal drinkers (1 ≤ AUDIT <20) as controls. Exploratory factor analysis of the DBP-20 was conducted for patients with AUD, followed by comparisons of its item and subscale scores between patients with AUD and controls. Correlations of AUDIT with total and subscale scores of the DBP-20 were also analyzed. Receiver operating characteristic (ROC) analyses for the DBP-20 and its subscales were performed to distinguish patients with AUD from controls.Exploratory factor analysis revealed a multidimensional 4-factor model of the DBP-20: coping with negative affect, automaticity, enhancement, and social use. Significant differences in DBP-20 total and subscale scores were observed for patients with AUD versus controls for all factors, except the social use subscale. Both the coping with negative affect and automaticity subscale scores as well as total DBP-20 scores were highly correlated with AUDIT scores. Total DBP-20 scores showed the greatest sensitivity, negative predictive value, and area under the ROC curve to distinguish patients with AUD from normal drinkers.Drinking as a means of coping with negative affect and automaticity may be specific for patients with AUD. DBP-20 may help patients with AUD to be aware of their own targeted problematic drinking behaviors and to seek their personalized behavioral approaches in a collaborative relationship with therapists.
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http://dx.doi.org/10.1016/j.alcohol.2022.03.002DOI Listing
June 2022

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

Neuropsychopharmacol Rep 2022 Mar 10. Epub 2022 Mar 10.

Department of Psychiatry, Tohoku University hospital, Miyagi, Japan.

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.
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http://dx.doi.org/10.1002/npr2.12245DOI Listing
March 2022

The characteristics of patients receiving psychotropic pro re nata medication at discharge for the treatment of schizophrenia and major depressive disorder: A nationwide survey from the EGUIDE project.

Asian J Psychiatr 2022 Mar 13;69:103007. Epub 2022 Jan 13.

Department of NeuroPsychiatry, Tokyo Metropolitan Tama Medical Center, 2-8-29 Musashidai, Fuchu, Tokyo 183-8524, Japan.

Background: Although several guidelines indicate that daily pharmacotherapy is an important part of the treatment of schizophrenia and major depressive disorder, there are few reports regarding pro re nata (PRN) prescriptions. The purpose of this study is to clarify the characteristics of patients receiving psychotropic PRN prescription for the treatment of schizophrenia and major depressive disorder.

Method: We used data from 'the effectiveness of guideline for dissemination and education in psychiatric treatment' (EGUIDE) project to evaluate the presence or absence of psychotropic PRN prescription at the time of discharge, the age and sex of patients receiving PRN prescription for each diagnosis, and the association between PRN prescription and regular daily psychotropics.

Results: The psychotropic PRN prescription ratio was 29.9% among 2617 patients with schizophrenia and 31.1% among 1248 patients with major depressive disorder at discharge. In schizophrenia, the psychotropic PRN prescription ratio was 21.6% for patients aged 65 years or older, which was lower than that of all other age groups. In major depressive disorder, the psychotropic PRN prescription ratio was 34.2% for female patients, which was significantly higher than that for male patients (25.5%). In schizophrenia, there was an association between psychotropic PRN prescription and regular use of multiple psychotropic medications.

Conclusions: Psychotropic PRN prescription was less common in elderly patients with schizophrenia and more common in female patients with major depressive disorder. In schizophrenia, psychotropic PRN prescription led to polypharmacy of psychotropics. Further studies are needed to accumulate evidence and to provide education on appropriate PRN prescriptions.
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http://dx.doi.org/10.1016/j.ajp.2022.103007DOI Listing
March 2022

Hypnotic medication use among inpatients with schizophrenia and major depressive disorder: results of a nationwide study.

Sleep Med 2022 01 22;89:23-30. Epub 2021 Nov 22.

Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Japan. Electronic address:

Study Objectives: To investigate the proportion of inpatients with schizophrenia and major depressive disorder prescribed hypnotic medication, and the association between such medication and the use of other antipsychotic agents.

Methods: This was a nationwide cross-sectional study performed as part of the 'Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment' (EGUIDE) project. Data from 2146 inpatients with schizophrenia and 1031 inpatients with major depressive disorder were analyzed. All types and dosages of psychotropic drugs were recorded and the data at the time of discharge were analyzed. Associations between the use of hypnotic medication and other antipsychotic agents were evaluated using multivariate logistic regression analyses.

Results: The proportions of schizophrenia patients who were prescribed any and two or more hypnotic agents were 55.7% and 17.6%, respectively, and the corresponding proportions for patients with major depressive disorder were 63.6% and 22.6%, respectively. In schizophrenia patients, multivariate logistic regression analyses showed that two or more antipsychotics, anticholinergic drugs, anxiolytics, and mood stabilizers/antiepileptic drugs were positively associated with the use of any hypnotic agent. In patients with major depressive disorder, multivariate logistic regression analyses revealed that two or more antidepressants, two or more antipsychotics, anxiolytics, and mood stabilizers/antiepileptic drugs were positively associated with the use of any hypnotic agent.

Conclusions: Prescription of hypnotic agents was found to be highly frequent among inpatients with psychiatric disorders. Prescription of two or more main antipsychotic agents was commonly associated with the use of hypnotic medication for both schizophrenia and major depressive disorder.
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http://dx.doi.org/10.1016/j.sleep.2021.11.005DOI Listing
January 2022

Development and field testing of a decision aid to facilitate shared decision making for adults newly diagnosed with attention-deficit hyperactivity disorder.

