Real-world effectiveness of antipsychotic treatments in 1011 acutely hospitalized patients with schizophrenia: A one-year follow-up study.

PURPOSE: To compare the real-world effectiveness of antipsychotic treatments focusing on long-acting injectable antipsychotic medications (LAIs) and antipsychotic polytherapies except polytherapy involving clozapine (APEC) for patients with schizophrenia. METHODS: This prospective study was conducted over a 19-month period in 12 psychiatric emergency hospitals in Japan. Patients who were newly admitted to psychiatric emergency wards between September 2019 and March 2020 because of acute onset or exacerbation of Schizophrenia and Other Psychotic Disorders as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, were included. All patients were followed for one-year after discharge or until March 31, 2021. The primary outcome was the risk of treatment failure defined as psychiatric rehospitalization, discontinuation of medication, death, or continuation of hospitalization for one year. Cox proportional hazards multivariate regression was used for analyses. RESULTS: A total of 1011 patients were enrolled (women, 53.7%; mean [SD] age, 47.5 [14.8] years). During follow-up, 588 patients (58.2%) experienced treatment failure including rehospitalization (513 patients), discontinuation of medication (17 patients), death (11 patients), and continuation of hospitalization for one-year (47 patients). Switching to LAIs (hazard ratio [HR] 0.810, 95%CI 0.659-0.996) and APEC (HR 0.829, 95%CI 0.695-0.990) were significantly associated with a low rate of treatment failure. CONCLUSIONS: Switching to LAIs and APEC in early non-responders seems to be beneficial for the prevention of treatment failure in acutely admitted patients with schizophrenia. The risk of treatment failure was about 19% and 17% lower in patients treated with LAIs and APEC, respectively, than in patients treated without them.

Real-world effectiveness of antipsychotic monotherapy and polytherapy in 1543 patients with acute-phase schizophrenia.

PURPOSE: The effectiveness of antipsychotic treatments in the acute phase of schizophrenia in actual clinical practice remains somewhat unclear. Therefore, the purpose of the present naturalistic, multi-center study conducted from 1 year starting in September 2017 was to examine the response rate to an initial or second antipsychotic in newly admitted patients with acute-phase schizophrenia, as well as the response rate and quality of augmentation with two antipsychotics in patients who failed to respond to both the initial and second antipsychotics. RESULTS: In total, there were 660 (42.8%) and 243 (15.7%) responders to an initial and a second antipsychotic, respectively; thus, 58.5% of all patients were responders to an initial or second antipsychotic. Among 581 nonresponders (37.7%), the initial antipsychotic or a third antipsychotic was added to the second antipsychotic. Among these patients, 89.8% showed a Clinical Global Impression-Improvement score ≤3 (from 'minimally improved' to 'very much improved'). The rates of adverse events such as hyperglycemia, hyper-low-density lipoprotein cholesterolemia, hypertriglyceridemia, hyperprolactinemia, QTc prolongation, and extrapyramidal symptoms were not high in patients receiving augmentation with two antipsychotics compared with all patients, and no serious adverse events were reported. CONCLUSION: Antipsychotic augmentation may be an option in acute-phase treatment for patients who do not respond to either an initial or a second antipsychotic.

Feasibility and efficacy of shared decision making for first-admission schizophrenia: a randomized clinical trial.

BACKGROUND: The feasibility of shared decision making (SDM) for patients with schizophrenia remains controversial due to the assumed inability of patients to cooperate in treatment decision making. This study evaluated the feasibility and efficacy of SDM in patients upon first admission for schizophrenia. METHODS: This was a randomized, parallel-group, two-arm, open-label, single-center study conducted in an acute psychiatric ward of Numazu Chuo Hospital, Japan. Patients with the diagnosis of schizophrenia upon their first admission were randomized into a SDM intervention group or a usual treatment group in a 1:1 ratio. The primary outcome was patient satisfaction at discharge. The secondary outcomes were attitudes toward medication at discharge and treatment continuation at 6 months after discharge. RESULTS: Twenty-four patients were randomly assigned. The trial was prematurely terminated due to slow enrollment. At discharge, the mean score on satisfaction was 23.7 in the SDM group and 22.1 in the usual care group (unadjusted mean difference: 1.6; 95% CI: -5.2 to 2.0). Group differences were not observed in attitude toward medication and treatment continuation. There was no statistically significant difference between the groups for the mean Global Assessment of Functioning score at discharge or length of stay as safety endpoint. CONCLUSIONS: No statistical differences were found between the SDM group and usual care group in the efficacy outcomes and safety endpoints. Large trials are needed to confirm the efficacy of the SDM program upon first admission for schizophrenia. TRIAL REGISTRATION: The study has been registered with ClinicalTrials.gov as NCT01869660 (registered 27 May, 2013).

Efficacy of shared decision making on treatment satisfaction for patients with first-admission schizophrenia: study protocol for a randomised controlled trial.

