Effects of titration speed, gender, obesity and concomitant medications on the risk and onset time of clozapine-associated fever among Japanese patients with schizophrenia: retrospective review of charts from 21 hospitals.

BACKGROUND: Clozapine-induced inflammation, such as myocarditis and pneumonia, can occur during initial titration and can be fatal. Fever is often the first sign of severe inflammation, and early detection and prevention are essential. Few studies have investigated the effects of clozapine titration speed and concomitant medication use on the risk of clozapine-induced inflammation. AIMS: We evaluated the risk factors for clozapine-associated fever, including titration speed, concomitant medication use, gender and obesity, and their impact on the risk of fever and the fever onset date. METHOD: We conducted a case-control study. The medical records of 539 Japanese participants with treatment-resistant schizophrenia at 21 hospitals in Japan who received clozapine for the first time between 2010 and 2022 were retrospectively investigated. Of these, 512 individuals were included in the analysis. Individuals were divided into three groups according to the titration rate recommended by international guidelines for East Asians: the faster titration group, the slower titration group and the ultra-slower titration group. The use of concomitant medications (such as antipsychotics, mood stabilisers, hypnotics and anxiolytics) at clozapine initiation was comprehensively investigated. Logistic regression analysis was performed to identify the explanatory variables for the risk of a fever of 37.5°C or higher lasting at least 2 days. RESULTS: Fever risk significantly increased with faster titration, male gender and concomitant use of valproic acid or quetiapine. No increased fever risk was detected with the use of other concomitant drugs, such as olanzapine, lithium or orexin receptor antagonists. Fever onset occurred significantly earlier with faster titration. Multivariate analysis identified obesity as being a factor that accelerated fever onset. CONCLUSION: A faster titration speed and concomitant treatment with valproic acid and quetiapine at clozapine initiation increased the risk of clozapine-associated fever. Clinicians should titrate clozapine with caution and consider both the titration speed and concomitant medications.

Patients with diabetes and obesity exhibit characteristics in eating and coping behaviors and personality traits.

Aims/introduction: In patients with diabetes, obesity is an aggravating factor for glycemic control and its vascular complications. However, the psychological and behavioral characteristics of those patients with obesity have not been fully clarified. This study investigated eating and coping behavior, personality traits, quality of life (QOL), and depression status in patients with diabetes with or without obesity. Materials and methods: Questionnaires obtained from 567 patients with diabetes at Dokkyo Medical University were analyzed. Eating behavior, coping behavior, personality traits, QOL, and depression status were evaluated by the Eating Behavior Questionnaire, Brief COPE, Japanese Ten-Item Personality Inventory, EuroQol 5 Dimensions-5 Level, and Patient Health Questionnaire-9, respectively. Participants were divided according to body mass index (BMI) into a non-obese group (BMI < 25), obese group (BMI 25-35), and high-degree obese group (BMI ≥ 35), and results were compared between groups. Results: On all items of the Eating Behavior Questionnaire, scores were higher in the obese and high-degree obese groups than non-obese group, indicating worse eating behavior. In coping behavior, significant intergroup differences were found in self-distraction, substance use, using emotional support, using instrumental support, and venting. As for personality traits, the obese group had significantly lower conscientiousness and higher emotional instability than the non-obese group. There was no significant difference in QOL or depression status. Conclusions: These results suggest that there are some characteristics in eating and coping behaviors and some personality traits between obese and non-obese patients with diabetes. Treatment based on such characteristics may be useful for patients with diabetes and obesity. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-024-00721-w.

Effect of concomitant use of yokukansan on steady-state blood concentrations of donepezil and risperidone in real-world clinical practice.