Health Expect 2022 02 2;25(1):366-373. Epub 2021 Dec 2.

Graduate School of Nursing, St. Luke's International University, Chuo-ku, Tokyo, Japan.

Background: The number of individuals who are diagnosed with attention-deficit hyperactivity disorder (ADHD) during adulthood has increased in recent years. However, there is still no decision aid (DA) to help adults newly diagnosed with ADHD make decisions regarding further treatments.

Objective: This study aimed to describe the development process of a DA for adults newly diagnosed with ADHD and its field testing during the shared decision-making (SDM) process in a clinical setting.

Methods: The development process involved the creation of a DA prototype using the International Patient Decision Aid Standards criteria and revision of the prototype through the stakeholders' reviews. The field testing of the DA compared scores before and after the SDM process on the service users' knowledge scale, decisional conflict scale and the Conners Adult ADHD Rating Scales.

Results: The developed DA contained options of watchful waiting with own coping skills and pharmacological treatment, which consisted of several kinds of drug options. Fifteen adults newly diagnosed with ADHD participated in the field testing. The participant decision-making quality outcomes such as their knowledge and decisional conflict improved after the SDM process. ADHD severity did not change.

Conclusion: A DA for adults with ADHD was systematically developed following the international criteria. Field testing indicated that the DA could serve as a tool to facilitate the SDM process. Further research on this DA is necessary before its routine implementation.

Patient Or Public Contribution: During the development process of the DA, the service users who had already been diagnosed with ADHD reviewed the DA prototype and provided feedback, which improved the final version of the DA.
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http://dx.doi.org/10.1111/hex.13393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8849269PMC
February 2022

Association between the examination rate of treatment-resistant schizophrenia and the clozapine prescription rate in a nationwide dissemination and implementation study.

Neuropsychopharmacol Rep 2022 03 2;42(1):3-9. Epub 2021 Dec 2.

Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.

Background: The decision to initiate clozapine treatment should be made on an individual basis and may be closely related to the early detection of treatment-resistant schizophrenia (TRS), although there is evidence that the early use of clozapine results in a better response to treatment. Therefore, we investigated the relationship between the examination rate of TRS and the prescription rate of clozapine.

Methods: After attending a 1-day educational program on schizophrenia based on the "Guidelines for the Pharmacological Treatment of Schizophrenia," we asked the participating facilities to submit records of whether or not TRS was evaluated for each patient. We calculated the clozapine prescription rate from the schizophrenic patients prescribed clozapine and all of the schizophrenic patients. Forty-nine facilities in 2017 were included in the study.

Results: There were dichotomous distributions in the examination rate of TRS and a non-normal distribution in the prescription rate of clozapine. There was a significant correlation between the prescription rate of clozapine and the examination rate of TRS (r  = 0.531, P = 1.032 × 10 ). A significant difference was found in the prescription rate of clozapine between the three groups of facilities according to the examination rate of TRS.

Conclusion: As a preliminary problem for the use of clozapine, in Japan, the examination rate of TRS varies, and there are many facilities that typically do not consider the possibility of TRS; this trend leads to a low rate of clozapine use. Clearly, further clinician training is needed for the early detection and appropriate management of TRS that includes an explanation of TRS and how to introduce clozapine therapy to patients and their families.
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http://dx.doi.org/10.1002/npr2.12218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919118PMC
March 2022

A Cross-Sectional Study of Evening Hyperphagia and Nocturnal Ingestion: Core Constituents of Night Eating Syndrome with Different Background Factors.

Nutrients 2021 Nov 22;13(11). Epub 2021 Nov 22.

Japan Somnology Center, Neuropsychiatric Research Institute, Tokyo 1510053, Japan.

This web-based cross-sectional survey aimed to elucidate the differences between the two core symptoms of night eating syndrome (NES): evening hyperphagia and nocturnal ingestion in the general Japanese population aged 16-79 years. Participants who consumed at least 25% of daily calories after dinner were defined as having evening hyperphagia. Those who consumed food after sleep initiation at least twice a week were determined to have nocturnal ingestion. Of the 8348 participants, 119 (1.5%) were categorized in the evening hyperphagia group, 208 (2.6%) in the nocturnal ingestion group, and 8024 in the non-NES group. Participants with evening hyperphagia and nocturnal ingestion had significantly higher anxiety scores ( < 0.05 and < 0.001, respectively) and depression ( < 0.001 for both) than those without NES. Multiple logistic regression analysis revealed that evening hyperphagia was significantly and independently associated with higher body mass index, shorter sleep duration, later sleep-wake schedule, and higher insomnia score, while nocturnal ingestion was significantly and independently associated with younger age, smoking habit, living alone, earlier sleep-wake schedule, and higher insomnia score. Sleep duration and sleep-wake schedule characteristics in the two groups were opposite, suggesting differences in the sleep pathophysiology mechanisms.
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http://dx.doi.org/10.3390/nu13114179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618342PMC
November 2021

Development and acceptability of a decision aid for chronic insomnia considering discontinuation of benzodiazepine hypnotics.

Neuropsychopharmacol Rep 2022 03 22;42(1):10-20. Epub 2021 Nov 22.

Department of Neuropsychiatry, Akita University Graduate School of Medicine, Akita, Japan.

