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The article discusses research which examined the effects of policy interventions on psychotropics polypharmacy among Japanese older adults. The study determined the proportion of patients prescribed with psychotropics, antidepressants, antipsychotics, hypnotics and anxiolytics. Study limitations include the use of the DeSC Healthcare Inc. database, estimated number of patients who switched medications, and impact of the coronavirus pandemic.

Background: The continuation rates of pharmacotherapy in schizophrenia exhibit variability, a phenomenon influenced by the specific antipsychotic agent prescribed and patient-related factors such as age and duration of illness. In this context, our study aims to elucidate the predictors of medication continuation for asenapine sublingual tablets, characterized by unique formulation properties. Methods: Our investigation leveraged real-world data collected through post-marketing surveillance in Japan, comprising 3236 cases. Utilizing multivariate logistic regression analysis, we identified patient-related factors associated with medication continuation as the primary outcome measure, subsequently employing survival analysis for further evaluation. Additionally, adverse event occurrence was assessed as a secondary outcome measure. Results: Multivariate logistic regression analysis unveiled significant predictors of asenapine continuation, notably including patient-related factors such as a chlorpromazine equivalent dose exceeding 600 mg/day and an illness duration of 25 years or more. While the overall continuation rate stood at 40.6%, patients exhibiting factors such as a chlorpromazine equivalent dose surpassing 600 mg/day or an illness duration exceeding 25 years demonstrated continuation rates of 46.3% and 47.9%, respectively. Remarkably, patients presenting both factors showcased the highest continuation rate at 52.5%. Conclusions: Our findings shed light on distinct patient-related predictors of asenapine continuation, deviating from those observed with other antipsychotic medications. This underscores the necessity of recognizing that predictive factors for antipsychotic medication continuation vary across different agents. Moving forward, elucidating these predictive factors for various antipsychotic medications holds paramount importance in schizophrenia treatment, facilitating the delivery of tailored therapeutic interventions for individual patients. [ABSTRACT FROM AUTHOR]

Objectives. Cognitive functions in almost all domains are lower in patients with schizophrenia than those in healthy controls, with the severity of impairment differing between domains. Treatments are being developed to improve cognitive impairment in patients with schizophrenia. However, the pattern of cognitive impairment must be clarified to facilitate treatment. Therefore, this study aimed to classify the patterns of cognitive impairment in individuals and provide treatment suggestions. Methods. Patients with schizophrenia were recruited from two psychiatric hospitals in Japan. Demographic and psychopathological symptoms were assessed using the Positive and Negative Symptoms Scale for Schizophrenia and neurocognitive functions, using the CogHealth battery. The following domains were assessed: processing speed, visual attention, working memory, visual learning, and spatial attention. The scores were standardised and assigned as the same-aged average score. Hierarchical cluster analysis using Ward's method was performed based on CogHealth scores. Subsequently, one-way analysis of variance (ANOVA) and Tukey's multiple comparisons were performed to compare the variables in each cluster. Results. In total, 133 participants were classified into four clusters: Cluster 1 (n = 16), with severe cognitive impairment and psychiatric symptoms and the longest stay; Cluster 2 (n = 44), with moderate cognitive impairment and psychiatric symptoms; Cluster 3 (n = 42), with preserved cognitive function, except for spatial perception, and mild psychiatric symptoms; and Cluster 4 (n = 31), with only memory and spatial perception impairment and mild psychiatric symptoms. Implications. The clusters indicate that impairment may occur in all or selective domains. Selective domain impairments may be in spatial perception or in spatial perception and memory. Therefore, it is recommended that treatments for cognitive dysfunction are developed into four subsets considering an individual's cognitive features. [ABSTRACT FROM AUTHOR]

Aim: Behavioral and psychological symptoms and delirium frequently occur in hospitalized older patients with pneumonia and are associated with longer hospital stays. Yokukan‐San (YKS, traditional Japanese [Kampo] medicine) and antipsychotics are often used to treat delirium and behavioral and psychological symptoms in Japan. Hence, this study aimed to assess the effectiveness and safety of the co‐administration of YKS with atypical antipsychotics in older patients with pneumonia. Methods: We used the Japanese Diagnosis Procedure Combination inpatient database to retrospectively identify older patients (≥65 years) hospitalized for pneumonia who received antipsychotics within 3 days of hospitalization. The patients were divided into two groups: those who received atypical antipsychotics alone (control group) and those who received both atypical antipsychotics and YKS (YKS group). We compared length of hospital stay, in‐hospital mortality, bone fractures, and administration of potassium products between the two groups using propensity score overlap weighting. Result: We identified 4789 patients in the YKS group and 61 641 in the control group. After propensity score overlap weighting, length of hospital stay was statistically significantly shorter in the YKS group (percentage difference −3.0%; 95% confidence interval −5.8% to −0.3%). The proportion of patients who received potassium products was higher in the YKS group (odds ratio 1.34; 95% confidence interval 1.15–1.55). In‐hospital death and bone fractures were not significantly different. Conclusion: Co‐administration of YKS with atypical antipsychotics could be a reasonable treatment option for hospitalized older patients with pneumonia and aggressive psychiatric symptoms. Geriatr Gerontol Int 2023; 23: 849–854. [ABSTRACT FROM AUTHOR]

Little is known about antipsychotic prescription patterns among children and adolescents in Japan, particularly in outpatient settings. We investigated the prevalence and trends of antipsychotic prescription for outpatients aged ≤ 17 years receiving a first antipsychotic prescription from 2006 to 2012 based on a large-scale dispensation dataset. Measurements included age, sex, department of diagnosis and treatment, type of prescription (monotherapy or polytherapy), antipsychotic dosage, and concomitant psychotropic drugs. Of the 10,511 patients, 65.1% were aged 13–17 years, and 52.9% were males. Second-generation antipsychotic monotherapy prescriptions increased from 53.8% in 2006 to 78.3% in 2012. Risperidone was the most frequently prescribed antipsychotic, followed by aripiprazole and olanzapine. Approximately 25.0% of patients were prescribed an initial dose less than recommended. Second-generation antipsychotic monotherapy is currently the most frequent prescription pattern among outpatients aged ≤ 17 years receiving an initial antipsychotic prescription. [ABSTRACT FROM AUTHOR]

Aim: We conducted a 1‐year retrospective mirror‐image study to investigate the effect of aripiprazole once monthly (AOM) on rehospitalization for bipolar disorder. Methods: Participants were recruited from psychiatric emergency and acute care hospitals in western Japan. We included 39 participants with bipolar disorder who had been administered AOM for at least 1 year with no missing medical records during the observational period. The primary outcomes were rehospitalization rate, number of rehospitalizations, total hospitalization days, and time to rehospitalization in the context of overall psychiatric readmissions. The significance level was set at p < 0.05. Results: AOM significantly reduced the rehospitalization rate from 23/39 (59%) to 7/39 (18%) (p = 0.001). The number of rehospitalizations decreased significantly from a mean of 0.85 per person‐year to 0.41 per person‐year (p = 0.048). The total hospitalization days significantly decreased from a mean of 34.9 days to 14.4 days (p = 0.008). AOM significantly prolonged the time to rehospitalization (p < 0.001). Conclusion: This study found that AOM reduces overall psychiatric rehospitalization for bipolar disorder based on data from 1 year before and after AOM administration in the real‐world setting. Future studies should examine the robustness and persistence of the rehospitalization preventive effect of AOM with larger sample sizes and longer observation periods beyond 1 year. [ABSTRACT FROM AUTHOR]