BACKGROUND: Shared decision making is a promising model for patient-centred medicine, resulting in better clinical outcomes overall. In the mental health field, interventions that consider the patient-centred perspective--such as patient quality of life, involvement in the treatment, treatment satisfaction, and working alliance--have increased and better clinical outcomes discovered for patients with schizophrenia. However, few studies have examined the efficacy of shared decision making for schizophrenia treatment. The objective of this study is to evaluate the effect of a shared decision making intervention compared to treatment as usual on patient satisfaction at discharge for first-admission patients with schizophrenia. METHODS/DESIGN: This is a randomised, parallel-group, two-arm, open-label, single-centre study currently being conducted in an acute psychiatric ward of Numazu Chuo Hospital, Japan. We are recruiting patients between 16 and 65 years old who are admitted to the ward with a diagnosis of schizophrenia without prior experience of psychiatric admission. Fifty-eight participants are being randomised into a shared decision making intervention group or a treatment as usual control group in a 1:1 ratio. The intervention program was developed based on a shared decision making model and is presented as a weekly course lasting the duration of the patients' acute psychiatric ward stay. The primary outcome measure is patient satisfaction at discharge as assessed by the Client Satisfaction Questionnaire. Due to the study's nature, neither the patient nor staff can be blinded. DISCUSSION: This is the first randomised controlled trial to evaluate the efficacy of shared decision making for patients with early-treatment-stage schizophrenia. The intervention program in this study is innovative in that it includes both of the patient and staff who are involved in the treatment. TRIAL REGISTRATION: The study has been registered with ClinicalTrials.gov as NCT01869660.

Characteristics of suicide attempters with family history of suicide attempt: a retrospective chart review.

BACKGROUND: Family history of suicide attempt is one of the risks of suicide. We aimed at exploring the characteristics of Japanese suicide attempters with and without a family history of suicide attempt. METHODS: Suicide attempters admitted to an urban emergency department from 2003 to 2008 were interviewed by two attending psychiatrists on items concerning family history of suicide attempt and other sociodemographic and clinical information. Subjects were divided into two groups based on the presence or absence of a family history of suicide attempt, and differences between the two groups were subsequently analyzed. RESULTS: Out of the 469 suicide attempters, 70 (14.9%) had a family history of suicide attempt. A significantly higher rate of suicide motive connected with family relations (odds ratio 2.21, confidence interval 1.18-4.17, p < .05) as well as a significantly higher rate of deliberate self-harm (odds ratio 2.51, confidence interval 1.38-4.57, p < .05) were observed in patients with a family history of suicide compared to those without such history. No significant differences were observed in other items investigated. CONCLUSION: The present study has revealed the characteristics of suicide attempters with a family history of suicide attempt. Further understanding of the situation of such individuals is expected to lead to better treatment provision and outcomes, and family function might be a suitable focus in their treatment.

Dopamine D2 receptor gene polymorphisms are associated with suicide attempt in the Japanese population.

BACKGROUND: Some reports have suggested the involvement of the D2 dopaminergic function in the expression of suicidal behavior. Here, we examined associations between suicide attempts and two kinds of functional polymorphisms in the dopamine D2 receptor (DRD2) gene, namely, TaqIA and -141C Ins/Del. METHODS: Subjects included 120 suicide attempters and 123 unrelated volunteers. Those who attempted suicide were severely injured and were transferred to the emergency unit in our university hospital. To determine each genotype, we performed polymerase chain reaction and restriction fragment length polymorphism analyses. RESULTS: We found significant differences in genotypic and allelic frequencies of -141C Ins/Del and TaqIA polymorphisms between suicide attempters and healthy controls (-141C Ins/Del, p = 0.01; TaqIA,p = 0.036). The Ins allele of -141C Ins/Del was significantly more frequent in suicide attempters (p = 0.011), as well as the A2 allele of TaqIA (p = 0.017). Haplotype analysis revealed no significant linkage disequilibrium between -141C Ins/Del and TaqIA polymorphisms (D' = 0.226, r(2) = 0.016, p = 0.10). CONCLUSIONS: These findings suggest that DRD2 gene polymorphisms may be involved in the biological susceptibility to suicide.

Trait aggression in suicide attempters: a pilot study.

Suicide attempt is a potent risk factor of subsequent suicide. Understanding the characteristics of suicide attempters is important for preventing suicide. The authors investigated aggression in medically serious suicide attempters at an emergency department. Trait aggression was evaluated in 55 suicide attempters and 71 healthy individuals as a control group using the Japanese version of the Buss-Perry Aggression Questionnaire (BAQ). Total BAQ scores (t = 2.782, P = 0.006) and the hostility scores (t = 3.735, P < 0.001) were significantly higher in the suicide attempters than the controls. It suggested that to focus on aggression and its management is one of the key components for preventing suicide.

Psychiatric assessment of suicide attempters in Japan: a pilot study at a critical emergency unit in an urban area.

