Association between Stimulation-Site Pain and Clinical Improvement during Repetitive Transcranial Magnetic Stimulation for Patients with Major Depressive Disorders: A Prospective Observational Study at Two Sites.

INTRODUCTION: The clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) in Japan has not been adequately investigated. Furthermore, the relationship between stimulation-site pain and the antidepressant effects of rTMS has not been thoroughly examined. Therefore, this study aimed to clarify (1) the real-world efficacy and safety of rTMS for TRD in Japan and (2) the relationship between stimulation-site pain and clinical improvement of depressive symptoms. METHODS: We conducted a retrospective observational study involving 50 right-handed patients with TRD. All patients received high-frequency rTMS for up to 6 weeks. Depressive symptoms were assessed using the Montgomery-Åsberg depression rating scale (MADRS). Pain at the stimulation site was reported by the patients using a visual analog scale (VAS) after each session. Remission and response rates at 3 and 6 weeks were calculated based on the MADRS scores. The correlation between changes in the MADRS and VAS scores was examined. RESULTS: Remission and response rates were 36% and 46%, respectively, at the end of 3 weeks, and 60% and 70%, respectively, at 6 weeks. At the end of the treatment, there was significant correlation between the reduction of MADRS and VAS scores (r = 0.42, p = 0.003). CONCLUSION: This study demonstrates the clinical efficacy of rTMS in Japan and the correlation between its antidepressant effects and stimulation-site pain.

Comparative Efficacy and Acceptability of 3 Repetitive Transcranial Magnetic Stimulation Devices for Depression: A Meta-Analysis of Randomized, Sham-Controlled Trials.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) has been employed worldwide for therapy-resistant depression. The Food and Drug Administration has approved a number of therapeutic devices for treating major depressive disorder; however, no studies have examined the differences in efficacy and acceptability among commercially available stimulation devices. The aim of our study was to compare the efficacy and acceptability of 3 stimulation devices (NeuroStar, MagPro, and Magstim) for depressive disorders. METHODS: Our study included 31 randomized sham-controlled trials of high-frequency rTMS included in the network meta-analysis by Brunoni. We calculated the risk ratio and 95% confidence intervals, comparing each device with sham for the endpoints of response rate, remission rate, and all-cause discontinuation. We then analyzed the differences among the devices in effect size for those endpoints. RESULTS: After determining the effect sizes for the endpoints, we found no statistically significant subgroup differences in the response rates, all-cause discontinuation, or remission rates among the devices (p = 0.12, p = 0.84, and p = 0.07, respectively). CONCLUSION: Our results suggest similar efficacy and acceptability for the 3 stimulation devices. Future studies need to perform head-to-head comparisons of the efficacy and acceptability of the stimulation devices for treating depression using the same stimulation protocols.

Education level is associated with neuropsychiatric symptoms in patients with amnestic-mild cognitive impairment.

BACKGROUND: We examined differences in the severity of neuropsychiatric symptom (NPS) subsyndromes according to education level among patients with amnestic-mild cognitive impairment (a-MCI) with the aim of identifying patient demographics related to NPS subsyndromes. METHODS: Overall, 140 patients with a-MCI were included. We divided the patients into three groups according to their educational level (primary education, middle education, and high education) and compared their demographics. To explore the severity of NPS subsyndromes according to educational level, we used the Neuropsychiatric Inventory (NPI) after adjustments for the Mini-Mental State Examination (MMSE) score. Finally, NPS subsyndromes that were identified as being related to educational level were further explored using a general linear model (GLM). RESULTS: Significant differences in several demographics were observed among the three groups. Among the NPS subsyndromes, the scores for aggressiveness were significantly higher in the primary and high education groups than in the middle education group, while the apathy/eating problem scores were significantly higher in the primary education group than in the other groups. The GLM analyses showed that aggressiveness was related to marital status and the Zarit Caregiver Burden Interview (ZBI-J) score, while apathy/eating problems were related to the instrumental activities of daily living (IADL) percentage, the ZBI-J score, and the education level in years. CONCLUSIONS: Among NPS subsyndromes, aggressiveness and apathy/eating problems differed according to education level in patients with a-MCI. A GLM analysis suggested that not only education level, but also various other factors should be considered when determining the need for NPS interventions.