AIM: Yokukansan is one of the most frequently used herbal medicines that can improve the behavioral and psychological symptoms of dementia. In this exploratory study, we investigated whether yokukansan affects the steady-state blood concentrations of donepezil, risperidone, and the major metabolites of both drugs in a real-world clinical setting. METHODS: A non-randomized, open-label, single-arm study examining drug-drug interactions was conducted. Fifteen dementia patients taking donepezil for at least 4 weeks and eight schizophrenia patients taking risperidone for at least 2 weeks were orally administered 2.5 g of yokukansan three times a day before or between meals, and blood samples were collected before and 8 weeks after starting co-treatment with yokukansan. Plasma concentrations of donepezil, risperidone, and each metabolite were measured using high-performance liquid chromatography-tandem mass spectrometry and compared before and after the 8-week administration of yokukansan. RESULTS: The plasma concentrations of donepezil and its metabolites (6-O-desmethyl-donepezil, 5-O-desmethyl-donepezil, and donepezil-N-oxide), risperidone, and its metabolite paliperidone did not differ before and after the 8-week treatment with yokukansan. CONCLUSIONS: The findings of this study show that the concomitant use of yokukansan may have little clinical impact on the steady-state blood levels of donepezil and risperidone in patients with dementia or schizophrenia.

Real-world predictors of changes in fear of COVID-19 in the Japanese general population: a large-scale internet-based cohort study with 20,712 participants.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a respiratory infection that considerably impacts both physical and mental health. In particular, the prolonged nature of psychological issues associated with COVID-19 has become a concern. However, evidence based on longitudinal studies investigating the changes in fear of COVID-19 has been limited, posing a public health challenge. METHODS: We investigated the predictors of changes in the Fear of COVID-19 Scale (FCV-19S) scores in the general Japanese population using data from a large-scale internet-based cohort study. RESULTS: We included 20,712 study participants (mean age = 51.1 years, percentage of males = 49.9%). The baseline FCV-19S score for the research participants was 17.0, and one year later, the FCV-19S score decreased to 15.8. The predictors of increase in FCV-19S scores were older age, male sex, COVID-19 requiring oxygen therapy, higher baseline FCV-19S total score, severe psychological distress, never married, worsening subjective health status, a greater number of COVID-19 vaccinations, a history of alcohol dependency, and living with family members. Conversely, the predictors of decrease in FCV-19S scores included habitual alcohol intake, COVID-19 not requiring oxygen therapy and a higher household income. Our study was an internet-based survey focused on residents of Japan, which raises the possibility of selection bias and makes it unclear whether the findings can be extrapolated to other countries and cultures. CONCLUSION: During the observation period, the FCV-19S scores significantly decreased. Severe COVID-19 requiring oxygen therapy within one year of baseline was the most impactful predictor of an increase in FCV-19S score. On the other hand, mild COVID-19 not requiring oxygen therapy was a predictor of a decrease in FCV-19S scores. Therefore, we believe that it is necessary to adopt individualized approaches stratified by the severity of the infection when addressing the fear of COVID-19.

Predictors of somatic symptoms during the COVID-19 pandemic: a national longitudinal survey in Japan.

OBJECTIVES: The COVID-19 pandemic has highlighted the long-term consequences of SARS-CoV-2 infection, termed long COVID. However, in the absence of comparative groups, the differentiation of disease progression remains difficult, as COVID-19 symptoms become indistinguishable from symptoms originating from alternative etiologies. This study aimed to longitudinally investigate the association between COVID-19 exposure and the somatic symptoms in the Japanese general population. DESIGN: This was a longitudinal cohort study with 1-year follow-up. SETTING AND PARTICIPANTS: Longitudinal data from 19 545 individuals who participated in the Japan Society and New Tobacco Internet Survey (JASTIS) 2022 and 2023 were included. In this study, we used data from the 2022 JASTIS as baseline data and the 2023 JASTIS as follow-up data. Based on questionnaire responses, respondents were classified into three categories of exposure to COVID-19. OUTCOME MEASURES: The somatic symptoms were assessed by the Somatic Symptom Scale-8 (SSS-8). Using generalised linear models adjusted for baseline covariates, we calculated the ORs of having very high somatic symptoms assessed by SSS-8, attributable to COVID-19 exposure (no COVID-19 cases as the reference group). RESULTS: Follow-up completers were divided into three groups according to COVID-19 exposure (no COVID-19, n=16 012; COVID-19 without O2 therapy, n=3201; COVID-19 with O2 therapy, n=332). After adjusting for all covariates, COVID-19 cases with O2 therapy had a significant positive association (OR 7.60, 95% CI 5.47 to 10.58) with a very high somatic symptoms burden while other COVID-19 exposure groups did not. Pre-existing physical and psychological conditions were also associated with increased risk of somatic symptoms. CONCLUSION: The findings of our study suggest that the severity of COVID-19 symptoms requiring O2 therapy in the acute phase led to high somatic symptoms. Pre-existing conditions were also associated with a subsequent risk of somatic symptoms.