How physicians use antipsychotics for agitated delirium in the last days of life varies markedly, which could hamper the quality of care. To examine adherence to an algorithm-based treatment for terminal agitated delirium, and explore its effectiveness and safety. A single-center, prospective, observational study was conducted in a 27-bed palliative care unit in Japan. All adult cancer patients who developed agitated delirium with a modified Richmond Agitation-Sedation Scale (RASS) of +1 or more were included; the palliative care specialists determined that the etiology was irreversible, the estimated survival was three weeks or less, and the Eastern Cooperative Oncology Group (ECOG) performance status was three or four. Patients were treated with an algorithm to visualize how to use antipsychotics, with the treatment goal defined as no agitation (RASS≤0) or acceptable agitation for patients and families. We provided all patients nonpharmacological management to alleviate the symptoms of delirium and administered antipsychotic medications when the nonpharmacological approach was insufficient. We measured the adherence rate, RASS, Nursing Delirium Screening Scale items 2, 3, 4 (Nu-DESC), and Agitation Distress Scale item 2 (ADS) on days 0, 1, 3, 7, 14, 21, and 24 hours before death. A total of 164 patients were enrolled. Adherence rates were 99, 94, and 89%, and treatment goals were achieved in 66, 83, and 93% on days one, three, and seven, respectively. The mean RASS decreased from +1.41 to –0.84 on day three; Nu-DESC decreased from 4.19 to 1.83, and ADS decreased from 1.54 to 0.38. There were seven severe adverse events (Common Terminology Criteria for Adverse Events (CTCAE) of 3), including aspiration (n = 3), apnea (n = 2), tremor (n = 1), and muscle rigidity (n = 1) on day three. The algorithm-based treatment could be feasible, effective, and safe. Visualizing how palliative care specialists provide pharmacological management could be beneficial for nonspecialist clinicians, and clinical, educational, and research implications warrant further empirical testing. [ABSTRACT FROM AUTHOR]

To compare the effectiveness of different long-acting injectable antipsychotics (LAIs) (aripiprazole, paliperidone, risperidone, and fluphenazine/haloperidol) in patients with schizophrenia in Japan. We conducted a retrospective cohort study using two administrative claims databases. The study population consisted of outpatients with schizophrenia who initiated LAIs between May 1, 2015, and November 30, 2019. We directly compared the risk of psychiatric hospitalization and LAI discontinuation among the LAIs based on hazard ratios (HRs) using Cox proportional hazards regression models. The numbers of eligible patients who initiated aripiprazole, paliperidone, risperidone, and fluphenazine/haloperidol were 303, 124, 73, and 123, respectively. Regarding psychiatric hospitalization, aripiprazole and paliperidone were associated with significantly lower risk compared to fluphenazine/haloperidol (HR of aripiprazole: 0.47, 95 % CI: 0.28–0.78, HR of paliperidone: 0.50, 95 % CI: 0.28–0.89); HR of risperidone showed the same trend as the aripiprazole and paliperidone. Regarding LAI discontinuation, aripiprazole and paliperidone were associated with significantly lower risk of LAI discontinuation compared to fluphenazine/haloperidol (HR of aripiprazole: 0.53, 95 % CI: 95 % CI: 0.35–0.80, HR of paliperidone: 0.57, 95 % CI: 0.35–0.92). Aripiprazole was also associated with a significantly lower risk compared to risperidone (HR: 0.56, 95 % CI: 0.32–0.98). Our study suggests that aripiprazole and paliperidone are superior to fluphenazine/haloperidol in the risk of psychiatric hospitalization and LAI discontinuation. Aripiprazole is superior to risperidone in the risk of LAI discontinuation. [ABSTRACT FROM AUTHOR]

Background: Neonatal abstinence syndrome (NAS) induced by opiate use is common worldwide. Psychiatric drugs are a more common cause of NAS in Japan but infants of mothers taking psychiatric medications do not always develop NAS. The purpose of this study was to develop a practical model for predicting the onset of nonopiate‐induced NAS, using variables available at birth. Methods: In this diagnostic study, prediction models were developed using multivariable logistic regression with retrospective data collected at our hospital between 2010 and 2019. The NAS diagnosis was based on the Isobe score, and maternal medications were converted to dose equivalents. Results: A total of 164 maternal and infant dyads met the inclusion criteria; 91 were included in the analysis, of whom 29 infants (32%) were diagnosed with NAS. Final models were created with and without the drug indices. The model without the drug indices consisted of neonatal head circumference in z‐scores and Apgar scores at 5 min < 9, and the model with the drug indices included these, as well as antipsychotics and hypnotics indices. The C‐statistics were 0.747 (95% CI: 0.638–0.856), and 0.795 (95% CI: 0.683–0.907), respectively, indicating that the models possessed good predictive accuracy for NAS onset. Conclusions: This study developed models that predicted nonopiate‐induced NAS accurately. They may be further improved through the use of drug indices. [ABSTRACT FROM AUTHOR]

Background Although clozapine is effective for treatment-resistant schizophrenia (TRS), the rate of clozapine prescription is still low. Whereas antipsychotic monotherapy is recommended in clinical practice guidelines, the rate of antipsychotic polypharmacy is still high. There is little evidence on whether a clozapine prescription influences changes in the rate of monotherapy and polypharmacy, including antipsychotics and other psychotropics. We therefore hypothesized that the rate of antipsychotic monotherapy in patients with TRS who were prescribed clozapine would be higher than that in patients with schizophrenia who were not prescribed clozapine. Methods We assessed 8306 patients with schizophrenia nationwide from 178 institutions in Japan from 2016 to 2019. We analyzed the psychotropic prescription data at discharge in patients diagnosed with TRS and with no description of TRS (ND-TRS) based on the diagnosis listed in the discharge summary. Results The rate of antipsychotic monotherapy in the TRS with clozapine group (91.3%) was significantly higher than that in the TRS without clozapine group (45.9%; P  < 2.0 × 10−16) and the ND-TRS without clozapine group (54.7%; P  < 2.0 × 10−16). The rate of antipsychotic monotherapy without any other concomitant psychotropics in the TRS with clozapine group (26.5%) was significantly higher than that in the TRS without clozapine group (12.6%; P  = 1.1 × 10−6) and the ND-TRS without clozapine group (17.0%; P  = 5.9 × 10−6). Conclusions Clozapine prescription could be associated with a high rate of antipsychotic monotherapy. Patients will benefit from the correct diagnosis of TRS and thus from proper clozapine prescription. [ABSTRACT FROM AUTHOR]

Delirium occurs very frequently in cancer patients. Insomnia is a symptom of delirium. Lemborexant is a drug that regulates sleep–wake rhythms without causing extrapyramidal symptoms. Based on its ability to improve sleep, lemborexant is expected to have efficacy for insomnia with delirium. The purpose of this study was to determine the efficacy of lemborexant for insomnia in cancer patients with delirium. A retrospective observational study was conducted between July 2020 and February 2021. Fourteen patients (six females; mean age,69 years) were included. Lemborexant was effective in 11 of 14 (78.6%) patients. Of 14 patients, 10 had hyperactive delirium. Lemborexant might have similar efficacy for insomnia with and without delirium when compared with previous studies. The efficacy rate of lemborexant was 70% for patients with insomnia and hyperactive delirium. This study might lead to dose reductions of antipsychotic medications and fewer extrapyramidal symptoms in cancer patients with delirium. [ABSTRACT FROM AUTHOR]

Objective: Lurasidone is a second-generation antipsychotic (SGA) that contributes an antipsychotic and antidepressant effect, with low incidences of metabolic-related diseases and hyperprolactinemia for the treatment of psychological disorders. However, evidence on lurasidone is limited in psychiatric clinical settings. This study aimed to investigate the effect of short-term lurasidone treatment on metabolic effects and prolactin (PRL) levels, in relation to the differences of psychiatric disorders, lurasidone dosages, and introducing methods, in 35 female and 12 male Japanese inpatients with psychiatric disorders. Methods: Subjects were placed into six subgroups divided by three categories (schizophrenia/ schizoaffective disorder or bipolar disorder, 20mg/day or 40mg/day, adding or switching). Sequential changes in 10 items of metabolic parameters, including estimated insulin resistance and PRL levels at one month, were evaluated. The variations of metabolic parameters that were significantly changed from baseline were analyzed against sample characteristics and other metabolic parameter variations. Results: In the 40mg/day and switching introduction method groups, lurasidone significantly reduced body weight, body mass index (BMI), levels of alanine amiotransaminase, and levels of fasting blood glucose. PRL levels seemed to increase when lurasidone was added and decrease when lurasidone was switched to from other antipsychotics. Switching introduction method and higher dosage correlated with weight loss and lowering fasting blood glucose levels, respectively. Conclusion: Lurasidone administration offered the potential for weight loss, lowered serum blood glucose levels, and converging serum PRL concentrations. Moreover, switching introduction method with higher dosages might alleviate basal metabolism and glucose homeostasis. Further prospective studies combining measurements of serum insulin and psychometric evaluation will help to confirm our conclusions. [ABSTRACT FROM AUTHOR]