Clinicodemographic and Psychosocial Factors Related to Presentation or Severity of Delusions of Theft among Females with Amnestic Mild Cognitive Impairment and Alzheimer's Disease.

Objectives: We examined the clinicodemographic and psychosocial factors that relate to the presentation and severity of delusions of theft among female patients with amnestic mild cognitive impairment (a-MCI) and Alzheimer's disease (AD).Methods: We enrolled a total of 177 female patients with a-MCI or AD, of whom 40 presented with delusions of theft. We compared the differences in clinicodemographic and psychosocial factors of the 40 patients (delusions of theft group) with 50 age- and Mini-Mental State Examination (MMSE)-matched controls without delusions (control group). Furthermore, we identified the factors associated with the presentation of delusions of theft using a general linear model (GLM). The severity of delusions of theft was calculated using the Neuropsychiatric Inventory Questionnaire, and correlations between the clinicodemographic and psychosocial factors were examined.Results: Between the two groups, the delusions of theft group had lower scores on the Physical Self-Maintenance Scale and instrumental activities of daily living (IADL) and higher scores on the Japanese version of the Zarit Caregiver Burden Interview (ZBI-J) than the control group. GLM analysis revealed that the IADL score was related to the presentation of delusions of theft. The severity of delusions of theft correlated with the MMSE and the ZBI-J scores in the delusions of theft group.Conclusions: The two groups had several differences regarding clinicodemographic and psychosocial factors. Furthermore, lower IADL scores were related to symptom presentation. Symptom severity correlated with cognitive functioning and caregiver burden.Clinical Implications: In the determination of treatment or care, differences in these factors should be considered.

The relationship between clients' motivation and interprofessional teamwork in forensic mental health settings.

Client motivation is regarded as a key to preventing violence behavior and positively affecting both patients and treatment staff in forensic psychiatric settings. We examined the correlation between client motivation for medical treatment and the quality of interprofessional teamwork. We surveyed 18 hospitalized forensic psychiatric patients using the IMI-J and CSQ-8J and 18 interprofessional teams from various professions using the r-CPAT, 6 and 12 months after the initial treatment. At 6 months, the correlation coefficients between the total r-CPAT scores and the total IMI-J and CSQ-8J scores were not significant. At 12 months, the correlation coefficients between the total r-CPAT scores and the total IMI-J or CSQ-8J scores were .33 and .11, respectively. The findings indicate that both clients' motivation and the quality of treatment provided by the interprofessional team improved over time. However, this study also showed that the professionals' subjective evaluation of the quality of interprofessional teamwork did not correlate with clients' subjective evaluation of satisfaction. In order to achieve client satisfaction, it is essential for professionals to address clients' needs in a timely manner and to prioritize effective communication to facilitate patient decision-making rather than merely providing advice.

Efficacy and Safety of Deep Transcranial Magnetic Stimulation in Office Workers with Treatment-Resistant Depression: A Randomized, Double-Blind, Sham-Controlled Trial.

OBJECTIVES: Major depression is a highly prevalent disorder that causes economic burden in office workers. We conducted a randomized, double-blind, sham-controlled trial to evaluate the efficacy and safety of deep transcranial magnetic stimulation (dTMS) in office workers with treatment-resistant depression. METHODS: In this study, we randomized office workers taking administrative leave for treatment-resistant major depressive disorder or bipolar disorder with current major depressive episode. dTMS treatment was applied at 120% resting motor threshold with 18 Hz over the left dorsolateral prefrontal cortex. The treatment sessions delivered a total of 1,980 pulses a day, 5 days a week, for 4-6 weeks. The primary outcome was change in the total score on the 21-item Hamilton Depression Rating Scale (HDRS-21) from baseline to the end of study in an intent-to-treat analysis. The secondary outcomes were the response and remission rates. We also assessed changes in cognitive function and adverse events. RESULTS: Forty patients were randomized to active or sham dTMS groups (1:1). The change in the total score on the HDRS-21 was more significantly improved in the active group than in the sham group at 6 weeks (p = 0.045). There were no significant differences in the response and remission rates or cognitive measures between the active and sham groups. No serious adverse events were observed in either group. CONCLUSIONS: These results suggest that dTMS might be effective and safe in office workers with treatment-resistant depression. Further well-designed studies are needed.

