A knowledge-based simple education program for patients with epilepsy in Japan: Effects sustained after the program implementation.

PURPOSE: To investigate the effects of an original education program on patients with epilepsy (PWE). The effects on knowledge about epilepsy, attitude to epilepsy, depression scales, and quality of life were investigated. METHOD: Thirty-five PWE participated in a lecture-style educational program using an original knowledge-oriented textbook. All patients were administered a total of four rating scales: the Knowledge about Epilepsy Scale (KES), the Attitude toward Epilepsy Scale (AES), and the Japanese version of the Quality of Life in Epilepsy Inventory (QOLIE-31-P), the Beck Depression Inventory (BDI). The KES and AES of patients (pKES and pAES) were compared to those of medical students (St) and residents (Rd). RESULTS: After education, pKES improved and showed significant differences among pre-and post-education and six months later. Before education, pKES was inferior to St and Rd. However, after education, pKES changed and became superior to St and Rd. Six months later, the advantage was lost, but not significantly. PAES also improved after education, with significant differences before, after, and six months later after education. PAES was statistically inferior to St and Rd before education, but the difference disappeared after education, and the effect persisted after six months. The non-depressed (BDI < 20) and depressed groups (BDI â‰§ 20) improved in the KES after education. About the AES, the non-depressive group has a statistical tendency, but not the depressive group. At six months, the depressed group's AES is significantly lower than the non-depressed group. CONCLUSION: While correct knowledge about epilepsy can improve attitudes and perceptions of epilepsy in PWE, special measures are needed for PWE with depression.

Impact of Selected Initial Titration Schedules on Safety and Long-Term Effectiveness of Lamotrigine for the Treatment of Mood Disorders.

PURPOSE: Lamotrigine (LTG) is used for treatment of mood disorders, but it is associated with the risk of rash occurrence in the initial administration phase. Although slow titration reduces this risk, its effectiveness in the treatment of mood disorders has not been verified. The effects of titration method on the safety and effectiveness of LTG for the treatment of mood disorders were examined in this study. METHODS: This retrospective cohort study included 312 patients with mood disorders who underwent initiation of LTG therapy. Data regarding baseline demographics, titration schedules, concomitant medications, and time to and cause of discontinuation of LTG were collected. A multivariate analysis was used to evaluate the effects of the titration schedules. The 12-month effectiveness was also evaluated. RESULTS: The 12-month discontinuation rate of LTG was 16.7%. The most frequent cause of discontinuation was development of a rash (47.7%, n = 312). Fast titration (adjusted odds ratio, 8.15) significantly increased the risk of rash development, and slow titration (adjusted odds ratio, 0.29) significantly decreased this risk. The time to all-cause discontinuation was not significantly different between the slow and standard titration groups (n = 303). After 12 months of treatment, the condition of 46.7% patients were rated much or very much improved using CGI-C. CONCLUSIONS: Although slow titration of LTG reduces the occurrence of a rash, it is not more effective than standard titration in the long term. Optimizing the initial LTG titration schedule for patients with mood disorders is challenging.

Optimal dose determination of enerisant (TS-091) for patients with narcolepsy: two randomized, double-blind, placebo-controlled trials.