Aim: To describe the development and acceptability of a decision aid (DA) for chronic insomnia considering discontinuation of benzodiazepine (BZD) and benzodiazepine receptor agonist (BZRA) hypnotics, and if discontinuing, tapering with or without cognitive behavioral therapy for insomnia (CBT-I).

Methods: We reviewed relevant literature describing chronic insomnia to identify options. We used the results of the systematic review and meta-analysis conducted previously to determine the related outcomes of two options: discontinuation of BZD/BZRA hypnotics by gradual tapering alone and discontinuation of BZD/BZRA hypnotics by gradual tapering with CBT-I. We then developed a prototype of DA following the International Patient Decision Aid Standards. A mixed methods survey was conducted to assess the acceptability among patients and healthcare providers.

Results: The prototype consisted of a description of insomnia, options of continuing or discontinuing BZD/BRZA hypnotics (if discontinuing, the options of tapering hypnotics with or without CBT-I), pros and cons of each option, and a value clarification exercise. Patients (n = 24) reported that the DA had acceptable language (79%), adequate information (71%), and well-balanced presentation (91%). Healthcare providers (n = 20) also provided favorable feedback.

Conclusion: We developed a DA for chronic insomnia considering discontinuation of BZD/BRZA hypnotics, which was acceptable for stakeholders. The developed DA was designed to support patients and healthcare providers to make a decision about whether to discontinue BZD/BRZA hypnotics.
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http://dx.doi.org/10.1002/npr2.12219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919126PMC
March 2022

Three cases of parasomnias similar to sleep terrors occurring during sleep-wake transitions from REM sleep.

J Clin Sleep Med 2022 Feb;18(2):669-675

Ureshinogaoka Samariyabito Hospital, Okinawa, Japan.

Sleep terrors are a non-rapid eye movement (NREM) sleep-related parasomnia characterized by abrupt terror with a frightening scream. However, it remains unknown whether sleep terrors occur only from NREM sleep. We evaluated 3 cases of a sleep terrors-like parasomnia that occurred exclusively during arousals from rapid eye movement (REM) sleep. These parasomnia events occurred at REM sleep-wake transitions, manifesting with screaming or crying, similar to sleep terrors, without alertness or clear orientation. The patients were all young-adult females without notable medical conditions. REM sleep behavior disorder and nocturnal frontal lobe epilepsy were not detected based on their video-polysomnographic findings. These 3 cases should be provisionally diagnosed as "Parasomnia, Unspecified" according to the third edition; however, the phenomenological diagnosis is proposed to be "Disorders of Arousal from REM Sleep." Our reported cases indicate that sleep terrors may also arise from REM sleep.

Citation: Futenma K, Inoue Y, Saso A, Takaesu Y, Yamashiro Y, Matsuura M. Three cases of parasomnias similar to sleep terrors occurring during sleep-wake transitions from REM sleep. . 2022;18(2):669-675.
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http://dx.doi.org/10.5664/jcsm.9666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804992PMC
February 2022

Characteristics of discharge prescriptions for patients with schizophrenia or major depressive disorder: Real-world evidence from the Effectiveness of Guidelines for Dissemination and Education (EGUIDE) psychiatric treatment project.

Asian J Psychiatr 2021 Sep 15;63:102744. Epub 2021 Jul 15.

Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.

Background: Monopharmacy with antipsychotics and antidepressants is the first-line treatment for schizophrenia and major depressive disorder (MDD) in most clinical guidelines, while polypharmacy with psychotropic agents in the treatment of schizophrenia is common in clinical practice. There are no detailed data on the prescription patterns for inpatients with mental illness with reliable diagnoses made by treating psychiatrists.

Methods: We gathered prescription data at discharge from 2177 patients with schizophrenia and 1238 patients with MDD from October 2016 to March 2018.

Results: The patients with schizophrenia aged between 60 and 79 were prescribed lower doses of antipsychotics and hypnotics/anxiolytics than those aged between 40 and 59. There were significant differences between the prescription rate of antipsychotics in the patients with schizophrenia and that of antidepressants in the patients with MDD. The frequency of concomitant drugs such as anti-Parkinson drugs, anxiolytics/hypnotics and mood stabilizers in the subjects with schizophrenia prescribed antipsychotic polypharmacy was significantly higher than that with monotherapy. For the patients with schizophrenia, olanzapine, risperidone, aripiprazole, quetiapine, and blonanserin were the five most prescribed antipsychotics. For the patients with MDD, mirtazapine, duloxetine, escitalopram, trazodone and sertraline were the five most prescribed antidepressants.

Conclusions: Our results showed the use of high doses of antipsychotics, high percentages of antipsychotic polypharmacy and concurrent use of hypnotics/anxiolytics in patients with schizophrenia. Notably, these data were collected before intensive instruction regarding the guidelines; therefore, we need to assess the change in the prescription pattern post guideline instruction.
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http://dx.doi.org/10.1016/j.ajp.2021.102744DOI Listing
September 2021

The relationship between insomnia symptoms and work productivity among blue-collar and white-collar Japanese workers engaged in construction/civil engineering work: a cross-sectional study.

BMC Public Health 2021 06 28;21(1):1244. Epub 2021 Jun 28.

Department of Somnology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.