Aim: Globally, evidence from short‐term studies is insufficient for the guidelines to uniformly recommend a particular antipsychotic(s) for the maintenance treatment of schizophrenia. Therefore, long‐term comprehensive evaluation of antipsychotics is required from a social rehabilitation perspective, especially for drugs that have not yet been studied. The Japan Useful Medication Program for Schizophrenia (JUMPs) is a large‐scale, long‐term naturalistic study to present pivotal 52‐week data on the continuity of second‐generation antipsychotics (SGA: aripiprazole, blonanserin, and paliperidone). Methods: JUMPs was an open‐label, three‐arm, randomized, parallel‐group, 52‐week study. Enrolled patients had schizophrenia, were ≥20 years old, and required antipsychotic treatment or switched from previous therapy. The primary endpoint was treatment discontinuation rate over 52 weeks. Secondary outcomes included remission rate, social functioning, and quality‐of‐life scores [Personal and Social Performance Scale (PSP) and EuroQol‐5 dimensions], and safety. Results: In total, 251 patients received aripiprazole (n = 82), blonanserin (n = 85), or paliperidone (n = 84). The discontinuation rate (P = 0.9771) and remission rates (P > 0.05) over 52 weeks did not differ significantly between the three treatment groups. The discontinuation rates were 68.3%, 68.2%, and 65.5% in the aripiprazole, blonanserin, and paliperidone groups, respectively. Significant improvements (all P < 0.05) from baseline in PSP scores were observed at start of monotherapy, week 26, and week 52 in the overall cohort and blonanserin group and at week 26 in the aripiprazole group. The adverse event profile favored blonanserin. Conclusion: All three SGAs evaluated in this study showed similar treatment discontinuation rates in patients with chronic schizophrenia in Japan. [ABSTRACT FROM AUTHOR]

What is known and objective: Drug‐induced long QT syndrome (diLQTS) is a rare but serious adverse drug reaction. Drug‐drug interaction (DDI) is one of the risk factors for the development of diLQTS. However, the combinations of drugs that increase the risk of diLQTS have not been extensively investigated. This study was performed to analyse the potential DDIs that elevate the incidence of diLQTS using a spontaneous reporting system. Methods: The Japanese Adverse Drug Event Report database from April 2004 to January 2020 was used to assess adverse event reports. We calculated the reporting odds ratio and 95% confidence interval for signal detection. Results and discussion: Signals for concomitant use risk were detected in 31 drug combinations. Combinations of antipsychotics and antidepressants were the most common (olanzapine & fluvoxamine, olanzapine & trazodone, quetiapine & paroxetine, sulpiride & fluvoxamine, sulpiride & trazodone). Sixteen, 17 and 21 combinations were designated as requiring precaution for concomitant use in at least one of the package inserts in Japan, the United States and the United Kingdom, respectively, although no such precautions were described for the remaining combinations. On the contrary, a combination of bepridil & clarithromycin was categorized as "X (avoid combination)" and two combinations (chlorpromazine & haloperidol, amiodarone & metildigoxin) were classified as "D (modify regimen)" in the Lexicomp® risk rating. What is new and conclusion: This study identified 31 combinations of drugs that may elevate the risk of diLQTS. The use of these drug combinations should be monitored more carefully in future. [ABSTRACT FROM AUTHOR]

Objective: To identify factors affecting adherence to medication, a subjective questionnaire survey was administered to schizophrenia patients regarding the prescribed antipsychotic formulations. Methods: We evaluated the patients' satisfaction and dissatisfaction with prescribed antipsychotic formulations, and patients answered the Drug Attitude Inventory-10 Questionnaire (DAI-10). Inclusion criteria for patients are as follows: age between 20 and 75 years and taking antipsychotic agents containing the same ingredients and formulations, for at least 1 month. Results: In total, 301 patients answered the questionnaire survey. Tablets were found to be the most commonly used antipsychotic formulations among schizophrenia patients (n = 174, 57.8%), followed by long-acting injections (LAIs, n = 93, 30.9%). No significant differences in the formulation satisfaction level and DAI-10 scores were observed between all formulations. Formulations, except for LAI, were selected by physicians in more than half of the patients. Patients who answered "Decided by consultation with physicians" had significantly higher satisfaction levels and DAI-10 scores compared to those who answered "Decided by physicians" (4.11 ± 0.77 vs. 3.80 ± 1.00, p = 0.0073 and 6.20 ± 3.51 vs. 4.39 ± 4.56, p ＜ 0.001, respectively). Satisfaction levels moderately correlated with DAI-10 scores (r = 0.48, p ＜ 0.001). Conclusion: No formulation had a high satisfaction level in all patients, and it is important to be reflect the patients' individual preferences in pharmacotherapy. Shared decision-making in the selection of the formulations is seen to be useful for improving medication adherence. [ABSTRACT FROM AUTHOR]

In general, the course of schizophrenia is chronic accompanied not only by positive and negative symptoms but also by cognitive dysfunction associated with psychosocial disability, and thus treatment combining antipsychotics and psychological therapy is considered promising. This review focused on two prospective, open-label, multicenter, phase 3 long-term studies for approval of oral blonanserin for the treatment of schizophrenia. These two studies included both inpatients and outpatients with variable disease duration or symptom prominence according to the Positive and Negative Syndrome Scale (PANSS). The selected two studies consisted of almost the same study schedule and eligibility criteria but different protocols regarding prior medications and concomitant antipsychotics. The proportion of patients who had a baseline PANSS negative score higher than the positive score was 82.2 and 67.2% in the two studies. In both studies, patients with an illness duration of ≥ 10 years were the most common. Based on the clinical symptoms at baseline, the physician determined the treatment: blonanserin monotherapy, blonanserin in combination with the existing antipsychotic medication, or therapy simplified to haloperidol together with blonanserin. The 28-week completion rate for long-term blonanserin treatment was high in both studies (82.2 and 78.7%). The types of adverse events in both studies were similar to those in the preceding 8-week randomized, active-controlled studies in Japan, which were included in the application package for the approval of oral blonanserin for patients with schizophrenia. Long-term blonanserin use did not increase the risk of extrapyramidal symptoms but reduced the dose of antiparkinsonian drugs, minimally affecting functioning. In both studies, the PANSS total score, positive score, and negative score were improved at the last observation carried forward compared with those at baseline. In conclusion, blonanserin is useful for long-term treatment of chronic schizophrenic patients when the appropriate management of clinical symptoms and adverse drug reactions are applied. Blonanserin might represent a promising treatment option that partially or completely relieves patients with chronic schizophrenia of polypharmacy. Blonanserin may possibly fit both the current real-world clinical setting and the currently recommended approach to antipsychotic medication. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate the efficacy of lurasidone in acute schizophrenia in Japan and other countries. Methods: Subjects (aged 18–74 years) diagnosed with schizophrenia were randomized to lurasidone 40 mg/day or placebo. The primary efficacy endpoint was change from baseline on the Positive and Negative Syndrome Scale (PANSS) total score at Week 6. Secondary efficacy assessments included the Clinical Global Impression‐Severity Scale (CGI‐S). Safety endpoints included adverse events, and laboratory and electrocardiogram parameters. Results: A total of 483 subjects were randomized to lurasidone or placebo; 107 subjects were from Japan. Mean changes from baseline at Week 6 endpoint in PANSS total scores were −19.3 in the lurasidone group and −12.7 in the placebo group (treatment difference: P < 0.001, effect size = 0.41). Changes from baseline for Week 6 CGI‐S scores were −1.0 for lurasidone and −0.7 for placebo (treatment difference: P < 0.001, effect size = 0.41). All‐cause discontinuation during the 6‐week, double‐blind period was 19.4% for lurasidone and 25.4% for placebo, and discontinuation rates due to adverse event were 5.7% for lurasidone and 6.4% for placebo. The following common treatment‐emergent adverse events occurred in more than 2% on lurasidone and at a rate at least twice that of the placebo group: akathisia (4.0%), dizziness (2.8%), somnolence (2.8%), abdominal discomfort (2.0%) and asthenia (2.0%). No significant changes in bodyweight or metabolic parameters were observed. Conclusion: Lurasidone 40 mg once daily dosing demonstrated efficacy in a patient population with acute schizophrenia, including subjects from Japan, and was generally safe and well‐tolerated. [ABSTRACT FROM AUTHOR]