BACKGROUND: The histamine H3 receptor has emerged as one of the most promising targets of novel pharmacotherapy for narcolepsy. Studies now aim to investigate the optimal dose of enerisant, a novel H3 antagonist/inverse agonist, for the treatment of excessive daytime sleepiness in patients with narcolepsy. METHODS: We conducted two phase 2, fixed-dose, double-blind, randomized, placebo-controlled trials in patients with narcolepsy. The first phase 2 study (Study 1) was conducted to investigate the efficacy and safety of enerisant at dosages of 25, 50, and 100 mg/day administered for 3 weeks based on the results of a phase 1 study conducted on healthy volunteers. The primary endpoint was mean sleep latency in maintenance of wakefulness test (MWT), and the secondary endpoint was the total score on the Epworth Sleepiness Scale (ESS). The dosages of enerisant in the second phase 2 study (Study 2) were set at 5 and 10 mg/day based on the simulation of receptor occupancy results from positron emission tomography study. RESULTS: Forty-six and fifty-three patients were randomized in Study 1 and Study 2, respectively. The efficacy of enerisant was partially confirmed in Study 1 with ESS; however, the doses were not tolerated, and there were many withdrawals due to adverse events (mainly insomnia, headache, and nausea). The doses in Study 2 were well tolerated, with a lower incidence of adverse events in Study 2 than in Study 1, although the efficacy could not be confirmed with MWT and ESS in Study 2. CONCLUSIONS: The optimal dose of enerisant could not be determined in these two studies. Although enerisant has a favorable pharmacokinetic profile, it is thought to have large interindividual variabilities in terms of efficacy and safety, suggesting the necessity of tailored dosage adjustments. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03267303 ; Registered 30 August 2017 (Study 2). Japic identifier: JapicCTI-142529 ; Registered 7 May 2014 (Study 1) and JapicCTI-173689 ; Registered 30 August 2017, https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?clinicalTrialId=29277 (Study 2).

A large survey of nocturia related to sleep quality and daytime quality of life in a young Japanese population: NOCTURNE study.

AIMS: Nocturia, due to nocturnal polyuria and other conditions associated with nocturnal voiding, affects sleep quality and daytime quality of life (QOL). We aimed to investigate the relationship among nocturia, sleep quality, and daytime QOL in a young Japanese population. METHODS: This epidemiological study analyzed data from a retrospective data set containing sleep data from wearable devices worn by 9446 Japanese users and a prospective data set containing answers to a 10-item questionnaire completed by a subset of 605 users in the retrospective dataset. We recorded the first uninterrupted sleep period (FUSP), total sleep time (TST), number of nocturnal voids, sleep quality, daytime QOL, bothering nocturnal voids, and early wake-ups in the morning. RESULTS: The subjects were 18-65 years old. The mean TST was 6.7 ± 0.9 h, and the mean number of wake-ups was 2.11 ± 1.1. FUSP and TST decreased (from 334 ± 114 to 173 ± 74 min and 5.9 ± 1.0 to 5.5 ± 1.0 h, respectively) with an increasing number of nocturnal voids, and the change was statistically significant. Logistic regression analysis showed a statistically significant relationship between nocturia and FUSP and the number of wake-ups. CONCLUSION: Nocturia has close relationships with FUSP and the number of wake-ups and can result in decreased daytime QOL in young Japanese people.

Comparison of changes in the oxygenated hemoglobin level during a 'modified rock-paper-scissors task' between healthy subjects and patients with schizophrenia.

AIM: The purpose of this study, using single-event-related near-infrared spectroscopy (NIRS), was to examine the psychophysiological and social function assessment of 30 schizophrenic patients during a modified rock-paper-scissors task. METHODS: We set up a screen in front of the subjects, on which pictures of hand-gestures for rock, paper, and scissors were randomly presented. Subjects were asked to give verbal answers under the conditions of win, lose, and draw, respectively. Using the 44-channel NIRS system, we evaluated the maximum amplitude of oxygenated hemoglobin, latency, and the area based on the arithmetic mean of resulting values after the task between 30 outpatients with schizophrenia and 30 healthy subjects, and analyzed the frontal pole area, dorsolateral prefrontal region, and parietal association area as regions of interest (ROI). RESULTS: In schizophrenic patients, oxygenated hemoglobin changes (Δoxy-Hb) when losing the task showed a significantly lower level of Δoxy-Hb in ROI than controls. In addition, a significant positive correlation was observed between the Global Assessment of Functioning Scale and Δoxy-Hb in ROI, and a significant negative correlation was observed between the Negative Syndrome scale of the Positive and Negative Syndrome Scale and Δoxy-Hb in ROI. CONCLUSION: From these results, we conclude that Δoxy-Hb levels when performing the modified rock-paper-scissors task assessed using NIRS may be a useful psychophysiological marker to evaluate the cognitive and social functions of schizophrenic patients.