Background: The situation of work productivity loss due to sleep disorders/problems among workers in industrialized societies remains unclear. The purpose of this study was to clarify the prevalence of insomnia symptoms and actual situation of work productivity by job type (white-collars/blue-collars) among construction/civil engineering workers in Japan and evaluate the association between insomnia symptoms and work productivity adjusting for sleep duration and sociodemographic, work-related, and health-related variables.

Methods: This cross-sectional study included 17,828 construction/civil engineering workers (15,837 males and 1991 females) aged 40 to 74 years in Japan. The questionnaire consisted of socio-demographic characteristics, information on work productivity (work performance and absence), respective insomnia symptoms (difficulty initiating sleep; DIS, difficulty maintaining sleep; DMS, and early morning awakening; EMA), bedtime schedule, work-related factors (job type, working hours), and perceived health condition. To identify the associated factors of work productivity, the logistic regression analyses were conducted.

Results: The percentages of workers who reported to be experiencing DIS, DMS, and EMA were 7.9, 16.3, and 13.1%, respectively. Poor work performance was associated with every insomnia symptom in both the blue-collar and white-collar workers. Meanwhile, absence was associated with DIS in blue-collar workers and both DIS and DMS in white-collar workers; however, not with EMA in both the groups. In blue-collar workers, engagement in shift work was associated with poor work performance.

Conclusions: The present study revealed the association between insomnia symptoms and work productivity, suggesting the necessity of early prevention of insomnia among both blue-collar and white-collar workers.
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http://dx.doi.org/10.1186/s12889-021-11273-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240247PMC
June 2021

Association of sleep duration on workdays or free days and social jetlag with job stress.

Psychiatry Clin Neurosci 2021 Aug 9;75(8):244-249. Epub 2021 Jun 9.

Department of Psychiatry, Tokyo Medical University, Tokyo, Japan.

Aim: The aim of this study was to investigate the impact of sleep problems on job stress in office workers.

Methods: This study included 4645 office workers from 29 companies who completed the study questionnaires between April 2017 and April 2019 in Japan. Sleep duration was assessed based on the participants' subjective sleep schedule on workdays and free days. The midpoint of sleep on free days (sleep-corrected) and social jetlag were calculated in accordance with the Munich Chronotype Questionnaire. To assess job stress, we used the 57-item Brief Job Stress Questionnaire.

Results: Multivariate logistic regression analysis revealed that the following factors were significantly associated with high job stress in office workers: a sleep duration <6 h on workdays (OR = 1.77, 95% CI = 1.46-2.15, P < 0.001), a sleep duration <6 h on free days (OR = 1.40, 95% CI = 1.05-1.87, P = 0.022), a sleep duration of at least 8 h on free days (OR = 1.31, 95% CI = 1.06-1.60, P = 0.011), and more than 2 h of social jetlag (OR = 1.33, 95% CI = 1.04-1.70, P = 0.022).

Conclusion: This study suggests that insufficient sleep, long sleep durations on free days, and social jetlag may be associated with high job stress in office workers.
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http://dx.doi.org/10.1111/pcn.13274DOI Listing
August 2021

Improving Employment Through Interpersonal Psychotherapy: A Case Series of Patients With Treatment-Refractory Depression.

Front Psychiatry 2021 23;12:617305. Epub 2021 Apr 23.

Department of Neuropsychiatry, School of Medicine, Kyorin University, Tokyo, Japan.

Patients with treatment-refractory depression (TRD) have significantly great losses in work productivity and employment. Interpersonal psychotherapy (IPT) is considered an approach for the treatment of TRD. However, the effectiveness of IPT in patients with TRD remains unclear. In this study, we report cases of TRD patients who underwent IPT after a detailed evaluation, along with their employment status. Of 112 patients who experienced 1-week examination administration for TRD at Kyorin University Hospital, which aimed to determine appropriate diagnosis and treatment approaches for each patient, four patients who met the criteria for major depressive disorder according to DSM-IV-TR and were determined suitable for IPT were included in this report. Two patients had moderate, one had mild, and one had remission levels of depressive symptoms according to the Montgomery-Asberg Depression Rating Scale at the time of admission. All four patients completed the scheduled sessions of IPT (6-16 sessions) in the outpatient clinic and achieved remission. All four patients attained full-time employment within 6 months after receiving IPT. This study suggests that the appropriate selection of IPT might be effective for TRD patients, possibly leading to positive outcomes, including work productivity and employment status.
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http://dx.doi.org/10.3389/fpsyt.2021.617305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102742PMC
April 2021

Prevalence of and factors associated with acute withdrawal symptoms after 24 weeks of eszopiclone treatment in patients with chronic insomnia: a prospective, interventional study.

BMC Psychiatry 2021 04 14;21(1):193. Epub 2021 Apr 14.

Medical Headquarters, Eisai Co., Ltd., Nishigoken-cho 13-1, Shinjuku-ku, Tokyo, 162-0812, Japan.

Background: Although long-term use of benzodiazepines and benzodiazepine receptor agonists (BZDs) has been associated with an increased risk of dependence, the incidence, details of clinical manifestations, and triggering factors of withdrawal symptoms associated with long-term BZD use at common clinical doses remain unclear.