We examined the efficacy and safety of using antipsychotic medication for schizophrenia using only randomized trials of antipsychotic for schizophrenia conducted in Japan to avoid the biological and environmental heterogeneities caused by pooling data from various races and ethnicities. We searched for eligible studies on Embase, PubMed, and CENTRAL. Primary outcomes were improvement in Positive and Negative Syndrome Scale total score (PANSS−T) and all-cause discontinuation. Other outcomes were improvement in PANSS subscale scores, discontinuation due to adverse events or inefficacy, and the incidence of 16 adverse events. We calculated mean difference or risk ratios and 95% credible intervals. We identified 34 RCTs (6798 patients; mean study duration, 9.0 ± 4.24 weeks; proportion of male patients, 53.7%; mean age, 43.3 years). Besides placebo, studies included aripiprazole, asenapine, blonanserin, blonanserin-patch, brexpiprazole, clocapramine (no PANSS data), clozapine (no PANSS data), haloperidol, lurasidone, mosapramine, olanzapine, paliperidone, perospirone, quetiapine, and risperidone. Efficacy and safety profiles differed for antipsychotics used with schizophrenia in Japanese patients. All active treatments other than haloperidol and quetiapine outperformed placebo to improve PANSS−T. Asenapine, olanzapine, paliperidone, and risperidone outperformed placebo for all-cause discontinuation. Asenapine, blonanserin, blonanserin-patch, haloperidol, lurasidone, mosapramine, olanzapine, paliperidone, and risperidone outperformed placebo to improve PANSS positive subscale scores. Aripiprazole, asenapine, blonanserin, blonanserin-patch, brexpiprazole, lurasidone, olanzapine, paliperidone, perospirone, and risperidone outperformed placebo to improve PANSS negative subscale scores. The confidence in evidence of most outcomes was low or very low. Our results are similar to those of previous network meta-analysis involving various races and ethnicities. • We examined the efficacy and safety of antipsychotics for Japanese schizophrenia. • This study is a systematic review and network meta-analysis. • Our results are similar to those of a previous study involving various human races. [ABSTRACT FROM AUTHOR]

Long-acting injectable antipsychotics (LAI-APs) remain underutilized. One reason is the concern that LAI-APs might cause serious adverse events such as neuroleptic malignant syndrome (NMS) and lead to prolonged symptoms compared with oral treatment. Because the risk of NMS associated with LAI second-generation antipsychotics (LAI-SGAs) remains unclear, we compared reporting frequency, time to onset, and mortality of NMS between LAI- and oral SGAs using data from a Japanese spontaneous adverse event reporting database between April 2004 and September 2019. Of 5791 patients reporting adverse events due to LAI-SGAs or the equivalent oral SGAs, 768 (13%) developed NMS. LAI aripiprazole and LAI paliperidone were associated with a significantly lower reporting frequency of NMS than the equivalent oral SGAs (adjusted reporting odds ratio [95% confidence interval]: 0.35 [0.19-0.63] and 0.40 [0.27-0.59], respectively). Between 42% and 62% of the NMS associated with LAI- and oral SGAs other than LAI risperidone occurred within 30 days after initiation. The proportion of mortality due to NMS associated with oral aripiprazole was 13.1% and no deaths occurred in patients with NMS associated with LAI aripiprazole. The proportions of mortality due to NMS associated with oral risperidone/paliperidone, LAI risperidone, and LAI paliperidone were 8.8%, 4.2%, and 3.4%, respectively. Our findings showed that LAI-SGAs were not associated with a higher reporting frequency and mortality of NMS compared with oral SGAs, although clinicians need to closely monitor the occurrence of NMS not only during oral SGA treatment, but also, and in particular, in the early stage of LAI-SGA treatment. [ABSTRACT FROM AUTHOR]

Background and Objectives: Multi-regional clinical trials (MRCTs) are an efficient drug development strategy for eliminating drug lag in East Asian countries. In planning MRCTs according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use E17 guideline, it is expected that East Asian populations with relatively similar ethnicity can be pooled as one population. However, evidence supporting this assumption is limited. This study aimed to investigate population/regional differences considering influencing factors among East Asian regions using MRCT data as a research model. Methods: A retrospective analysis was conducted to determine the efficacy of two drugs, asenapine, a schizophrenia drug, and tadalafil, a dysuria drug for benign prostatic hyperplasia, using MRCT data from Japan, Korea, and Taiwan. First, predictive factors and effect modifiers were evaluated. Then, population/regional differences were evaluated using multivariate regression models, with the interaction term Region-by-Treatment group and adjustment for influencing intrinsic/extrinsic factors. Results: Among the 4 outcomes for the two drugs, no significant population/regional differences were detected (P > 0.05) by the adjusted regression models. The effect modifiers, such as pretreatment drug status or concurrent diseases, were common among countries. Conclusions: No significant population/regional efficacy differences were found for the two drugs among the three regions. This finding supported the possible applicability of the region pooling strategy for MRCTs in East Asia, emphasizing the benefits of exploring ethnic difference/influencing factors at an early stage to design further confirmatory studies. However, further evidence for various drugs should be accumulated. [ABSTRACT FROM AUTHOR]

Background: Clozapine is considered the gold standard medication for treatment-resistant schizophrenia (TRS). However, given that clozapine treatment is associated with the burden of regular blood monitoring and the risk of life-threatening adverse effects, high-dose olanzapine can serve as an alternative treatment. We conducted a bidirectional mirror-image study to evaluate the effectiveness of high-dose olanzapine compared with clozapine., Methods: We included patients with TRS who switched from olanzapine to clozapine or switched from clozapine to olanzapine, and received high-dose (>20 mg/d) olanzapine treatment for ≥4 weeks at Yamanashi Prefectural Kita Hospital. We obtained data on hospitalization, seclusion, and modified electroconvulsive therapy (mECT) during the clozapine phase and the olanzapine phase., Results: A total of 44 patients were included. When patients switched from high-dose olanzapine to clozapine (n = 32), significant reductions were found in the total days of seclusion, the total number of mECT, and the number of patients who received mECT at least once. When patients switched from clozapine to high-dose olanzapine (n = 12), a significant reduction was found in the number of patients who received mECT at least once. When data from both directions of treatment were combined, significant reductions were found in the total days of seclusion, the total number of mECT, and the number of patients who received mECT at least once in favor of clozapine., Conclusions: Findings suggest that high-dose olanzapine may not be as effective as clozapine for patients with TRS in real-world practice. However, it should be noted that there are unique circumstances that restrict the use of clozapine in Japan., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Previous studies conducted primarily in the USA and Europe have demonstrated the efficacy and safety of lurasidone 20–120 mg/day for the treatment of bipolar I depression. The aim of the current study was to evaluate the efficacy and safety of lurasidone monotherapy for the treatment of bipolar I depression among patients from diverse ethnic backgrounds, including those from Japan. Methods: Patients were randomly assigned to double‐blind treatment for 6 weeks with lurasidone, 20–60 mg/day (n = 184) or 80–120 mg/day (n = 169), or placebo (n = 172). The primary end‐point was change from baseline to Week 6 on the Montgomery–Åsberg Depression Rating Scale (MADRS). Results: Lurasidone treatment significantly reduced mean MADRS total scores from baseline to Week 6 for the 20–60‐mg/day group (−13.6; adjusted P = 0.007; effect size = 0.33), but not for the 80–120‐mg/day group (−12.6; adjusted P = 0.057; effect size = 0.22) compared with placebo (−10.6). Treatment with lurasidone 20–60 mg/day also improved MADRS response rates, functional impairment, and anxiety symptoms. The most common adverse events associated with lurasidone were akathisia and nausea. Lurasidone treatments were associated with minimal changes in weight, lipids, and measures of glycemic control. Conclusion: Monotherapy with once daily doses of lurasidone 20–60 mg, but not 80–120 mg, significantly reduced depressive symptoms and improved functioning in patients with bipolar I depression. Results overall were consistent with previous studies, suggesting that lurasidone 20–60 mg/day is effective and safe in diverse ethnic populations, including Japanese. [ABSTRACT FROM AUTHOR]