BACKGROUND: The incidence of suicide has increased markedly in Japan since 1998. As psychological autopsy is not generally accepted in Japan, surveys of suicide attempts, an established risk factor of suicide, are highly regarded. We have carried out this study to gain insight into the psychiatric aspects of those attempting suicide in Japan. METHODS: Three hundred and twenty consecutive cases of attempted suicide who were admitted to an urban emergency department were interviewed, with the focus on psychosocial background and DSM-IV diagnosis. Moreover, they were divided into two groups according to the method of attempted suicide in terms of lethality, and the two groups were compared. RESULTS: Ninety-five percent of patients received a psychiatric diagnosis: 81% of subjects met the criteria for an axis I disorder. The most frequent diagnosis was mood disorder. The mean age was higher and living alone more common in the high-lethality group. Middle-aged men tended to have a higher prevalence of mood disorders. CONCLUSION: This is the first large-scale study of cases of attempted suicide since the dramatic increase in suicides began in Japan. The identification and introduction of treatments for psychiatric disorders at emergency departments has been indicated to be important in suicide prevention.

Knowledge and attitude towards suicide among medical students in Japan: preliminary study.

Japan has one of the highest suicide rates in the world. Suicides numbered 32,863 in 1998 and have exceeded 30,000 in every subsequent year. Education of those involved in general and psychosocial patient care can contribute greatly to suicide prevention. The authors administered a brief knowledge and attitude assessment questionnaire concerning suicide to students in their first, third, and fifth years at a Japanese medical school. Participants numbered 160 (94 men with a mean age of 21.8 years, SD = 3.01, and 66 women with a mean age of 21.2 years, SD = 2.64); 59 first year, 52 third year, and 49 in their fifth year. The questionnaire consists of eight multiple-choice questions asking knowledge of suicide and one open-ended question asking attitude. In the knowledge part, only about half of the items were answered correctly (mean score was 4.21, SD = 1.28). A significant difference was observed in prevalence of attitudes as categorical variables between student years (P = 0.001). Sympathetic comments increased along with student years, while critical comments decreased. Given the frequent and interventional opportunities of primary-care medical contacts, poor understanding of suicide from the medical viewpoint was of concern. Moreover, judgmental attitudes were common, especially in earlier school years. Better informed, more understanding physicians and other health professionals could contribute greatly to prevention.

CYP2D6 gene deletion allele in patients with neuroleptic malignant syndrome: preliminary report.

Neuroleptic malignant syndrome (NMS) is a potentially fatal adverse reaction to psychopharmacologic treatment. Reported herein are two NMS patients with schizophrenia who were found to possess a CYP2D6 gene deletion allele (CYP2D6*5). The deletion results in decreased CYP2D6 activity, possibly leading to drug accumulation. Both patients with NMS had been treated with neuroleptics, including CYP2D6 substrates. Polymerase chain reaction (PCR) followed by restriction fragment length polymorphism analyses and long PCR were performed to detect CYP2D6 genotype. One patient was found to possess *5/*10; the other had a *1/*5 genotype. The present preliminary report suggests that pharmacokinetic factors cannot be excluded and the CYP2D6 polymorphism is possibly associated with the etiology of NMS.

Characterization of the interaction of a recombinant soluble neuroligin-1 with neurexin-1beta.

Neuroligins, proteins of the alpha/beta-hydrolase fold family, are found as postsynaptic transmembrane proteins whose extracellular domain associates with presynaptic partners, proteins of the neurexin family. To characterize the molecular basis of neuroligin interaction with neurexin-beta, we expressed five soluble and exportable forms of neuroligin-1 from recombinant DNA sources, by truncating the protein before the transmembrane span near its carboxyl terminus. The extracellular domain of functional neuroligin-1 associates as a dimer when analyzed by sedimentation equilibrium. By surface plasmon resonance, we established that soluble neuroligins-1 bind neurexin-1beta, but the homologous alpha/beta-hydrolase fold protein, acetylcholinesterase, failed to associate with the neurexins. Neuroligin-1 has a unique N-linked glycosylation pattern in the neuroligin family, and glycosylation and its processing modify neuroligin activity. Incomplete processing of the protein and enzymatic removal of the oligosaccharides chain or the terminal sialic acids from neuroligin-1 enhance its activity, whereas deglycosylation of neurexin-1beta did not alter its association capacity. In particular, the N-linked glycosylation at position 303 appears to be a major determinant in modifying the association with neurexin-1beta. We show here that glycosylation processing of neuroligin, in addition to mRNA splicing and gene selection, contributes to the specificity of the neurexin-beta/neuroligin-1 association.

Lack of association in Japanese patients between neuroleptic malignant syndrome and the TaqI A polymorphism of the dopamine D2 receptor gene.

OBJECTIVE: The molecular basis of neuroleptic malignant syndrome (NMS) is unclear, but clinical studies have noted a genetic predisposition. A recent genetic study suggested an association between NMS and the I A polymorphism in the dopamine D2 receptor (DRD2 ) gene. We further examined the association in a larger number of subjects. METHODS: We studied 49 Japanese patients previously diagnosed with NMS, and 123 schizophrenic patients treated with neuroleptics without occurrence of NMS. PCR and RFLP analyses were performed to screen the I A polymorphism. RESULTS: The I A1 allele frequency was 0.408 in NMS patients and 0.415 in patients without NMS. No significant differences in allelic or genotypic frequencies were observed between the two groups. CONCLUSIONS: We cannot conclude that the I A polymorphism is associated with development of NMS.