Characteristics of oxygenated hemoglobin concentration change during pleasant and unpleasant image-recall tasks in patients with depression: Comparison with healthy subjects.

AIM: Patients with major depressive disorder (MDD) have been reported to show cognitive impairment in attention, cognition control, and motivation. The prefrontal cortex plays an important role in the pathophysiology of depression. Neurophysiological abnormalities have been examined in MDD patients by several neuroimaging studies. However, the underlying neural mechanism is still unclear. We evaluated brain function during pleasant and unpleasant image-recall tasks using multichannel near-infrared spectroscopy (NIRS) in MDD patients. METHODS: The subjects were 25 MDD patients and 25 age- and sex-matched healthy controls. Patients were classified according to DSM-IV-TR criteria. We measured the oxygenated hemoglobin concentration change (δoxyHb) in the forehead and temporal lobe during image-recall task with pleasant (e.g., puppy) and unpleasant (e.g., snake) images using NIRS. To check whether all subjects understood the task, they were asked to draw pictures of both image tasks after NIRS measurement. RESULTS: The δoxyHb in the healthy group was significantly higher than that in the MDD group in the bilateral frontal region during the unpleasant condition. A significant negative correlation between the Hamilton Rating Scale for Depression score and δoxyHb was observed in the left frontal region during the unpleasant condition. CONCLUSION: We suggest that image-recall tasks related to emotion measured by NIRS might be a visually useful psychophysiological marker to understand the decrease in the frontal lobe function in MDD patients. In particular, we suggest that the decrease in δoxyHb in the left frontal lobe is related to the severity of depression.

New susceptibility variants to narcolepsy identified in HLA class II region.

Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness, cataplexy and rapid eye movement sleep abnormalities, is tightly associated with human leukocyte antigen HLA-DQB1*06:02. DQB1*06:02 is common in the general population (10-30%); therefore, additional genetic factors are needed for the development of narcolepsy. In the present study, HLA-DQB1 in 664 Japanese narcoleptic subjects and 3131 Japanese control subjects was examined to determine whether HLA-DQB1 alleles located in trans of DQB1*06:02 are associated with narcolepsy. The strongest association was with DQB1*06:01 (P = 1.4 × 10(-10), odds ratio, OR = 0.39), as reported in previous studies. Additional predisposing effects of DQB1*03:02 were also found (P = 2.5 × 10(-9), OR = 1.97). A comparison between DQB1*06:02 heterozygous cases and controls revealed dominant protective effects of DQB1*06:01 and DQB1*05:01. In addition, a single-nucleotide polymorphism-based conditional analysis controlling for the effect of HLA-DQB1 was performed to determine whether there were other independent HLA associations outside of HLA-DQB1. This analysis revealed associations at HLA-DPB1 in the HLA class II region (rs3117242, P = 4.1 × 10(-5), OR = 2.45; DPB1*05:01, P = 8.1 × 10(-3), OR = 1.39). These results indicate that complex HLA class II associations contribute to the genetic predisposition to narcolepsy.

Inquiring about insomnia may facilitate diagnosis of depression in the primary care setting.

AIM: Depression is often undiagnosed in primary care. Asking about sleep status is much easier than asking about mood. This study was conducted to examine the relation between insomnia and depression. METHODS: New patients aged 35-64 years were recruited from internal medicine clinics in Japan. Self-administered questionnaires were employed. Depression was evaluated by the Zung Self-Rating Depression Scale and the Profile of Mood States. Sleep status was investigated using the Pittsburgh Sleep Quality Index. Likelihood ratios of insomnia for depression were calculated. To assess the relation between insomnia and depression independent of confounding factors, adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using multiple logistic regression analyses. RESULTS: Among 598 subjects, 153 (25.6%) were assessed as having depression. 'Very bad sleep quality, with difficulty falling asleep within 30 min ≥3 times/week' showed a positive likelihood ratio of 20.36 (95%CI, 2.53-164) while 'not very good sleep quality' had a negative likelihood ratio of 0.32 (95%CI, 0.14-0.72). Adjusted for sex, age, underlying diseases, major life events, lifestyle habits, and relationship problems, significant OR for depression were observed for 'difficulty falling asleep within 30 min ≥3 times/week' (OR, 2.53; 95%CI, 1.07-5.98), 'waking up in the middle of the night or early morning ≥3 times/week' (OR, 3.09; 95%CI, 1.58-6.05), and 'fairly bad sleep quality' (OR, 3.65; 95%CI, 1.34-9.96). CONCLUSION: Inquiring about the weekly frequency of difficulty 'falling asleep within 30 min,' 'waking up in the middle of the night or early morning,' and 'sleep quality' may help to diagnose depression.