Background: Antipsychotics are commonly prescribed in high doses in combination with multiple psychotropic drugs. This study focused on the high‐dose antipsychotic prescriptions in patients with schizophrenia, while aiming to identify their associations with patients' characteristics and concurrent psychotropic prescriptions. Methods: This cross‐sectional study used claims data from a prefecture in Japan, between October 2014 and March 2015, to investigate antipsychotic prescriptions in adult outpatients with schizophrenia. The objective variable was the presence/absence of a high‐dose prescription. The explanatory variables included sex, age (category), presence of comorbid conditions, and the use of psychiatrist's therapy. Results: After exclusion, a total of 13 471 patients with schizophrenia were analyzed. The frequency of high‐dose prescriptions was higher in men, with chlorpromazine‐equivalent values highest in the age ranges of 45‐54 and 35‐44 years for men and women, respectively. Patients aged below 65 years with cerebrovascular diseases showed a decrease in high‐dose prescriptions. There was a high frequency of polypharmacy psychotropic drug use in combination with a high‐dose antipsychotic prescription in patients aged below 65 years. Conclusion: High‐dose antipsychotics are often used in combination with several psychotropic agents in patients with schizophrenia. Our findings emphasize the need to evaluate the prescribing behavior of physicians to avoid high‐dose antipsychotic prescriptions for improved patient care. [ABSTRACT FROM AUTHOR]

The current study aimed to describe the use of antipsychotics to clarify the gap between clinical guidelines and health care practice in Japan. We used data from the JMDC Claims Database (JMDC Inc., Tokyo, Japan), a nationwide claims database, from 2005 to 2016. Antipsychotics were defined as drugs coded as N05A with the Anatomical Therapeutic and Chemical (ATC) codes. We described the annual changes in proportions based on the number of patients prescribed any antipsychotics. From the database of 4,081,102 people, the data of 12,382 patients was extracted by applying the following exclusion criteria: no use of antipsychotics, missing the prescription date or dose, inpatients, prescribed antipsychotics only for use as needed, prescribed only injectable antipsychotics except for long-acting injections (LAIs), without schizophrenia as the primary disease, not exceeding 75 mg/day chlorpromazine equivalent, and less than 18 years old. The use of second-generation antipsychotics (SGA) has been expanding, while the use of first-generation antipsychotics has been decreasing. Aripiprazole accounted for the highest proportion of prescribed antipsychotics (31.9%) in 2016. Even though clozapine is categorized as a SGA, it accounted for a paltry 0.2%. The proportion of prescribed antipsychotics accounted for by LAIs was less than 5%. Although the use of antipsychotics for schizophrenia in Japan mostly corresponds to various clinical guidelines, limited use of clozapine and LAIs was identified. Further research focusing on the factors affecting the prescription of these underused antipsychotics may help advance the pharmacological therapy of schizophrenia. [ABSTRACT FROM AUTHOR]

Introduction The use of the blonanserin patch (BLO-P) for schizophrenia treatment was approved in Japan in 2019. This systematic review of trials in Japan assessed the efficacy and safety profile of BLO-P compared with other antipsychotics. Methods The systematic review included 6-week, double-blind, randomized, placebo-controlled, phase 3 trials in Japan that included patients with acute schizophrenia. Pooled data for patients receiving BLO-P 40 and 80 mg/day (BLO-P40+80) were compared with pooled data for patients receiving asenapine 10 and 20 mg/day (ASE10+20) and data for those receiving brexpiprazole 2 mg/day (BRE2) and paliperidone extended-release 6 mg/day (PAL-ER6). Results All the investigated treatments were superior to placebo in reducing the Positive and Negative Syndrome Scale (PANSS) total score; the Hedges' g values (95% confidence interval) for BLO-P40+80, ASE10+20, BRE2, and PAL-ER6 were−0.40 (−0.58,−0.22),−0.61 (−0.79,−0.42),−0.33 (−0.60,−0.07), and−0.69 (−0.93,−0.45), respectively. There were differences among the antipsychotics in the incidence of various individual adverse events. Discussion BLO-P40+80 may have a good efficacy/safety/tolerability profile for the treatment of patients with acute schizophrenia. [ABSTRACT FROM AUTHOR]

Aims: As the number of older people with dementia increases, safe pharmacotherapy in this population has attracted attention in recent years. The aims of this study were to clarify the prescribing patterns in older patients who were prescribed anti-dementia drugs and to investigate the association of potentially inappropriate medications (PIMs) with the use of anti-dementia drugs. Methods: Adults aged ≥65 years, who were prescribed anti-dementia drugs at 585 pharmacies across Japan (N = 7,953), were surveyed. The percentage of prescriptions of anti-dementia drugs and the effect of those prescriptions on PIMs were investigated. Results: Prescriptions of anti-dementia drugs were found in 4.4% of the entire study population. A multiple logistic regression analysis revealed that the use of anti-dementia drugs reduced the risk of prescribing psychotropic drugs, which represented PIMs, and that a combination of anti-dementia drugs (e.g., cholineesterase inhibitor with memantine) may reduce the risk of prescribing PIMs compared with monotherapy. Conclusion: The use of anti-dementia drugs was associated with fewer prescriptions of drugs considered as PIMs. [ABSTRACT FROM AUTHOR]

Aim: It is important to investigate the current prescription status and clinical outcomes of patients with schizophrenia receiving long‐acting antipsychotic injections. We aimed to determine the prescription proportion of long‐acting antipsychotic injections and hospital readmission proportions of patients with schizophrenia in Japan. Methods: An open dataset was created using data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Patient records with the term 'schizophrenia' were included. In Analysis 1, antipsychotic prescription proportions were determined for outpatients who had visited psychiatric facilities between 1 February 2015 and 31 March 2017. In Analysis 2, patients who had been discharged from a psychiatric facility and had received a long‐acting antipsychotic injection prescription within 90 days after initial discharge were selected; then, their readmission proportion was examined for 365 days after the initial discharge. Results: The long‐acting antipsychotic injection prescription proportion was 3.5% for outpatients with schizophrenia receiving antipsychotics. The readmission proportion was 41.0% in the entire patient population, 36.2% in patients receiving typical long‐acting antipsychotic injections alone, and 23.5% in patients receiving atypical long‐acting antipsychotic injections alone. Conclusion: Long‐acting antipsychotic injections are not yet widely used in Japan. The readmission proportion was lower in the patients receiving atypical than typical long‐acting antipsychotics injections. The results may provide important basic information to develop new future research questions but should be interpreted with caution because generalizability may be limited by the use of aggregated data and the data structure of the database used. [ABSTRACT FROM AUTHOR]

Background: Psychotropic polypharmacy is common in clinical practice although supporting evidence is limited. Extrapyramidal syndromes (EPS) are adverse events associated with use of psychotropic drugs, especially antipsychotics. There are quite a few reports that suggest association between each psychotropic drug and EPS; however, the risk of EPS associated with their polypharmacy has not been fully evaluated. This study aimed at examining the influence of psychotropic polypharmacy on EPS occurrence by drug category (anxiolytics, hypnotics, antidepressants, and antipsychotics). Methods: Sequence symmetry analyses were conducted using a large-scale Japanese health insurance claims database. This method assessed asymmetry in the distribution of EPS occurrence defined as both a diagnosis of EPS and a prescription for antiparkinsonian drugs before and after initiation of psychotropic drugs. The adjusted sequence ratio (ASR) and its 95% confidence interval (CI) were calculated. Results: All categories of psychotropic drugs (anxiolytics, hypnotics, antidepressants, and antipsychotics) were significantly associated with EPS, and the tendency was stronger in polypharmacy associated with them. A clearer association between polypharmacy of BZs and EPS was indicated. In the analyses by subclasses of drugs, BZs, tetracyclic antidepressants, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, typical and atypical antipsychotics were significantly associated with EPS. The ASR of atypical antipsychotics (ASR 11.3, 95% CI 7.95-16.4) was higher than that of typical ones (ASR 2.96, 95% CI 2.06-4.33). Conclusions: The association between psychotropic polypharmacy and EPS was indicated. Further investigation is needed to confirm these findings because of the pharmacoepidemiologic nature of this study. [ABSTRACT FROM AUTHOR]