Methods: In a multicenter, open-label study of 123 Japanese patients with insomnia, patients were given a common clinical dose of eszopiclone (2 mg) for 24 weeks, and then treatment was abruptly discontinued. Withdrawal symptoms were evaluated using the Benzodiazepine Hypnotics Withdrawal Symptom Scale (BHWSS). The Insomnia Severity Index (ISI) was used to rate insomnia severity during treatment and 2 weeks after discontinuation. Dependence and poor compliance during treatment without strict medication controls were evaluated with the Benzodiazepine Dependence Self Report Questionnaire short version (Bendep-SRQ SV) subscale sum scores for problematic use, preoccupation, and lack of compliance. Associations between the presence of clinically relevant withdrawal symptoms (BHWSS≥7) and demographic measures, ISI scores at Week 24, and Bendep-SRQ SV subscale sum scores were evaluated by multivariable stepwise logistic regression analyses.

Results: Seventy-six patients completed treatment and 2 weeks of withdrawal; eight (10.5%) had clinically relevant withdrawal symptoms. On multiple logistic regression analysis, Bendep-SRQ SV subscale sum scores were correlated with withdrawal symptoms (odds ratio, 1.650; 95% confidence interval, 1.105-2.464; p = 0.014). Exacerbation of post-discontinuation insomnia was not significantly different between patients who showed clinically relevant withdrawal symptoms and those who did not (p = 0.245).

Conclusions: Dependence and poor compliance may contribute to withdrawal symptoms with long-term BZD use. Providing guidance to ensure proper compliance is thought to be the best way to mitigate withdrawal symptoms.

Trial Registration: UMIN000024462 (18/10/2016).
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http://dx.doi.org/10.1186/s12888-021-03196-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045275PMC
April 2021

Factors Associated With Time to Achieve Employment Through Occupational Support Programs in Patients With Mood Disorders: 1 Year Naturalistic Study.

Front Psychiatry 2021 16;12:617640. Epub 2021 Mar 16.

Department of Neuropsychiatry, School of Medicine, Kyorin University, Tokyo, Japan.

Mood disorders cause significant work performance disability in sufferers and often lead to adverse employment outcomes in working individuals. The aim of this study was to explore factors associated with time to achieve employment through the occupational support program (OSP) for patients with mood disorders. The participants were patients admitted to the Kyorin university hospital from April 2016 to April 2019. Patients who met the criteria for major depressive disorder and depressive episode of bipolar I or II disorder according to DSM-5 and participated in the occupational therapy-based OSP for at least three sessions (one course) were included in this study. We collected demographic and clinical variables at the baseline of this study through medical records and OSP records; the variables included age, gender, diagnosis, scores of Quick Inventory of Depressive Symptomatology and Global Assessment of Functioning, the number of times of participation in the OSP, word count of the transcription task in the OSP, typographical deficiency, fatigue status and mood status after the OSP. The primary outcome was set as the time to achieve the employment within 1 year after the discharge. Of the 211 patients who participated in the OSP during the survey period, 49 participants met the criteria in this study. The results showed that 14 patients achieved and the other 35 patients did not achieve the employment within 1 year of discharge from the hospital. A multivariate cox regression analysis revealed that the word count of the transcription task in the OSP (HR = 1.03, 95% CI = 1.01-1.05, = 0.016) and mood status after the OSP (HR = 2.77, 95% CI = 1.18-6.51, = 0.019) were significantly associated with time to achieve the employment. In conclusion, this study suggested that work speed and mood response in the OSP could be significant predictors for achieving employment in patients with mood disorders.
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http://dx.doi.org/10.3389/fpsyt.2021.617640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007791PMC
March 2021

Reliability and validity of the Japanese version of the Biological Rhythms Interview of assessment in neuropsychiatry-self report for delayed sleep-wake phase disorder.

Sleep Med 2021 05 18;81:288-293. Epub 2021 Feb 18.

Japan Somnology Center, Institute of Neuropsychiatry, Tokyo, Japan; Department of Psychiatry Tokyo Medical University, Tokyo, Japan; Department of Somnology Tokyo Medical University, Tokyo, Japan.

Objective: The Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) might be applicable for assessing delayed sleep-wake phase disorder (DSWPD). We aimed to investigate the reliability and validity of the Japanese version of the BRIAN self-report (J-BRIAN-SR) in DSWPD patients and determine a cutoff score to identify the presence of the disorder.

Methods: We enrolled 60 newly diagnosed DSWPD outpatients and 64 age-matched healthy controls. We used Cronbach's alpha for internal reliability to evaluate J-BRIAN-SR. We confirmed the reliability of the A test and re-test using Pearson's correlation coefficient in the controls. We used confirmatory factor analysis to evaluate the factor structure of J-BRIAN-SR and referenced the Morningness-Eveningness Questionnaire (MEQ) to check concurrent validity. We analyzed the receiver operating characteristic curve (ROC) to determine the J-BRIAN-SR cutoff point for the presence of DSWPD.

Results: The 18-component scores of the J-BRIAN-SR had an overall reliability coefficient (Cronbach's alpha) of 0.82. We confirmed a high test-retest reliability using an intraclass correlation coefficient (r = 0.84). The correlation between J-BRIAN-SR and MEQ was 0.38 (p = 0.003). The J-BRIAN-SR that we extracted by exploratory factor analysis consisted of three factors. A score of 40 points provided a sensitivity of 80.0% and a specificity of 75.6% for the positivity of DSWPD.

Conclusions: The results of the present study revealed that J-BRIAN-SR is a valid and reliable instrument for screening and evaluating the severity of DSWPD. Our findings will be useful to physicians and patients in Japan and those in clinical settings.
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http://dx.doi.org/10.1016/j.sleep.2021.02.009DOI Listing
May 2021

Improvements in the degree of understanding the treatment guidelines for schizophrenia and major depressive disorder in a nationwide dissemination and implementation study.