Evaluation of changes in oxyhemoglobin during Shiritori task in elderly subjects including those with Alzheimer‧s disease.

BACKGROUND: In recent years, as the prevalence of Alzheimer‧s disease (AD) has increased rapidly, demand has increased for early detection and treatment. Therefore, discovery and treatment intervention at the mild cognitive impairment stage are important. Dysfunction of the working memory is known to be conspicuously present in AD patients or mild cognitive impairment subjects from an early stage. Near-infrared spectroscopy (NIRS) is a method to measure hemoglobin concentration changes during an activation task. In the present study, we evaluated the cognitive function of elderly subjects, including those with AD, by means of NIRS. METHODS: The subjects were divided into three groups-the AD group, the intermediate group, and the healthy group (HG)-based on assement of dementia using the Hasegawa‧s Dementia Scale-Revised, Mini-Mental State Examination, and Clinical Dementia Rating. The intermediate group was divided into two groups-the high score group (HSMG) and the low score group (LSMG)-based on Hasegawa‧s Dementia Scale-Revised and Mini-Mental State Examination scores. In this study, during Shiritori tasks using single-event-related NIRS, we analyzed oxyhemoglobin changes in an area, the peak amplitude, and latency, and compared them among four groups: AD group, HSMG, LSMG, and HG. RESULT: In the AD group, the area at left channel (Ch)9, 11, and 19, the area at right Ch22, and the peak ampulitude at left Ch11 and 19 and right Ch5,12, and 22 were significantly smaller than those in HSMG and HG. Furthermore, the latency of the AD group was significantly longer than that of HSMG and HG at all region of interests. However, no significant difference was observed between the AD group and LSMG. CONCLUSION: These findings suggest that analysis of changes in oxyhemoglobin during Shiritori tasks may be a useful neuropsychological index for the early diagnosis of AD. Detailed studies will be conducted in LSMG to facilitate the early introduction of NIRS as a screening tool for cognitive impairment.

A polymorphism in CCR1/CCR3 is associated with narcolepsy.

Etiology of narcolepsy-cataplexy involves multiple genetic and environmental factors. While the human leukocyte antigen (HLA)-DRB1*15:01-DQB1*06:02 haplotype is strongly associated with narcolepsy, it is not sufficient for disease development. To identify additional, non-HLA susceptibility genes, we conducted a genome-wide association study (GWAS) using Japanese samples. An initial sample set comprising 409 cases and 1562 controls was used for the GWAS of 525,196 single nucleotide polymorphisms (SNPs) located outside the HLA region. An independent sample set comprising 240 cases and 869 controls was then genotyped at 37 SNPs identified in the GWAS. We found that narcolepsy was associated with a SNP in the promoter region of chemokine (C-C motif) receptor 1 (CCR1) (rs3181077, P=1.6×10(-5), odds ratio [OR]=1.86). This rs3181077 association was replicated with the independent sample set (P=0.032, OR=1.36). We measured mRNA levels of candidate genes in peripheral blood samples of 38 cases and 37 controls. CCR1 and CCR3 mRNA levels were significantly lower in patients than in healthy controls, and CCR1 mRNA levels were associated with rs3181077 genotypes. In vitro chemotaxis assays were also performed to measure monocyte migration. We observed that monocytes from carriers of the rs3181077 risk allele had lower migration indices with a CCR1 ligand. CCR1 and CCR3 are newly discovered susceptibility genes for narcolepsy. These results highlight the potential role of CCR genes in narcolepsy and support the hypothesis that patients with narcolepsy have impaired immune function.

