Combination of strategies to initiate clozapine for refractory schizophrenia in a patient with low neutrophil levels.

Clozapine is the only drug with confirmed efficacy for refractory schizophrenia; however, its use is restricted due to the risk of potentially life-threatening side effects, such as agranulocytosis. Although this restriction ensures safety against haematological risks, some patients with refractory schizophrenia who have low neutrophil levels may miss the opportunity to receive clozapine treatment. We herein report the case of a patient with refractory schizophrenia and low neutrophil levels who was successfully initiated on clozapine treatment after the use of several methods for increasing neutrophil levels. These strategies consisted of discontinuation of antipsychotics, treatment with lithium carbonate and adenine, and light exercise before blood testing. Combining these procedures may be an effective option in the treatment of patients with refractory schizophrenia whose neutrophil levels are not sufficient to initiate clozapine.

Pharmacological interventions for social cognitive impairments in schizophrenia: A protocol for a systematic review and network meta-analysis.

Background: Social cognitive impairments adversely affect social functioning (e.g., employment status) in patients with schizophrenia. Although pharmacological interventions have been suggested to provide some benefits on social cognition, little information is available on the comparative efficacy of pharmacotherapy. Thus, the aim of this planned systematic review and network meta-analysis is to perform a quantitative comparison of the effects of various psychotropic drugs, including supplements, on social cognition disturbances of schizophrenia. Methods: The literature search will be carried out using the PubMed, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, ClinicalTrials.gov, and International Clinical Trials Registry Platform databases from inception onward. Randomized controlled trials that examined the efficacy of drugs in social cognitive disturbances will be included, based on the most recent studies and the broader literature than previously searched. This protocol defines a priori the methods that will be used for study selection, data collection, quality assessment, and statistical syntheses. Discussion: The findings this work are expected to help promote the development of better therapeutics of social cognitive impairments in schizophrenia and related psychiatric conditions. Systematic Review Registration: [www.crd.york.ac.uk/prospero], identifier [CRD42021293224].

The Effectiveness of Self-Esteem-Related Interventions in Reducing Suicidal Behaviors: A Systematic Review and Meta-Analysis.

Suicide is a serious social issue and is often treated using psychological interventions. The current systematic review and meta-analysis aimed to investigate the effectiveness of self-esteem-related interventions on suicidal behaviors. A systematic literature search for randomized controlled trials (RCTs) including a self-esteem component was conducted on 29 May 2021 and updated on 4 April 2022. In total, 12 studies were included in the systematic review and five studies were included in the meta-analysis. Small effect sizes were found for suicidal ideation at post intervention [g = -0.24, 95% CI (-0.48, 0.00)] and a 3-month follow-up [g = -0.36, 95% CI (-0.62, -0.11)]. However, these results should be interpreted cautiously due to the limited number of included studies and varied sample population. In conclusion, the current review suggests that future intervention studies should incorporate self-esteem enhancement in the treatment of suicidal behaviors, especially for suicidal ideation. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=250882.

Predictors of social anxiety disorder with major depressive episodes among Japanese university students.

BACKGROUND: Social anxiety disorder (SAD) develops in the early teens and is a common disorder among university students. Understanding the predictive factors of SAD comorbid with major depressive episode (MDE) is important for student mental health care. The aim of this study was to identify the personality traits that predict SAD with MDE by analyzing longitudinal data of Japanese university students. METHODS: In this retrospective study, Japanese university students who visited the health care center of Hokkaido University for the first time were divided into the following four groups: "Control" (n = 43), "MDE" (n = 16), "SAD" (n = 28), and "SAD with MDE" (n = 61) based on the Patient Health Questionnaire-9 (PHQ-9), the Liebowitz Social Anxiety Scale, and core anxiety symptoms for SAD in the Mini International Neuropsychiatric Interview during screening. Predictors for SAD with MDE were identified by a four-group comparison of the Temperament and Character Inventory and PHQ-9 data previously obtained at the enrollment using analysis of variance and post-hoc tests. RESULTS: Upon comparing the four groups using analysis of variance, there were significant differences in the baseline PHQ-9 summary score, Harm-Avoidance (HA), and Self-Directedness (SD). According to results of the post-hoc test, all three showed a significant difference between the "Control" and "SAD with MDE." Furthermore, there was a significant difference in HA scores between "SAD" and "Control." In all the groups, the mean time from enrollment to the first visit to the center was >2 years. CONCLUSION: A higher HA score at baseline is a predictor of SAD with or without MDE. Higher PHQ-9 summary and lower SD scores at baseline are predictive factors of SAD with MDE.

Pulverizing medication as a harm reduction and intentional drug overdose prevention strategy: Two case studies.

AIMS: We explored the use of pulverized medication as a new method to prevent intentional drug overdose. METHODS: This case study presents data obtained from the medical records of two female patients, aged 19 and 27 years, who presented with schizophrenia and neurodevelopmental disorder, respectively. Both patients provided written informed consent. Medication was administered to the two patients in powdered form, as opposed to in tablet form, in an attempt to prevent intentional drug overdose. RESULTS: This administration method successfully prevented intentional drug overdose for 3 and 5 years in each case, respectively. However, case-control or prospective cohort studies are needed to rule out biases, including cognitive bias. CONCLUSION: Pulverizing medication is a simple and effective means of preventing intentional drug overdose by restricting access to the means of suicide, regardless of the type of mental disorder.

Character configuration, major depressive episodes, and suicide-related ideation among Japanese undergraduates.