In Japan, drug therapy for schizophrenia is characterized by high-dose antipsychotic polypharmacy, which is an uncommon approach internationally. In this study, we reduced the number of antipsychotic agents in 5 patients using the Safety Correction of High-dose Antipsychotic Polypharmacy (SCAP) method and conducted a survey regarding treatment satisfaction. The switch from polypharmacy to monotherapy was achieved in all patients. There was no deterioration in psychiatric symptoms, and adverse reactions were reduced. Three of the subjects were satisfied with the decrease in the number of antipsychotic agents and dose-reduction. These results suggest that the SCAP method is a safe and useful method that can be applied in a clinical setting. [ABSTRACT FROM AUTHOR]

Background and Objectives: In Japan, polypharmacy reduction policy, which reduces the reimbursement of medical cost, was introduced to address unnecessary psychotropic polypharmacy. The rule was applied to the prescriptions of three or more anxiolytics or three or more hypnotics in the policy introduced in 2012. The prescriptions of four or more antidepressants or four or more antipsychotics were added to the rule in the policy revised in 2014. Furthermore, the prescriptions of three or more drugs of anxiolytics, hypnotics, antidepressants, or antipsychotics were subject to the reduction criteria of the policy revision in 2016. Benzodiazepine receptor agonists (BZs) are classified both into anxiolytics and hypnotics, and the reduction rule was not applied to the category of BZs before April 2018. This study aimed to examine the effect of the policy on the prescriptions of four drug categories as well as BZs from the point of view of the number of drugs and doses. Methods: This was a retrospective observational study using a large-scale Japanese health insurance claims database. Patients who were prescribed at least one psychotropic drug (anxiolytic, hypnotic, antidepressant, or antipsychotic) during the study period (from April 2011 to March 2017) were selected. Segmented regression analysis was used to analyze the proportions of patients with three or more or four or more drugs as well as patients above clinically recommended doses, and the means of the average daily doses by drug category. Results: A total of 312,167 patients were identified as a study population. The proportions of patients with three or more drugs in anxiolytics, hypnotics, antidepressants, and antipsychotics significantly decreased after the introduction or revisions of the policy, but not BZs. The proportions of patients with three or more drugs in March 2017 were 0.9%, 2.0%, 1.2%, 2.4%, and 8.9% in anxiolytics, hypnotics, antidepressants, antipsychotics, and BZs, respectively. The effect of the policy in reducing the proportions of patients above clinically recommended doses was identified in antipsychotics after the revision in 2016, but not identified in the sum of anxiolytics and hypnotics as well as BZs after the revision in 2014, and antidepressants after the revision in 2016. The proportions of monotherapy were increased from April 2011 to March 2017 only for antidepressants (76.9% → 80.8%) and antipsychotics (79.8% → 82.1%), and not changed or decreased for anxiolytics (85.2% → 85.7%), hypnotics (78.6% → 77.6%), sum of anxiolytics and hypnotics (68.1% → 65.7%), BZs (68.0% → 67.3%), and sum of psychotropic drugs (52.1% → 49.9%). Conclusions: The polypharmacy reduction policy reduced the proportions of patients with three or more drugs in four drug categories, but not BZs. Only limited effects were seen for reducing the proportions of patients above clinically recommended doses. The policy was revised in April 2018 again. Further investigation is needed to examine the effect of the revision in 2018. [ABSTRACT FROM AUTHOR]

The aim of this article is to provide the rationale for the development of transdermal formulations of antipsychotics by highlighting their main advantages, starting with an overview of the antipsychotic formulations that are currently available on the market. Progress regarding transdermal antipsychotic formulations was investigated by performing a search of papers, patents and clinical trials published in the last 10 years. Available data on antipsychotic transdermal formulations are reported and discussed, focusing on the characteristics of the dosage forms and their ability to promote drug absorption. Despite the current availability of a large number of antipsychotics, only a few of these drugs (e.g. aripiprazole, asenapine, blonanserin, chlorpromazine, haloperidol, olanzapine, prochlorperazine, quetiapine, and risperidone) have been developed as transdermal delivery systems. Several papers and patents show that transdermal formulations, such as creams, films, gels, nanosystems, patches, solutions, and sprays, have been evaluated with the aim of expanding the clinical utility of antipsychotic drugs. In particular, the employment of different strategies, such as the use of nanoparticles/vesicles, or permeation enhancers as well as microneedles with iontophoresis, may improve the absorption of antipsychotic drugs through the skin. However, few clinical trials on transdermal delivery of antipsychotic drugs are available and only delivery systems containing asenapine and blonanserin have shown interesting clinical results in terms of pharmacokinetic data, efficacy, and tolerability. Recently, the transdermal patch formulation of blonanserin was approved in Japan for the treatment of schizophrenia. [ABSTRACT FROM AUTHOR]

Objectives: To examine factors that may affect the use and duration of seclusion and restraint (SR) in psychiatric inpatient settings. Methods: First, multivariable logistic regression analysis was used to examine factors associated with the use of SR in an unmatched case-control study, comparing SR cases and controls. Second, for patients that underwent SR, multivariable linear regression analysis was used to determine factors contributing to the duration of SR. Results: Out of 213 patients, 58 underwent SR. An F00 diagnosis, a history of epilepsy, antipsychotics usage and antidepressants usage were significantly associated with the use of SR (odds ratio = 7.98; 95% CI = 1.11–57.50, odds ratio = 4.89; 95% CI = 1.12–21.36, odds ratio = 4.59; 95% CI = 1.54–13.68 and odds ratio = 0.29; 95% CI = 0.10–0.86, respectively). An F00 and F32 diagnosis significantly extended the duration of SR (coefficient = 13.10; 95% CI = 2.11–24.11 and coefficient = 20.52; 95% CI = 9.68–31.37, respectively). Conclusions: A variety of factors are associated with the use and longer duration of SR. Given the potentially harmful effects of these practices, further studies with larger samples and a wider range of quantitative outcome measures are warranted. An F00 diagnosis, a history of epilepsy and antipsychotics usage may increase the use of SR. Antidepressants may decrease the use of SR. An F00 and F32 diagnosis may extend the duration of SR. [ABSTRACT FROM AUTHOR]

Background: Dementia with Lewy bodies (DLB) is a progressive form of dementia, accompanied by a range of behavioural and psychological symptoms. The aim of this study was to identify current clinical practice for the treatment of DLB in Japan. Methods: We conducted a survey of medical doctors engaged in the management of dementia in Japan. Participants were divided into two groups: psychiatrists (Group P) and neurologists or neurosurgeons (Group NS). Doctors completed a questionnaire and we analysed their responses to compare the two groups with regard to diagnosis and treatment of DLB, and in particular the treatment of behavioural and psychological symptoms of dementia (BPSD). Results: Responses suggested that Group P conducted biomarker examinations less frequently and decided on their own therapeutic strategies more frequently than did Group NS. Both groups most frequently selected hallucinations/delusions as the symptoms given highest treatment priority. More than 70% of respondents in both groups reported having difficulties in treating BPSD. Atypical antipsychotics were more frequently prescribed by Group P, but were also prescribed in 70% of patients in Group NS. A third of patients received atypical antipsychotics for more than 1 year. Conclusions: The responses to this survey highlighted the difficulties faced by clinicians managing patients with DLB and identified the need to effectively treat BPSD in such patients. [ABSTRACT FROM AUTHOR]

Objective: To investigated the effects of antipsychotics on rehabilitation outcomes for geriatric hip fracture inpatients. Design: Retrospective cohort study. Setting: The registry data from the Japan Rehabilitation Nutrition Database for analysis. Participants: Of the 234 patients in the Japan Rehabilitation Nutrition Database admitted between November 2015 and March 2018, 214 met the eligibility criteria. Measurements: The antipsychotics were phenothiazine, butyrophenone, benzamide, and atypical antipsychotics. For hip fracture patients, the following information was registered: (a) admission data: age, sex, Charlson Comorbidity Index, Functional Independence Measure (FIM) at admission, medications, height, body weight, and Mini Nutritional Assessment-Short Form score (MNA-SF) and (b) discharge data: discharge destination, FIM at discharge, MNASF, and total units of provided rehabilitation therapy (one unit = 20 minutes based on the national healthcare insurance policy). Results: Thirteen patients (6.1%) were prescribed antipsychotics. According to the multiple linear regression analysis, antipsychotics negatively affected FIM efficiency (β=-0.190, 95% confidence interval, -0.652 to -0.104, p=0.007). Furthermore, on logistic regression analysis, fall during hospitalization was correlated with the use of antipsychotics (odds ratio=4.376, 95% confidence interval: 1.153 to 16.612, p=0.030). Conclusion: The use of antipsychotics impaired the improvement of the activities of daily living (ADL) and increased the incidence of fall during hospitalization. Reviewing medication therapies at admission may further improve ADL. [ABSTRACT FROM AUTHOR]