Antipsychotics for delirium in the general hospital setting in consecutive 2453 inpatients: a prospective observational study.

OBJECTIVE: Attention to risk of antipsychotics for older patients with delirium has been paid. A clinical question was whether risk of antipsychotics for older patients with delirium would exceed efficacy of those even in the general hospital setting. METHODS: A prospective observational study proceeded over a 1-year period at 33 general hospitals, where at least one psychiatrist worked full time. Subjects were patients who developed delirium during their admission due to acute somatic diseases or surgery, and who received antipsychotics for delirium. The primary outcome was rates and kinds of serious adverse events. RESULTS: Among 2834 patients who developed delirium, 2453 patients received antipsychotics, such as risperidone (34%), quetiapine (32%), and parenteral haloperidol (20%), for delirium. Out of 2453 patients, 22 serious adverse events (0.9%) were reported. Aspiration pneumonia was the most frequent (17 patients, 0.7%), followed by cardiovascular events (4 patients, 0.2%) and venous thromboembolism (1 patient, 0.0%). There was no patient with a fracture or intracranial injury due to a fall. No one died because of antipsychotic side effects. The mean Clinical Global Impressions-Improvement Scale score was 2.02 (SD 1.09). Delirium was resolved within 1 week in more than half of the patients (54%). CONCLUSIONS: In the general hospital setting under management including fine dosage adjustment and early detection of side effects, risk of antipsychotics for older patients with delirium might be low, in contrast to antipsychotics for dementia in the nursing home or outpatient settings. A point may be not how to avoid using antipsychotics but how to monitor their risk.

Evaluation of P300 components for emotion-loaded visual event-related potential in elderly subjects, including those with dementia.

AIM: In the present study, the P300 component of the emotion-loaded visual event-related potential in response to photographs of babies crying or smiling was measured to evaluate cognitive function in elderly subjects, including those with dementia. METHODS: The subjects were 48 elderly people who consulted a memory disorder clinic. The visual event-related potential was measured using oddball tasks. Brain waves were recorded from four sites. We analyzed the P300 amplitude and latency. Subjects were divided into three groups (the dementia with Alzheimer's disease group [ADG]; the intermediate group [MG], and the healthy group [HG]) based on the Revised Hasegawa Dementia Scale, Mini-mental State Examination scores and the Clinical Dementia Rating. RESULTS: For all subjects, there was a significant positive correlation between P300 latency and Z-score of voxel-based specific regional analysis for Alzheimer's disease for crying or smiling faces. There was a negative correlation between P300 amplitude and Z-score for the crying face. MG subjects were divided into two groups (high risk: HRMG, low risk: LRMG) based on Z-scores (HRMG ≥ 2.0). The P300 amplitude of ADG was significantly smaller than that of HG, and the P300 latency of ADG was significantly longer than those of other groups for crying or smiling faces. The P300 latency of HRMG was significantly longer than that of LRMG for the smiling face. Furthermore, the P300 latency for the crying face was significantly shorter than that for the smiling face in HG and ADG. CONCLUSION: These findings suggest that analysis of P300 components of the emotion-loaded visual event-related potential may be a useful neuropsychological index for the diagnosis of Alzheimer's disease and high-risk subjects.

A randomized, double-blind, placebo-controlled, crossover study of respiratory safety of lemborexant in moderate to severe obstructive sleep apnea.