Neuropsychopharmacol Rep 2021 06 11;41(2):199-206. Epub 2021 Mar 11.

Department of Pathology of Mental Diseases, National Center of Neurology and Psychiatry, National Institute of Mental Health, Tokyo, Japan.

Background: To implement clinical practice guidelines (CPGs), it is necessary for psychiatrists to deepen their understanding of the CPGs. The Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project is a nationwide dissemination and implementation study of two sets of CPGs for schizophrenia and major depressive disorder (MDD).

Methods: A total of 413 psychiatrists (n = 212 in 2016; n = 201 in 2017) learned the two CPGs in the education program of the EGUIDE project, and clinical knowledge of these CPGs was evaluated at baseline and after the programs. To improve the correct answer rate for clinical knowledge after the programs, we revised the lecture materials associated with items that had a low correct answer rate in 2016 and used the revised lecture materials with the CPGs in 2017. The rates of correct answers after the programs between the 2016 and 2017 groups were compared.

Results: The correct answer rate of one item on the schizophrenia CPG and one item on the MDD CPG tended to be improved (S-D5 and D-C6) and that of one on the MDD CPG was significantly improved (D-D3, P = 0.0008) in the 2017 group compared to those in the 2016 group.

Conclusions: We reported improvements in clinical knowledge of CPGs after the EGUIDE program in the 2017 group following revision of the lecture materials based on results from the 2016 group. These attempts to improve the degree of understanding of CPGs may facilitate the successful dissemination and implementation of psychiatric guidelines in everyday practice.
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http://dx.doi.org/10.1002/npr2.12173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340832PMC
June 2021

Does cognitive behavioral therapy for anxiety disorders assist the discontinuation of benzodiazepines among patients with anxiety disorders? A systematic review and meta-analysis.

Psychiatry Clin Neurosci 2021 Apr 25;75(4):119-127. Epub 2021 Feb 25.

Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan.

Long-term use of benzodiazepines (BZD) is not recommended for the treatment of anxiety disorders. Cognitive behavioral therapy (CBT) is an effective treatment option for discontinuation of BZD in patients with anxiety disorders. This systematic review and meta-analysis sought to clarify whether CBT is effective for discontinuing BZD anxiolytics in patients with anxiety disorders. This study was preregistered with PROSPERO (registration number: CRD42019125263). A literature search of major electronic databases was conducted in December 2018. Three randomized controlled trials were included in this review, and meta-analyses were performed. The proportion of discontinuing BZD anxiolytics was significantly higher in the CBT plus gradual tapering group than in the gradual tapering alone group, both in the short term (3 months after allocation; number needed to treat: 3.2, 95% confidence interval [CI]: 2.1 to 7.1; risk ratio: 1.96, 95%CI: 1.29 to 2.98, P = 0.002, three studies) and long term (6 to 12 months after allocation; number needed to treat: 2.8, 95%CI: 1.9 to 5.3; risk ratio: 2.16, 95%CI: 1.41 to 3.32, P = 0.0004, three studies). CBT may be effective for discontinuing BZD anxiolytics, both in the short term and in the long term after the allocation. Further studies with larger sample sizes are necessary to draw definitive conclusions regarding the efficacy and safety of CBT for discontinuing BZD anxiolytics in patients with anxiety disorders.
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http://dx.doi.org/10.1111/pcn.13195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048602PMC
April 2021

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.

Neuropsychopharmacol Rep 2020 09 30;40(3):281-286. Epub 2020 Jun 30.

Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

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.
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http://dx.doi.org/10.1002/npr2.12122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722678PMC
September 2020

Response to 'Efficacy and safety of bright light therapy for bipolar depression'.

Psychiatry Clin Neurosci 2020 07 9;74(7):410-411. Epub 2020 May 9.

Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan.

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http://dx.doi.org/10.1111/pcn.13010DOI Listing
July 2020

Efficacy and safety of bright light therapy for manic and depressive symptoms in patients with bipolar disorder: A systematic review and meta-analysis.

Psychiatry Clin Neurosci 2020 Apr 10;74(4):247-256. Epub 2020 Feb 10.

Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan.

Aim: This systematic review and meta-analysis evaluated whether bright light therapy (BLT) is an effective and safe treatment for manic/depressive symptoms and a preventive measure for recurrent mood episodes in patients with bipolar disorder.

Methods: A literature search of major electronic databases was conducted in June 2019, including all published articles up to that date. Two researchers independently selected relevant publications, extracted data, and evaluated methodological quality according to the Cochrane criteria.

Results: Six randomized controlled trials (RCT) evaluated the efficacy of BLT for bipolar depression. A meta-analysis found no significant differences between BLT and placebo for the following outcomes: (i) rates of remission from depressive episodes (risk ratio [RR]: 1.81, 95% confidence interval [CI]: 0.43 to 7.64, P = 0.42); (ii) depressive symptom scores (standardized mean difference: -0.25, 95%CI: -0.74 to 0.23, P = 0.30); and (iii) rates of manic switching (RR: 1.00, 95%CI: 0.28 to 3.59, P = 0.26). The sensitivity analysis for studies with low overall indirectness did show a significant antidepressant effect for BLT (RR: 3.09, 95%CI: 1.62 to 5.90, P = 0.006). No RCT investigated the effect of BLT in preventing the recurrence of mood episodes in the euthymic state or in improving manic symptoms in the manic state. No severe adverse events were reported.