Background: Long-acting injectable antipsychotics (LAIs) are regarded as an important alternative to oral medication for patients with schizophrenia. However, LAIs remain underutilized in clinical practice. Aims: The aims of this investigation were to 1) obtain information on patients' attitudes toward LAIs and 2) assess factors associated with patients' acceptance of LAIs, and 3) identify predictors of the discrepancy between patients and referring psychiatrists' opinions regarding the appropriateness for LAIs. Methods: Anonymized data were collected from a questionnaire distributed to 159 patients with schizophrenia and their referring psychiatrists at three psychiatric hospitals between February 2014 and July 2014. The patients completed an original questionnaire developed to evaluate their attitudes regarding LAIs. Regarding the appropriateness of LAI prescription, patients and their referring psychiatrists were asked to rate, on a 5-point scale, how appropriate they felt the depot prescription was for the patients. The participants also answered instruments to assess symptom severity, antipsychotic-induced extrapyramidal symptoms, functions, quality of life, and self-esteem levels. Results: Patients currently on LAIs have favorable attitudes toward LAIs with respect to side effects, relapse prevention, efficacy, pain, and cost. Expectation of relapse prevention was significantly associated with patients' acceptance of LAIs (answering that those drugs are appropriate for their own treatment). In addition, the discrepancy between the patients' and referring psychiatrists' opinions regarding the appropriateness of LAI treatment was significantly associated with symptom severity, expectation of relapse prevention, belief that LAIs are painful, and belief that LAIs offer a reduced range of antipsychotic choices. Conclusion: Attitudes toward LAIs need to be considered when deciding whether to prescribe this formulation. Access to information on LAIs, including their benefit in relapse prevention, might enhance the acceptance and use of this formulation among patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Although antipsychotic monotherapy is recommended as the main treatment for schizophrenia, antipsychotic polypharmacy is not rare in practice. However, longitudinal data on antipsychotic polypharmacy in schizophrenia treatment are limited. Methods: This longitudinal database study described antipsychotic polypharmacy in the treatment of schizophrenia in real-world settings in China and Japan. We retrieved information about antipsychotic treatment for schizophrenia from January 2010 to December 2014 from two hospital Electronic Medical Records databases in China and one claims database, Japan Medical Data Centre in Japan. Eligible patients had a diagnosis of schizophrenia (International Classification of Diseases, Tenth Revision F20.x) and at least one prescription for first or second generation antipsychotics. Antipsychotic polypharmacy was defined as having more than one antipsychotic medication overlapping for ⩾60 days. The Japan Medical Data Centre study cohort was further stratified by employees (insurance beneficiaries) and their dependents. Results: The study cohorts comprised 11,961 patients from China and 25,034 (10,661 employee sub-cohort and 14,373 dependent sub-cohort) from 14 days Japan Medical Data Centre in Japan. Most patients were prescribed monotherapy (87.3% in China and 80.1% in Japan), of which oral second-generation antipsychotics were the majority (78.9% in China and 65.8% in Japan). The prevalence rate of antipsychotic polypharmacy was 12.7% in China and 19.9% in Japan (13.7% in employees vs 24.5% in dependents). The most common combinations were two oral antipsychotics. Combinations of more than two drugs were uncommon in China (0.3%) but were prescribed for 5.3% of patients in Japan. Among patients treated with monotherapy, 12.6/100 person-years (11.8%) in China and 9.6/100 person-years (11.0%) in Japan switched to antipsychotic polypharmacy during follow-up. Younger patients were more likely to switch to antipsychotic polypharmacy than older patents in all study cohorts. Conclusion: The observed rates of antipsychotic polypharmacy ranged from 12.7% in China to 19.9% in Japan. Switching from monotherapy to antipsychotic polypharmacy was most likely to occur in younger patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Objective: The Japanese Psycho-Oncology Society and the Japanese Association of Supportive Care in Cancer have recently revised the clinical practice guidelines for delirium in adult cancer patients. This article reports the process of developing the revised guidelines and summarizes the recommendations made., Methods: The guidelines were developed in accordance with the Medical Information Network Distribution Service creation procedures. The guideline development group, consisting of multi-disciplinary members, created three new clinical questions: non-pharmacological intervention and antipsychotics for the prevention of delirium and trazodone for the management of delirium. In addition, systematic reviews of nine existing clinical questions have been updated. Two independent reviewers reviewed the proposed articles. The certainty of evidence and the strength of the recommendations were graded using the grading system developed by the Medical Information Network Distribution Service, following the concept of The Grading of Recommendations Assessment, Development, and Evaluation system. The modified Delphi method was used to validate the recommended statements., Results: This article provides a compendium of the recommendations along with their rationales, as well as a short summary., Conclusions: These revised guidelines will be useful for the prevention, assessment and management of delirium in adult cancer patients in Japan., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: Antipsychotics are commonly used for managing behavioral and psychological symptoms of dementia among elderly patients with dementia receiving antidementia drugs (ADDs). However, the use of antipsychotics among these patients has not been investigated since 3 ADDs were approved in 2011 in Japan.Method: We conducted a descriptive study using pharmacy prescription data and identified patients aged ≥65 years who were newly prescribed donepezil, memantine, rivastigmine, and galantamine between January 1, 2012, and September 30, 2014. We determined the proportion of antipsychotic prescription and the factors affecting antipsychotic prescription using multivariable Cox proportional hazard models.Result: Of 13 876 patients, 1705 were memantine users, and the proportion of antipsychotic prescription among them was the highest (11.1%). Adjusted hazard ratios for donepezil, rivastigmine, and galantamine were 0.66, 0.56, and 0.66, respectively, relative to that for memantine.Conclusion: Compared to other ADD users, new memantine users were most likely to be prescribed antipsychotics. [ABSTRACT FROM AUTHOR]

Antipsychotic drugs are associated with autonomic nervous system (ANS) dysfunction in patients with schizophrenia, but the effects of individual atypical antipsychotic drugs are not clear. This study investigated how four atypical antipsychotic drugs-risperidone, olanzapine, aripiprazole, and quetiapine-differ in their effects on ANS activity. A total of 241 Japanese patients with schizophrenia participated in this study. All of the participants received an atypical antipsychotic as monotherapy: 90 participants received risperidone, 68 olanzapine, 52 aripiprazole, and 31 quetiapine. ANS activity was assessed by means of a power spectral analysis of heart rate variability. The quetiapine group showed significantly diminished sympathetic and parasympathetic activity compared with the risperidone and aripiprazole groups and significantly lower sympathetic activity relative to olanzapine. In addition, multiple regression analysis showed that the type of antipsychotic drug significantly influenced ANS activity. We suggest that, among the antipsychotics examined-risperidone, olanzapine, aripiprazole and quetiapine-quetiapine has the strongest effect on ANS activity. [ABSTRACT FROM AUTHOR]