STUDY OBJECTIVES: To evaluate the respiratory safety of lemborexant among adults and older adults with moderate to severe obstructive sleep apnea (OSA). METHODS: E2006-A001-113 (Study 113; NCT04647383) was a double-blind, two-period crossover, placebo-controlled study in adults (ages ≥ 45 to ≤ 90 years, n = 33) with moderate (apnea-hypopnea index [AHI] score ≥ 15 to < 30 events/h, n = 13) or severe (AHI ≥ 30 events/h, n = 20) OSA. Participants were randomized to lemborexant 10 mg (LEM10) or placebo (PBO) for two treatment periods of 8 nights with a ≥ 14-day washout period. AHI and peripheral oxygen saturation were evaluated after treatment on Day 1 (after a single dose) and Day 8 (after multiple doses). RESULTS: No significant differences in AHI were observed after single and multiple doses of LEM10 compared with PBO in participants with moderate to severe OSA (least-squares mean: single-dose LEM10, 41.7; PBO, 44.8; multiple-dose LEM10, 44.9; PBO, 45.7). In addition, there were no significant differences between treatments in peripheral oxygen saturation (least-squares mean: single-dose LEM10, 93.0; PBO, 93.1; multiple-dose LEM10, 93.1; PBO, 93.4). Further, there were no significant differences between treatments in percentage of total sleep time with peripheral oxygen saturation < 90%, < 85%, or < 80%. No significant differences were observed between treatments when AHI and peripheral oxygen saturation outcomes were analyzed by OSA severity. Altogether, 6/33 (18.2%) participants receiving LEM10, vs 3/33 (9.1%) PBO, reported treatment-emergent adverse events, mostly mild in severity. CONCLUSIONS: LEM10 demonstrated respiratory safety and was well tolerated with single-dose and multiple-dose administration in participants with moderate to severe OSA. This suggests that LEM may be a treatment option for patients with OSA and comorbid insomnia. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: A Study to Evaluate the Respiratory Safety of Lemborexant in Adult and Elderly Participants With Moderate to Severe Obstructive Sleep Apnea and in Adult and Elderly Participants With Moderate to Severe Chronic Obstructive Pulmonary Disease; URL: https://clinicaltrials.gov/ct2/show/NCT04647383; Identifier: NCT04647383. CITATION: Cheng JY, Lorch D, Lowe AD, et al. A randomized, double-blind, placebo-controlled, crossover study of respiratory safety of lemborexant in moderate to severe obstructive sleep apnea. J Clin Sleep Med. 2024;20(1):57-65.

Trends in the multiple prescriptions of hypnotic drugs in a university outpatient in Japan.

AIMS: In Japan, the daily dosage of hypnotic drugs for insomnia treatment is increasing year by year, and over-dependence on treatment with hypnotic drugs is a major problem. This study aimed to examine the factors related to the elimination of prescriptions of three or more hypnotic drugs within 1 year in our clinic. METHODS: We conducted two surveys. Survey ① assessed the frequency of prescriptions of three or more hypnotic drugs by retrospectively reviewing the medical records of all patients who visited general and psychiatric outpatient clinics from January 2013 to March 2019. Survey ② assessed changes in prescriptions of hypnotic and psychotropic drugs within the subsequent year by retrospectively reviewing the medical records of all patients prescribed three or more hypnotic drugs who visited neuropsychiatric outpatient clinics multiple times between April 2013 and March 2019. RESULTS: The frequency of prescribing three or more hypnotic drugs was six to nine times higher in psychiatry than in other departments. Flunitrazepam and brotizolam were the most common drugs prescribed and had the second lowest discontinuation rate after zolpidem. Conversely, eszopiclone, zopiclone, and suvorexant had the highest discontinuation rates. The success factors for drug reduction were age (odds ratio [OR]: 0.97, p < 0.0037), trazodone addition (OR: 12.86, p < 0.0194) and number of years of psychiatric experience. CONCLUSIONS: The characteristics and success factors in relation to drug reduction in patients with multiple prescriptions of hypnotic drugs identified in this study may contribute to solving the problem of multiple prescriptions of hypnotic drugs.

Altered Functional Connectivity during Mild Transient Respiratory Impairment Induced by a Resistive Load.