Sex differences in the severity of neuropsychiatric symptoms and their relationship with clinico-demographic and psychosocial factors in patients with amnestic mild cognitive impairment and mild Alzheimer's disease.

Objectives: We examined differences in the severity of neuropsychiatric symptoms (NPS) according to sex and identified NPS-related clinico-demographic and psychosocial factors among community-living patients with amnestic-mild cognitive impairment (a-MCI) or mild Alzheimer's disease (AD).Method: Overall, 111 patients (44 males, 67 females) with mild a-MCI (n = 64) or mild AD (n = 47) were included. We divided the patients according to sex and compared their clinico-demographic and psychosocial factors, explored the severity of NPS using the subscales from the Neuropsychiatric Inventory-Questionnaire (NPI-Q), and further identified variables related to NPS.Results: Significant differences in several clinico-demographic and psychosocial characteristics were observed between the sexes. The severity of delusions was higher among females (mean, 0.48; SD, 1.60) than males (mean, 0.23; SD, 1.07; p = .02), while the severity of irritability was higher among males (mean, 0.97; SD, 1.92) than females (mean, 0.49; SD, 1.40; p = .03). The severity of delusions among females was related to the duration of cognitive decline (B = 0.37, p = .03), while the severity of irritability among males was related to general cognition (B = -0.40, p = .003).Conclusion: The severity of NPS among patients with a-MCI or mild AD differed according to sex. We identified NPS-related clinico-demographic factors among these patients. Sex differences should be considered when determining the need for NPS interventions.

Anosognosia in patients with Alzheimer's disease: current perspectives.

Alzheimer's disease (AD) is a neurodegenerative disease characterised by neurocognitive impairments, especially memory impairment, as core symptoms linked to reductions in activities of daily life. As marginal symptoms, neuropsychiatric symptoms (NPSs) appear during the progressive course of the disease. A lack of self-awareness (anosognosia) of cognitive and functional impairments is often seen in patients with AD, and associations between anosognosia and other NPSs have been previously reported. To account for anosognosia pathogenesis neurocognitively, the cognitive awareness model (CAM) has been helpful for explaining the stream of events from sensory input to behavioural/affective and metacognitive outputs. According to CAM, there are three types of anosognosia: (i) primary anosognosia, (ii) executive anosognosia, and (iii) mnemonic anosognosia. These types of anosognosia are generated from different neurocognitive modulations leading to metacognitive outputs or behavioural/affective regulations. Primary anosognosia is considered to be caused by deficits in the metacognitive awareness system (MAS). While preserved MAS function is associated with milder depression and anxiety in AD, a severer depressive mood in patients with mild AD can inversely cause self-underestimation. The modulation of executive anosognosia is thought to be associated with dangerous/disinhibition behaviours and apathy among NPS sub-symptoms, via impairments of comparator mechanism (Cm) within the central executive system. Other neurobehavioral reactions linked to self-awareness include 'denying' and 'confabulation', and each of these reactions is thought to be affected by the MAS and a Cm. Denial of one's own memory impairments appears as a defensive reaction to protect against dysphoric feelings, and the confabulatory comment is instantly reaction constructed by fabrications according to misinterpretations of memory information about oneself. Similarly, the innovative development of a theoretical model (CAM) has contributed to explaining the mechanism of anosognosia and some neurobehavioral outputs from a neurocognitive perspective.

Efficacy of yokukansan compared with clonazepam for rapid eye movement sleep behaviour disorder: a preliminary retrospective study.