AIM: To enable early identification of university students at high risk for suicide, we examined personality as a predictive factor for major depressive episodes and suicide-related ideation. METHODS: From 2011 to 2013, we administered the Patient Health Questionnaire-9 (PHQ-9) and the Temperament and Character Inventory (TCI) to 1,997 university students at enrollment (T1). We previously conducted a study using the same data set; this is a re-analysis of the dataset. To prevent contamination of data, participants diagnosed with a depressive episode were excluded at T1. Three years after enrollment (T2), we re-administered the PHQ-9 to the same students. We statistically compared TCI scores at T1 among depressive episode groups and suicide-related ideation groups. Two-way ANOVA and Cochran-Armitage trend tests were used to analyze the relationships between personality traits, depressive episodes, and suicide-related ideation. RESULTS: The PHQ-9 summary scores at baseline (T1) were 3.0 (±2.7), with female students scoring 4.6 (±2.9) and male students 2.9 (±2.6, p = 0.025). The major depressive episode group at T2 had lower self-directedness (SD) scores at T1 than the non-depressive episode control group. The suicide-related ideation (SI) group at T2 also had higher harm avoidance (HA), lower SD, and lower cooperativeness (C) scores than the non-SI group at T1. The Cochran-Armitage trend tests revealed significant associations between character configurations composed of SD and C, and both depressive episodes at T2 and SI at T2. CONCLUSION: The temperament feature of high HA at baseline and character configurations of low SD and low C at baseline are the most contributory predictors for the novel development of depressive episodes and SI among Japanese university students.

Pilot Validation Study of the Japanese Translation of the Brief Negative Symptoms Scale (BNSS).

PURPOSE: The brief negative symptoms scale (BNSS) is a concise instrument used to assess negative symptoms of subjects with schizophrenia covering five domains of negative symptoms and is suitable for use in clinical, experimental, and epidemiological settings. The original and translated version of BNSS has thus far been shown to have adequate psychometric properties. This study aimed to examine internal consistency, inter-rater and test-retest reliability, discriminant and convergent validity, and factor structure of the Japanese version of BNSS. PATIENTS AND METHODS: The assessment was performed by 11 raters using interview videos of nine subjects. Reliability was calculated with Cronbach's alpha for internal consistency and intra class correlation coefficient (ICC) for inter-rater reliability. Pearson's correlation coefficients were calculated to estimate the test-retest reliability. In addition to BNSS, Scale for assessment of negative symptoms (SANS) and scale for assessment of positive symptoms (SAPS) was obtained to assess the convergent and discriminant validity. Factor structure was assessed using principle factor analysis. RESULTS: The Japanese BNSS showed excellent internal consistency (Cronbach's alpha=0.95), inter-rater reliability (intra class correlation coefficient=0.97), and test-retest reliability (r=0.94, p<0.001). The convergent validity shown by correlation with SANS total score (r=0.87, p<0.001) and discriminant validity shown by correlation with SAPS total score (r=0.17, p=-0.68) were also good. Principal factor analysis revealed a two-factor structure of BNSS, although the loading of each item differed from that in the literature. CONCLUSION: Our pilot study demonstrated that Japanese BNSS had good psychometric properties which were achieved with relatively brief training. Further studies with more subjects and raters with various backgrounds recruited from multiple sites are warranted.

Prediction of major depressive episodes and suicide-related ideation over a 3-year interval among Japanese undergraduates.

BACKGROUND: Suicide has been a leading cause of death among young adult populations in Japan. The aim of this study was to predict major depressive episodes (MDEs) and suicide-related ideation among university students using the Patient Health Questionnaire-9 (PHQ-9) and the Temperament and Character Inventory (TCI). METHODS: The subjects were 2194 university students who completed the PHQ-9 and TCI in the 1st year (T1) and the PHQ-9 in the 4th year (T2) of university. Multiple logistic regression analysis was performed to predict MDEs and suicide-related ideation at T2. Moreover, recursive partitioning analyses were conducted to reveal the future risk of MDEs and suicide-related ideation. RESULTS: The multiple logistic regression analyses of MDEs and suicide-related ideation at T2 revealed that depressive episodes, suicide-related ideation, and low self-directedness(SD) scores at T1 were significant predictors. The area under the curve of the model for MDEs was 0.858 and that for suicide-related ideation was 0.741. The recursive partitioning analyses revealed that a PHQ-9 summary score ≥15 at T1 predicted a high risk of MDEs at T2 and that both a PHQ-9 summary score ≥5 and a PHQ-9 #9 score ≥1 predicted a high risk of suicide-related ideation at T2. CONCLUSIONS: MDEs, suicide-related ideation, and low SD scores are significant predictors of future MDEs and suicide-related ideation.

Hyperosmolar hyperglycemic state secondary to neuroleptic malignant syndrome.

Neuroleptic malignant syndrome (NMS) is often considered to be a precipitating factor for diabetic coma, such as a hyperosmolar hyperglycemic state (HHS). The combination of NMS and a systemic illness such as HHS can be difficult to diagnose because NMS may mask the coexisting condition. Although this coexistence is rare, it may be fatal if not detected early. We report a case of HHS in a 47-year-old male patient that developed after the distinguishing features of NMS had subsided. After the diagnosis of HHS, his recovery was a result of intravenous administration of soluble human insulin and fluid supplementation. Physicians caring for patients with diabetes who are also treated with neuroleptic agents should be aware that NMS may precipitate the development of secondary hyperglycemia despite a history of well-controlled blood glucose levels.