Background: Previous neuroimaging studies have identified brain regions related to respiratory motor control and perception. However, little is known about the resting-state functional connectivity (FC) associated with respiratory impairment. We aimed to determine the FC involved in mild respiratory impairment without altering transcutaneous oxygen saturation. Methods: We obtained resting-state functional magnetic resonance imaging data from 36 healthy volunteers during normal respiration and mild respiratory impairment induced by resistive load (effort breathing). ROI-to-ROI and seed-to-voxel analyses were performed using Statistical Parametric Mapping 12 and the CONN toolbox. Results: Compared to normal respiration, effort breathing activated FCs within and between the sensory perceptual area (postcentral gyrus, anterior insular cortex (AInsula), and anterior cingulate cortex) and visual cortex (the visual occipital, occipital pole (OP), and occipital fusiform gyrus). Graph theoretical analysis showed strong centrality in the visual cortex. A significant positive correlation was observed between the dyspnoea score (modified Borg scale) and FC between the left AInsula and right OP. Conclusions: These results suggested that the FCs within the respiratory sensory area via the network hub may be neural mechanisms underlying effort breathing and modified Borg scale scores. These findings may provide new insights into the visual networks that contribute to mild respiratory impairments.

Efficacy and Safety of Transitioning to Lemborexant from Z-drug, Suvorexant, and Ramelteon in Japanese Insomnia Patients: An Open-label, Multicenter Study.

INTRODUCTION: For patients with chronic insomnia, conventional therapy may not always provide satisfactory efficacy and safety. Thus, switching to an alternative therapeutic agent can be explored. However, there is a lack of prospective studies evaluating the effectiveness of such changes. This prospective, non-randomized, open-label, interventional, multicenter study assessed whether Japanese patients with chronic insomnia dissatisfied with treatment could transition directly to lemborexant (LEM) from four cohorts-non-benzodiazepine sedative-hypnotic (zolpidem, zopiclone, or eszopiclone) monotherapy, dual orexin receptor antagonist (suvorexant) monotherapy, suvorexant + benzodiazepine receptor agonists (BZRAs), and melatonin receptor agonist (ramelteon) combination. We evaluated whether transitioning to LEM improved patient satisfaction based on efficacy and safety. METHODS: The primary endpoint was the proportion of successful transitions to LEM at 2 weeks (titration phase end), defined as the proportion of patients on LEM by the end of the 2-week titration phase who were willing to continue on LEM during the maintenance phase (Weeks 2-14). Patient satisfaction and safety (the incidence of treatment-emergent adverse events [TEAEs]) were assessed at 14 weeks (end of titration and maintenance phases). RESULTS: Among the 90 patients enrolled, 95.6% (95% confidence interval: 89.0-98.8%) successfully transitioned to LEM at 2 weeks. The proportions of patients who successfully continued on LEM were 97.8% and 82.2% at the end of the titration and maintenance phases (Weeks 2 and 14), respectively. The overall incidence of TEAEs was 47.8%; no serious TEAEs occurred. In all cohorts, the proportions of patients with positive responses were higher than the proportions with negative responses on the three scales of the Patient Global Impression-Insomnia version. During the maintenance phase, Insomnia Severity Index scores generally improved at Weeks 2, 6, and 14 of LEM transition. CONCLUSIONS: Direct transition to LEM may be a valid treatment option for patients with insomnia who are dissatisfied with current treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04742699.

Positive association between the plasma levels of 5-hydroxyindoleacetic acid and the severity of depression in patients with chronic obstructive pulmonary disease.

BACKGROUND: The role of plasma monoamines in patients with chronic obstructive pulmonary disease (COPD) with depression is unclear. To investigate monoamines in 20 depressed patients with COPD, the plasma concentrations of serotonin, 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured and compared with those in 50 non-depressed COPD patients, and also with 23 age- and gender-matched non-smokers and 13 smokers as non-depressed healthy controls. METHODS: Diagnosis of depression was assessed using the Centre for Epidemiologic Studies Depression Scale. Plasma concentrations of monoamines were measured by high-performance liquid chromatography. RESULTS: None of the depressed COPD patients had suicidal ideation. The plasma 5-HIAA level [median, (25% and 75% quartiles)] in depressed COPD patients [6.8 ng/mL, (4.9 and 13.1)] was significantly higher than in non-depressed COPD patients [5.4, (4.2 and 7.5)] (p=0.022) and non-smokers [5.1 (3.8 and 7.2)] (p=0.041), but not smokers [4.7, (4.0 and 6.7)] (p>0.05). The plasma 5-HIAA level (r=0.24, p=0.049) was significantly associated with the severity of depression in patients with COPD. The plasma MHPG level was significantly higher in depressed COPD patients (p=0.043) than in smokers, but was not higher than that in non-depressed COPD patients or non-smokers, although the level of MHPG was not associated with the severity of depression. CONCLUSION: The plasma 5-HIAA level is increased in depressed COPD patients. Plasma monoamines may be a good biomarker for detection of depression in patients with COPD.