AIM: Rapid eye movement sleep behaviour disorder (RBD) is characterized by abnormal behaviours accordant with nightmares during rapid eye movement sleep and is considered a prodromal marker of dementia with Lewy body. Most common in the elderly population, RBD is generally treated with clonazepam (CZP), a long-term acting benzodiazepine antiepileptic. As such, alternative drugs for RBD are urgently needed to minimize the adverse effects peculiar to benzodiazepines. The efficacy of yokukansan (YKS), a traditional Japanese herbal medicine, on RBD was initially reported by Shinno et al. in 2008. However, no study has compared YKS with CZP. Therefore, this study aimed to clarify the possibility of using YKS as an alternative to CZP. METHODS: This was a retrospective cohort study conducted at Jikei University Affiliated Hospital. The subjects were selected from 36 outpatients who had been diagnosed with RBD based on the International Classification of Sleep Disorders, third edition. Of the 23 who met the inclusion criteria but not the exclusion criteria, 11 were treated with YKS monotherapy, and 12 were treated with CZP monotherapy. The primary outcome was the total score on the Japanese version of the Rapid Eye Movement Sleep Behaviour Disorder Questionnaire (RBDQ-JP), and the secondary outcomes were the scores from the eight-item Short-Form Health Survey and factors 1 and 2 of the RBDQ-JP. RESULTS: The mean total RBDQ-JP score significantly improved from 52.5 to 21.7 (P = 0.002) after treatment with YKS (mean dosage: 3.0 g/day), which was similar to the change after CZP treatment (from 43.8 to 21.3). On RBDQ-JP factor 1 (dream content), the mean score on five of six items significantly improved after treatment with YKS. There was no significant change in Short-Form Health Survey scores after treatment with either drug. Potassium concentrations were within the normal range in patients treated with YKS. CONCLUSIONS: The present results suggest that a small amount of YKS may be an alternative to CZP for RBD, without remarkable adverse events. Further study is needed to prospectively clarify the efficacy and safety of YKS in more detail.

Inter-method reliability between automatic region of interest analytic application with multi-atlas segmentation and FreeSurfer.

AIM: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the aggregation of amyloid-ß and phosphorylated tau proteins. Magnetic resonance imaging (MRI) is a useful means of detecting hippocampal atrophy. However, instead of visual inspection, objective and time-saving tools for automated region of interest (ROI) analysis are needed. Advances in MRI segmentation techniques have enabled a multi-atlas approach with fewer errors than a conventional single-atlas approach. To support the clinical application of multi-atlas segmentation, an automated ROI analytic application consisting of multi-atlas segmentation with joint label fusion and corrective learning was developed: T-Proto. In the present study, we evaluated the inter-method reliability between T-Proto and a reference ROI analytic software, FreeSurfer. METHODS: This was a database study. MRI data from 30 patients with AD were selected, and the inter-method reliability was assessed in terms of the intra-class correlation coefficient (ICC). A post-hoc comparison according to the severity of AD was also performed. RESULTS: Almost all the regional volumes estimated with T-Proto were smaller than those estimated with FreeSurfer. The regional ICC values between the two methods showed moderate to excellent reliability. A post-hoc comparison revealed a similar t-value and effect size between both methods for the hippocampus. CONCLUSION: In the present study, we showed that automated regional analysis using T-Proto was reliable in the hippocampus in terms of ICC, compared with FreeSurfer.

Framework development for the assessment of interprofessional teamwork in mental health settings.

In mental health settings, interprofessional practice is regarded as a comprehensive approach to prevent relapse and manage chronic conditions with practice of various teamwork interventions. To reinforce the potential of interprofessional teamwork, it is recommended that theories or conceptual frameworks be employed. There continues, however, to be a limited use of such approaches that assess the quality of interprofessional teamwork in mental health settings. This article aimed to present a new conceptual framework for the assessment of interprofessional teamwork based on the findings of a scoping review of the literature. This review was undertaken to identify conceptual frameworks utilised in interprofessional teamwork in mental health settings. After reviewing 952 articles, the methodological characteristics extracted from 12 articles were considered. The included studies were synthesised into the Donabedian structure-process-outcome model. The findings revealed that structural issues comprised three elements: professional characteristics, client-care characteristics, and contextual characteristics in organisations. Process issues comprised two elements: team mechanisms and community-oriented services. Finally, outcome issues comprised the following elements: clients' outcomes and professionals' outcomes. The review findings suggested possibilities for further development of how to assess the quality of interprofessional teamwork and provided information about what specific approach is required to improve interprofessional teamwork. Future research should utilise various areas and cultures to clarify the adaptation potential.