Brexpiprazole is currently approved in the United States for the treatment of schizophrenia and as adjunctive treatment of major depressive disorder. In Canada, it is approved for the treatment of schizophrenia. This study evaluated the pharmacokinetics (PK) and safety of brexpiprazole in Japanese patients with schizophrenia. This phase 1 study comprised a 14-day multiple-dose administration of brexpiprazole 1, 4, and 6 mg/day (n = 7, 8, and 6, respectively). Plasma concentrations and PK parameters and the influence of CYP2D6 polymorphisms (intermediate metabolizers [IMs] and extensive metabolizers [EMs]) on PK were evaluated. Adverse events (AEs) were recorded. The Cmax and AUC24h of brexpiprazole and its metabolite, DM-3411, showed dose-proportionality. The Cmax and AUC24h of brexpiprazole showed accumulation of about 2.5- to 5.5-fold on day 14, compared with those on day 1. The median tmax and the mean elimination half-life of brexpiprazole were 4-5 and 52-92 hours, respectively, across all doses on day 14. The C24h of brexpiprazole reached steady state after day 10 in all dose groups. The dose-normalized Cmax and AUC24h of brexpiprazole on day 14 were higher in IM patients than in EM patients. AEs were generally mild to moderate, with transient serum prolactin increase being the most common event. No clinically significant changes were observed for other clinical laboratory values. Brexpiprazole was safe and well tolerated in the studied Japanese patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Objective: Palliative care for dementia includes psychosocial interventions as first-line treatment for challenging behaviour. However, the national dementia plan in Japan contradicts recommendations for palliative care for dementia. This study aimed to examine the association between care quality for patients with dementia and professional caregivers' perspectives regarding palliative care for dementia in Japanese community care settings.Methods: In total, 2116 professional caregivers from 329 agencies (217 in-home long-term care support providers; 29 small-scale, multiple home-care providers; and 83 group homes) in Tokyo prefecture, Japan, completed cross-sectional, paper-based questionnaires about 3603 people diagnosed with dementia, in May 2016. Quality of care measures included physical restraint and antipsychotic medication use and quality of life. Patients' quality of life was assessed via the Japanese version of the Alzheimer's Disease Health-related Quality of Life scale. The Japanese version of the Questionnaire on Palliative Care for Advanced Dementia was used to assess professional caregivers' knowledge and attitudes regarding palliative care for dementia.Results: Professional caregivers' knowledge and attitudes regarding palliative care for dementia were positively associated with quality of life in patients with dementia. Physical restraint and antipsychotic medication were used regardless of professional caregivers' knowledge and attitudes.Conclusions: Professional caregivers' perspectives regarding palliative care for dementia could have exerted a positive effect on quality of life in patients with dementia. A national strategy for advocacy and the protection of adults is required to integrate several laws and guidelines and prevent the use of antipsychotics as a form of chemical restraint. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 70-year-old Japanese man with retinal detachment and having surgery. Topics include describing the experience of the effects of combination pharmacotherapy with asenapine and escitalopram drug therapy on MDDPF; and considering the improvement in several symptoms related to the broad anti-depressive effect, anti-aggressive effect, and immediate efficacy of asenapine.

We evaluated the efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents (6-17 years) with autism spectrum disorder (ASD) in a randomized, double-blind, placebo-controlled 8-week study in Japan. Patients received flexibly dosed aripiprazole (1-15 mg/day) or placebo. Ninety-two patients were randomized to placebo (n = 45) or aripiprazole (n = 47). Aripiprazole produced a significant improvement in the mean parent/caregiver-rated Aberrant Behavior Checklist Japanese Version irritability subscale score relative to placebo from week 3 through week 8. Administration of aripiprazole provided significantly greater improvement in the mean clinician-rated Clinical Global Impression-Improvement scores than placebo from week 2 through week 8. All patients randomized to aripiprazole completed the study, and no serious adverse events were reported. Three patients in placebo group discontinued. Aripiprazole was effective and generally safe and well-tolerated in the treatment of irritability associated with ASD in Japanese children and adolescents. [ABSTRACT FROM AUTHOR]

Objective: Paliperidone palmitate once-monthly injectable (PP1M) is approved in Japan and other countries for the treatment of schizophrenia. During the 6 month Japanese early postmarketing phase vigilance (EPPV) period, 32 deaths were reported. This report reviews potential contributing factors to the fatal outcomes in the PP1M-treated population.Research Design and Methods: All spontaneously reported adverse events following PP1M use received during EPPV from 19 November 2013 to 18 May 2014 were entered into the global safety database and these events were analyzed.Results: During the EPPV period, 10,962 patients were estimated to have been treated with PP1M in Japan. The mortality reporting rate during this EPPV period was higher than that observed in the US or globally after PP1M launch (5.84, 0.43, and 0.38 per 1000 patient-years, respectively), but was consistent with the mortality incidence rates (10.2 per 1000 person-years) observed during interventional clinical studies in Japan and in observational patient cohorts. Of the 32 deaths reported during the Japanese PP1M EPPV period, 19/32 (59.4%) were in patients over 50 years of age, 23/32 (71.9%) reported cardiovascular risk factors and 25/32 (78.1%) received antipsychotic polypharmacy.Conclusions: Based on this review of the 32 fatal cases in the PP1M EPPV period, the observed death rate does not necessarily result from a risk with PP1M treatment in Japanese patients. The higher mortality reporting rates in Japan may be attributed to a variety of factors: the effectiveness of mortality reporting in the unique Japanese EPPV program, the advanced age of the fatal cases, high cardiovascular risk factors, multiple underlying diseases and high antipsychotic polypharmacy among the cases with fatal outcomes. [ABSTRACT FROM AUTHOR]

Objective: In child and adolescent psychiatry, the off-label prescribing of psychotropic medications is common. The purpose of this study was to examine the experiences of Japanese child and adolescent psychiatrists with off-label prescribing to children and/or adolescents (hereafter referred to as "children") and to identify the factors associated with these experiences.Methods: A prospective questionnaire was sent to 1628 psychiatrists belonging to the Japanese Society for Child and Adolescent Psychiatry. Stepwise logistic regression analyses were used to determine whether demographic characteristics or categories of psychotropic medications were able to independently predict patient refusals of off-label prescribing.Results: The final sample included 447 psychiatrists, and 93% of the respondents (416/447) had experiences with off-label prescribing to children. In addition, 39.7% of the respondents (165/416) experienced patient refusal of off-label prescribing when they informed the children and/or parents of the prescribing. The most commonly prescribed off-label psychotropic medications were antipsychotics (82.0%). Patient refusal was significantly more frequent when the respondents informed parents (p=0.02) and children (p<0.01) about off-label prescribing than when they did not. A stepwise logistic regression analysis revealed that informing parents (odds ratio [OR], 2.73; 95% confidence interval [CI], 1.09-6.82) or children (OR, 1.70; 95% CI, 1.12-2.58) about off-label prescribing and antidepressant use (OR, 2.98; 95% CI, 1.25-7.10) increased the odds of patient refusal of off-label prescribing; however, prescribers' years in practice decreased the odds (OR, 0.98; 95% CI, 0.96-1).Conclusions: Off-label prescribing of psychotropic medications is common among child and adolescent psychiatrists in Japan. Furthermore, the psychiatrists' experiences with patient refusal of off-label prescribing were significantly associated with informing the parents/patients about off-label prescribing, particularly with regard to use of antidepressants. Further studies are required to support the development of decision making among clinicians. [ABSTRACT FROM AUTHOR]

Background: Knowledge of the epidemiology of adverse drug events (ADEs) and medication errors in psychiatric inpatients is limited outside Western countries. The nature of ADEs and medication errors are important for improving the quality of care worldwide; therefore, we conducted the Japan Adverse Drug Events Study, a series of cohort studies at several settings in Japan. Methods: This report included 448 inpatients with 22,733 patient-days in a psychiatric hospital and psychiatric units at a tertiary care teaching hospital over 1 year. Four psychiatrists and two other physicians reviewed all medical charts and related documents to identify suspected incidents. The physicians later classified those incidents into ADEs, potential ADEs, medication errors, or exclusions and evaluated the severity and preventability if the incidents were events. Results: During the study period, we identified 955 ADEs and 398 medication errors (incidence: 42.0 and 17.5 per 1000 patient-days, respectively). Among ADEs, 1.4%, 28%, and 71% were life-threatening, serious, and significant, respectively. Antipsychotics were associated with half of all ADEs. The incidence of medication errors was higher in medical care units than in acute and nursing care units (40.9, 15.6, and 17.4 per 1000 patient-days, respectively). The monitoring and ordering stages were the most common error stages (39% and 34% of all medication errors, respectively), and 76% of medication errors with ADEs were found at the monitoring stage. Non-psychiatric drugs were three times as likely to cause ADEs with errors compared to psychiatric drugs. Conclusions: Antipsychotic use, inadequate monitoring, and treatment of physical ailments by psychiatrists may contribute to the high incidence of medication errors and ADEs among psychiatric inpatients in Japan. Psychiatrists should be cautious in prescribing antipsychotics or unfamiliar medications for physical problems in their psychiatric patients, and should monitor patients after medication administration. [ABSTRACT FROM AUTHOR]