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

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

Continuous alcohol withdrawal delirium and physical illness-associated delirium in a man brought to the emergency department after a disaster: A case report.

BACKGROUND: Risk factors for alcohol withdrawal delirium include heavy drinking, prior alcohol withdrawal delirium or convulsions, nondrug sedative use, and a history of tachycardia, withdrawal, and infections. CASE PRESENTATION: A 76-year-old man with a history of heavy drinking and type 2 diabetes was hospitalized for hypothermia, rhabdomyolysis, and acute renal failure after a typhoon. He developed alcohol withdrawal symptoms 24 h after his last drink, leading to severe withdrawal delirium characterized by restlessness, delusions, and altered consciousness. Treatment included lorazepam, in addition to comprehensive care for his physical condition. His condition fluctuated, especially at night, with his psychiatric symptoms exacerbated by his physical illnesses, suggesting delirium due to the coexistence of severe and multiple physical illnesses. After 44 days, following substantial improvements in both mental and physical health with perospirone, the patient was discharged. CONCLUSION: This case emphasizes the need for multidisciplinary collaboration in the treatment of such patients, especially during disasters, and the importance of long-term monitoring for elderly patients with alcohol dependence syndrome after a disaster.

Vortioxetine-induced syndrome of inappropriate secretion of antidiuretic hormone: A case report.

BACKGROUND: Vortioxetine, known for its efficacy in treating depression through its effects on various neurotransmitters, has not been previously reported to induce syndrome of inappropriate secretion of antidiuretic hormone (SIADH). CASE PRESENTATION: This case report describes a 74-year-old man with major depressive disorder who developed SIADH 1 week after starting treatment with vortioxetine. SIADH is characterized by symptoms such as headache, nausea, disorientation, and seizures, stemming from hyponatremia (123 mEq/L), without dehydration or edema. Vortioxetine was discontinued, and an alternative drug, mianserin, was initiated. The patient was restricted from drinking water due to hyponatremia. The serum Na concentration improved over time to within the normal range by the second week after admission. CONCLUSION: This is the first case report of vortioxetine-induced SIADH.

Changes in suicidal ideation during treatment among patients with major depressive disorder: A 6-month naturalistic follow-up study.

AIM: There is limited evidence regarding predictors of changes in suicidal ideation (SI) in patients with major depressive disorder (MDD). The objective of this study was to describe changes in SI over a 6-month period and identify their predictors from naturalistic observations of MDD patients. METHODS: In the cross-sectional analysis, we examined 257 patients with MDD at the first-visit assessment. Among the patients, 119 who completed the 6-month assessment (completers) were included in the longitudinal analysis. For the evaluation of depressive symptoms, including SI, the Quick Inventory of Depressive Symptomatology-Japanese version was administered at both the first-visit and follow-up assessments. At baseline, we also administered the Japanese version of the Ten Item Personality Inventory to assess personality traits and the PRIME Screen-Revised to assess psychotic symptoms. RESULTS: In the cross-sectional analysis of first-visit patients, 36.2% (93/257) exhibited SI. Among completers, 14.3% (17/119) had prolonged SI. Among the completers with SI at the first-visit assessment, 38.6% (17/44) had SI at the follow-up assessment (prolonged SI). In linear regression models including all completers, prolonged SI was positively associated with endorsement of suspiciousness/persecutory ideas and negatively associated with higher age. CONCLUSION: More than one-third of completers who had SI at the first-visit assessment experienced prolonged SI (SI at follow-up). Our findings can help clinicians predict the course of MDD by identifying associated demographic and clinical characteristics.

Predictors of the intentions to leave among nurses in an academic medical center.