Conclusion: While a meta-analysis was unable to demonstrate the efficacy of BLT for bipolar depression, a sensitivity analysis did show a significant effect. Further well-designed studies are needed to clarify the effectiveness of BLT, not only for the depressive state but also for other states, in the treatment of bipolar disorder.
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http://dx.doi.org/10.1111/pcn.12976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187384PMC
April 2020

Psychosocial intervention for discontinuing benzodiazepine hypnotics in patients with chronic insomnia: A systematic review and meta-analysis.

Sleep Med Rev 2019 12 1;48:101214. Epub 2019 Oct 1.

Department of Neuropsychiatry, Akita University Graduate School of Medicine, Japan; Department of Psychophysiology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Japan; International Institute for Integrative Sleep Medicine, University of Tsukuba, Japan.

Long-term benzodiazepine (BZD) use is not recommended in the treatment of chronic insomnia, and psychosocial interventions, particularly cognitive behavioral therapy for insomnia (CBT-I), are a potential treatment option for discontinuing BZDs. This systematic review and meta-analysis aimed to clarify whether psychosocial interventions are effective for discontinuing BZD hypnotics in patients with chronic insomnia. A literature search of major electronic databases was conducted up to July 2018. Two researchers independently selected relevant publications, extracted data, and evaluated methodological quality according to the Cochrane criteria. Eight randomized-controlled trials, all of which evaluated CBT-I, were included in this review, and meta-analyses were performed. The results indicated that short-term (≤3 mo) CBT-I plus gradual tapering was more effective than gradual tapering alone for discontinuing BZDs hypnotics (risk ratio: 1.68, 95% confidence interval [CI]: 1.19-2.39, p = 0.003) and for improving insomnia symptoms (g: -0.69, 95% CI: -1.09 - -0.28, p = 0.0009). However, the long-term (12 mo) efficacy of CBT-I for discontinuing BZDs was not significant (risk ratio: 1.67, 95% CI: 0.91-3.07, p = 0.10). Thus, CBT-I is effective for discontinuing BZD hypnotics for ≤3 mo. Further studies are needed to clarify the long-term efficacy of psychosocial interventions for discontinuing BZD hypnotics.
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http://dx.doi.org/10.1016/j.smrv.2019.101214DOI Listing
December 2019

Seven-day shared decision making for outpatients with first episode of mood disorders among university students: A randomized controlled trial.

Psychiatry Res 2019 11 30;281:112531. Epub 2019 Aug 30.

Department of Neuropsychiatry, School of Medicine, Kyorin University, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan. Electronic address:

Providing appropriate treatment to patients with a first episode of mood disorders is crucial for recovery from the disorders. Although shared decision making (SDM) has been proposed as a promising model in psychiatric practice, an appropriate SDM approach has not yet been established. The aim of the current study was to evaluate the effects of an originally developed seven-day SDM program for outpatients with a first episode of mood disorders among university students. University students with a first episode of mood disorders were randomly allocated into two arms: SDM and control. The participants in the SDM arm received the seven-day SDM program, which included option presentation consultation, external deliberation with a decision aid booklet, decision coaching by a nurse, and decision-making consultation. The control arm received usual care. The primary outcome was patient-perceived involvement. We enrolled 88 participants. Compared with usual care, the SDM program significantly improved patient-perceived involvement in treatment decision making without taking up clinicians' time. The program did not lead to worse symptoms of mood disorders. In conclusion, sharing treatment decision making with university students with a first episode of mood disorders is feasible.
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http://dx.doi.org/10.1016/j.psychres.2019.112531DOI Listing
November 2019

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.

Psychiatry Clin Neurosci 2019 Oct 22;73(10):642-648. Epub 2019 Aug 22.

Department of Neuropsychiatry, Kanazawa Medical University, Ishikawa, Japan.

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.
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http://dx.doi.org/10.1111/pcn.12911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852015PMC
October 2019

Ability of suvorexant to prevent delirium in patients in the intensive care unit: a randomized controlled trial.

Acute Med Surg 2018 Oct 19;5(4):362-368. Epub 2018 Aug 19.

Department of Emergency and Critical Care Medicine Tokyo Medical University Tokyo Japan.

Aim: There are no effective, tolerable, and established medications for preventing delirium in critically ill patients admitted to the intensive care unit (ICU). We investigated whether suvorexant was effective in preventing ICU delirium.

Methods: This randomized controlled study evaluated 70 adult patients (age ≥20 years) admitted to the mixed medical ICU of the Tokyo Medical University Hospital (Tokyo, Japan) between May 2015 and February 2017. Patients were randomized using a sealed envelope method to receive either suvorexant ( = 34; 15 mg for elderly patients and 20 mg for younger adults) or conventional treatment ( = 36) for a 7-day period. The primary outcome was delirium incidence based on the definition in the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders.

Results: No significant between-group differences were observed in the demographic or clinical characteristics. Kaplan-Meier estimates revealed that time to delirium onset was significantly longer in the suvorexant group than in the conventional group ( < 0.05).