Low-molecular-weight adiponectin is more closely associated with episodes of asthma than high-molecular-weight adiponectin.

Adiponectin is divided into high-molecular-weight (HMW), middle-molecular-weight (MMW) and low-molecular-weight (LMW) types. While HMW adiponectin has been studied by many researchers, the roles of MMW and LMW adiponectin have not yet been sufficiently elucidated. In addition, there are conflicting findings regarding the role of adiponectin in chronic inflammatory diseases, especially asthma. Therefore, we compared patients who suffered episodes of asthma in the past (=asthmatics) with those who did not (=non-asthmatics) in order to investigate the relationship between asthma and HMW, MMW and LMW adiponectin. The subjects in this study included 76 university students. None of the subjects were smokers, on regular medications or seeing a doctor regularly at the time. Fourteen subjects reported past histories of asthma. We also measured and compared the levels of leptin and ghrelin to that of adiponectin, as these hormones are connected with inflammatory conditions. Although the physical data of the asthmatics were similar to those of the non-asthmatics, the levels of ghrelin and all fractions of adiponectin tended to be lower in the asthmatics than in the non-asthmatics. While the levels of MMW and LMW adiponectin in the asthmatics were found to be significantly low, the levels of ghrelin and HMW adiponectin were not clear. According to a multivariate regression analysis of the MMW and LMW adiponectin levels, asthma was found to be more significantly associated with the LMW adiponectin level than age, waist circumference or HDL-C. The results suggest that LMW adiponectin may be associated with episodes of asthma in males.

Memantine-associated hyperkalaemia in a patient with Alzheimer's disease.

Memantine is an N-methyl-D-aspartate glutamate receptor antagonist that may improve cognitive functions in patients with Alzheimer's disease. It is predominantly excreted unchanged via the kidneys, and patients with decreased creatinine clearance must be treated with lower doses of memantine. However, it is unclear whether memantine itself can lead to renal dysfunction and/or hyperkalaemia. We report a patient with renal impairment and hyperkalaemia possibly associated with memantine administration.

[Characteristics of single event-related cerebral hemodynamics during verbal task in emotionally charged state measured by multi-channel near-infrared spectroscopy (NIRS) in patients with schizophrenia: comparison with healthy subjects].

Neared infrared spectroscopy (NIRS) is one of the recently developed methodologies which can measure cerebral blood volumes to determine the blood hemoglobin (Hb) concentration simultaneously at multiple points with marked time resolution. Monitoring the changes in the Hb concentration yields site-specific readings on blood flow and, thus, on neural activities. The aim of this study was to examine the characteristics of a single event-related oxyhemoglobin concentration [oxy-Hb] changes in patients with schizophrenia using multi-channel NIRS during a word generation task, Japanese 'Shiritori', and single-word generation task in an emotionally charged state induced by three facial expressions of "crying", "neutral", and "smiling" babies' photographs. Thirty-four patients with schizophrenia and 34 age-matched healthy controls participated in the present study after giving consent. In healthy controls, [oxy-Hb] changes when viewing the "crying" baby's photograph were significantly larger than when viewing the "smiling" baby's photograph. On the other hand, in patients with schizophrenia, [oxy-Hb] changes when viewing the "smiling" baby's photograph were significantly larger than when viewing the "crying" baby's photograph. These results suggest that cautions/execution functions in patients with schizophrenia during the single event word "Shiritori" task measured by multi-channel NIRS were impaired. It was also suggested that, in patients with schizophrenia, the affective reaction influenced by each photograph may be different from healthy controls (mismatch). Multi-channel NIRS can be a useful tool for research and clinical purposes in psychiatry.