Evaluation of particles released from single-wall carbon nanotube/polymer composites with or without thermal aging by an accelerated abrasion test.

To provide data required for assessing the environmental health and safety risks of nanocomposites, abrasion-induced particle release from single-wall carbon nanotube (SWCNT)/polymer composites with or without thermal aging were evaluated by a shot blast system. First, overall composite weight loss (i.e., overall particle release) as a result of shot blasting was measured. Incorporating 5 wt% SWCNTs in polystyrene (PS) matrix was observed to reduce overall particle release by approximately 30% compared with pure PS. Heat treatment of the 5 wt% SWCNT/PS composites at 100°C for 10 days induced very slight change in overall particle release due to shot blasting. However, heat treatment at 350°C for 1 hr greatly deteriorated the abrasion resistance of the composites, enhancing overall particle release. Second, to verify the existence and form of SWCNTs released from the composites, released particles were observed by electron microscopy. Micron-sized particles with protruding SWCNTs and submicron-sized SWCNT clusters were observed in the particles released from the composites. Heat treatment of the composites at 350°C for 1 hr enhanced SWCNT release, which mainly formed clusters or rope-like bundles.

Characteristics of patients with anxiety disorder without selective serotonin reuptake inhibitor prescription over a two-year period of pharmacotherapy.

INTRODUCTION: Pharmacotherapy such as selective serotonin reuptake inhibitors (SSRIs) or serotonin-noradrenaline reuptake inhibitors is recommended for the treatment of anxiety disorders. Although there are patients with persisted symptoms of anxiety disorders who are treated with monotherapy of benzodiazepine anxiolytics without SSRIs, the characteristics of these patients are unclear. In the present study, we investigated the characteristics of patients with persisted symptoms of anxiety disorder without SSRI prescription. METHODS: From a prescription dataset covering 2018 and 2020, the prescriptions of 243 patients with anxiety disorder were analyzed. Patients were classified into two groups: SSRI non-prescription and prescription groups. RESULTS: The SSRI non-prescription group had a higher ratio of females than did the SSRI prescription group (60.1% vs. 44.6%, respectively, p = 3.12 × 10-2 ), but statistically not significant after the Bonferroni correction. No significant differences in age, body mass index, or duration of outpatient visits were found between groups. Among the independent variables, sex (female) was the only variable identified that predicted SSRI non-prescription. CONCLUSION: The present study showed that among patients with anxiety disorders, sex (female) was the only variable that predicted SSRI non-prescription.

Clinico-demographic factors associated with the treatment response to cognitive behavioral therapy for insomnia.

BACKGROUND: Cognitive behavioral therapy for insomnia (CBT-I) is among the recommended non-pharmacological treatments for patients with insomnia. While there are multiple reports on the effects of CBT-I treatment, few studies evaluating the factors associated with the treatment response to CBT-I have been reported. The present study aimed to confirm the effects of CBT-I in patients with insomnia and to examine the clinico-demographic factors that can predict the outcomes of CBT-I in these patients. METHODS: Overall, 62 patients were included in the present study. To confirm the effectiveness of CBT-I, we compared the pre- and post-CBT-I therapy values of several sleep parameters. Furthermore, to identify the clinico-demographic factors that could be predictive of the treatment response to CBT-I, we performed generalized linear model (GLM) analysis. RESULTS: The values of several sleep parameters were significantly lower after treatment than at baseline. The results of the GLM analysis revealed that sex and occupation were significantly associated with the treatment response to CBT-I. CONCLUSIONS: The present results suggest that several clinico-demographic factors should be considered in the treatment of patients with insomnia.