Aim: Nurses are an essential human resource for the healthcare system. However, high turnover of nurses is a current issue. Reducing the high turnover of nurses is crucial for facilitating the sustainable provision of care in hospitals. The purpose of this study was to explore the factors affecting nurses' intentions to leave among nurses in an advanced medical center. Methods: Using a cross-sectional design, we conducted a questionnaire survey of nurses working at an academic medical center in August 2020. Of the 1063 distributed questionnaires, there were 821 (77.2%) valid responses. The questionnaire included items on the Kessler 6 (K6), New Brief Job Stress Questionnaire (New BJSQ), Organizational Justice Questionnaire (OJQ), and intention to leave a hospital job. Results: Overall, the mean age of the nurses was 34.3 ± 10.1 years and 87.8% (721/821) of them were female. Among respondents, 19.5% (160/821) had a strong intention to leave. After adjusting for all the variables, a logistic regression analysis revealed that longer working hours, job rank (staff nurse), work-self-balance positive (imbalance), workplace harassment (no bullying), and interactional justice (unfair supervisor) were determinants associated with strong intentions to leave. Conclusions: Approximately one-fifth of nurses working at advanced medical center had a strong intention to leave. However, our findings can help managers predict the turnover of nurses by understanding occupational characteristics. Managing work-self-balance and treating staff fairly could improve work environments. Further research focusing on the outcome of actual turnover rather than intention to leave is needed.

Factors associated with the work-self balance of nurses in an advanced medical center.

Aim: Balancing between personal and working life of nurses is important to increase their job satisfaction and to continue their careers. Our purpose was to investigate the relationship between nurses and work-self balance (WSB) at different phases of life, such as age, marriage and raising children, and the occupational factors that influence WSB that can be used to improve the work environment for nurses. Methods: Using a self-administered questionnaire, we asked about gender, age, marital status, presence of children, working hours, and night shift. Occupational stresses, including WSB, were assessed with the New Brief Job Stress Questionnaire (New BJSQ) and the Organizational Justice Questionnaire (OJQ). The total number of unmarried and married respondents was 819. We investigated whether marital status and cohabiting children make a difference in WSB in the three age groups (less than 30 years, 31-40 years, and more than 41 years) using a Mann-Whitney U test. In addition, we examined occupational factors affecting WSB using multiple regression analysis. Results: The value of WSB negative was significantly greater in the group of married persons than in the group of unmarried persons (p < 0.05) and was significantly greater in the group with cohabiting children than in the group without cohabiting children (p < 0.01) only in the group aged 31-40 years. Multiple regression analysis indicated that significant occupational factors affecting WSB differed by each age group. Conclusion: This survey showed that the factors and degree of WSB vary according to the generation and family environment of nurses.

Associations between the number of antipsychotics prescribed and metabolic parameters in Japanese patients with schizophrenia.

Aim: There is little evidence on the effects of antipsychotic polypharmacy on metabolic parameters in patients with schizophrenia. Thus, this cross-sectional study explored the associations between the number of antipsychotics prescribed and metabolic parameters in Japanese patients with schizophrenia. Methods: We obtained metabolic parameter data from 19,675 patients with schizophrenia. Of these, 1380 (7.0%), 8422 (42.8%), 6326 (32.2%), and 3547 (18.0%) were treated with none, one, two, and three or more antipsychotics, respectively. We compared eight metabolic parameters among the four groups using univariate analyses. We then performed multiple regression analysis to assess the effect of the number of antipsychotics prescribed on metabolic parameters after controlling for the effects of age, sex, type of care (outpatient/inpatient), chlorpromazine-equivalent dose, and antipsychotic type (aripiprazole, olanzapine, and risperidone). Results: There were significant differences in body mass index (BMI), systolic and diastolic blood pressure (dBP), total cholesterol, low-density lipoprotein cholesterol, and triglycerides among the four groups. The multiple regression analysis showed that the number of antipsychotics prescribed was significantly correlated with BMI and dBP (standardized regression coefficient = 0.031 and 0.026, respectively). Conclusion: Our results suggested that the number of antipsychotics prescribed adversely affects BMI and dBP. Clinicians should avoid inappropriate antipsychotic polypharmacy, especially polypharmacy involving three or more antipsychotics.