Conclusion: Suvorexant might be effective in preventing delirium in ICU patients.
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http://dx.doi.org/10.1002/ams2.368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167389PMC
October 2018

Circadian rhythm in bipolar disorder: A review of the literature.

Psychiatry Clin Neurosci 2018 Sep 4;72(9):673-682. Epub 2018 Jul 4.

Department of Neuropsychiatry, Kyorin University, School of Medicine, Tokyo, Japan.

Sleep disturbances and circadian rhythm dysfunction have been widely demonstrated in patients with bipolar disorder (BD). Irregularity of the sleep-wake rhythm, eveningness chronotype, abnormality of melatonin secretion, vulnerability of clock genes, and the irregularity of social time cues have also been well-documented in BD. Circadian rhythm dysfunction is prominent in BD compared with that in major depressive disorders, implying that circadian rhythm dysfunction is a trait marker of BD. In the clinical course of BD, the circadian rhythm dysfunctions may act as predictors for the first onset of BD and the relapse of mood episodes. Treatments focusing on sleep disturbances and circadian rhythm dysfunction in combination with pharmacological, psychosocial, and chronobiological treatments are believed to be useful for relapse prevention. Further studies are therefore warranted to clarify the relation between circadian rhythm dysfunction and the pathophysiology of BD to develop treatment strategies for achieving recovery in BD patients.
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http://dx.doi.org/10.1111/pcn.12688DOI Listing
September 2018

Comprehensive assessment of the impact of life habits on sleep disturbance, chronotype, and daytime sleepiness among high-school students.

Sleep Med 2018 04 26;44:12-18. Epub 2017 Nov 26.

Department of Psychiatry, Tokyo Medical University, Tokyo, Japan.

Objective: Sleep affects adolescents in various ways. However, the effects of multiple factors on sleep hygiene remain unclear. A comprehensive assessment of the effects of life habits on sleep in high-school students was conducted.

Methods: A cross-sectional survey of 344 high school students (age range 15-17; 171 boys, 173 girls) in Tokyo, Japan was conducted in 2015. Complete responses were provided by 294 students. Demographic variables, Pittsburgh Sleep Quality Index (PSQI), diurnal type scale, Pediatric Daytime Sleepiness Scale (PDSS), and life habits such as dinnertime, viewing electronic displays, caffeine intake, sunlight in the morning, and the brightness of the room in the night were asked.

Results: The mean scores were PSQI: 5.9 (±2.3), PDSS: 19.0 (±5.8), and the diurnal type scale: 16.7 (±3.4). Using an electronic display in bed (OR = 3.01; (95%CI) 1.24-7.30), caffeine intake at night always (OR = 2.22; 1.01-4.90), and waking up before dawn (OR = 3.25; 1.34-7.88) were significantly associated with sleep disturbance. Irregular timing of the evening meal (OR = 2.06; 1.10-3.84) and display viewing within 2 h before bedtime (OR = 2.50; 1.01-6.18) or in bed (OR = 3.60; 1.41-9.21) were significantly associated with excessive daytime sleepiness. Using an electronic display within 2 h before bedtime (OR = 2.64; 1.10-6.38) or in bed (OR = 3.50; 1.40-8.76) and a living room which is bright at night (OR = 1.89; 1.06-3.36) were significantly associated with eveningness.

Conclusion: Each type of sleep-related problem had its own associated life habit factors.
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http://dx.doi.org/10.1016/j.sleep.2017.10.011DOI Listing
April 2018

Circadian Rhythm Sleep-Wake Disorders Predict Shorter Time to Relapse of Mood Episodes in Euthymic Patients With Bipolar Disorder: A Prospective 48-Week Study.

J Clin Psychiatry 2018 Jan/Feb;79(1)

Department of Psychiatry, Tokyo Medical University, Tokyo, Japan.

Objective: Circadian rhythm dysfunction has been considered to be common in bipolar disorder (BD) and plays an important role in mood dysregulation in this disorder. However, no study has investigated whether circadian rhythm dysfunction would affect the clinical course of BD. The aim of this study was to test the hypothesis that circadian rhythm dysfunction could be a predictor of relapse in euthymic BD patients.

Methods: One hundred four euthymic outpatients with BD diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), participated in this prospective follow-up study from August 2014 to April 2015. At baseline, data on demographic variables and clinical descriptive variables of bipolar disorder were ascertained via clinical interviews. The diagnoses of circadian rhythm sleep-wake disorders (CRSWDs) were made based on participants' sleep logs for 4 weeks and according to the International Classification of Sleep Disorders, Third Edition (ICSD-3). The BD symptoms of the subjects were evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) scores every 4 weeks throughout the 48-week study period. Relapse of BD was defined as scores higher than the cutoff points (MADRS score ≥ 13 and YMRS score ≥ 7). The primary outcome was time to relapse of mood episodes.

Results: Thirty-four subjects met criteria for CRSWD at baseline, most frequently delayed sleep-wake phase disorder (n = 27). Of the total 104 subjects, 51 (49.0%) experienced relapse during the 48-week follow-up period. Multivariate Cox hazard regression analyses revealed that 2 or more previous mood episodes within the past year and comorbidity of CRSWD were significantly associated with the time to relapse of mood episodes (P < .001).

Conclusions: Comorbid CRSWD, mainly delayed sleep-wake phase disorder, could be a significant predictor of relapse in BD patients.
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http://dx.doi.org/10.4088/JCP.17m11565DOI Listing
July 2019
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