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Objectives: To evaluate the short-term efficacy and safety of blonanserin in adolescents with schizophrenia.Methods: This 6-week multicenter, double-blind, randomized, placebo-controlled study investigated fixed-dose blonanserin (8 or 16 mg/day) in patients 12-18 years of age diagnosed with schizophrenia, as indicated by a Positive and Negative Syndrome Scale (PANSS) total score of 60-120 and a Clinical Global Impressions-Severity score of >= 3. The primary endpoint was change from baseline to week 6 in the PANSS total score, using a mixed model for repeated measures analysis. Safety was assessed by the incidence and severity of adverse events (AEs).Results: Among 151 randomized patients, 150 were included in the primary analysis population. Demographic and clinical characteristics were similar across groups at baseline. The rate of study discontinuation was 14.9%, 23.5%, and 28.3% in patients administered with placebo, blonanserin 8 mg/day, and blonanserin 16 mg/day, respectively. The least-squares mean change (95% confidence interval [CI]) from baseline to week 6 in PANSS total score was -10.6 (-16.10 to -5.10), -15.3 (-20.80 to -9.86), and -20.5 (-25.89 to -15.16) in patients administered placebo, 8 mg/day blonanserin, and 16 mg/day blonanserin, respectively. The 16-mg/day blonanserin group showed significantly greater reduction in the PANSS total score than the placebo group (least-squares mean difference [95% CI]: -9.9 [-17.61 to -2.25], p = 0.012, effect size: 0.538), although the 8-mg/day group showed no significant difference. The incidence of AEs such as akathisia, somnolence, and hyperprolactinemia was higher in the blonanserin groups than in the placebo group. AEs associated with blonanserin were generally mild and were consistent with its known profile in adults with schizophrenia.Conclusions: Blonanserin achieved a sufficient efficacy in adolescent patients, and the safety profile was similar to that in adults, which suggests that blonanserin may be a safe treatment option for adolescents with schizophrenia.Study registration number: Japic CTI-111724.

Objectives: To evaluate the long-term efficacy and safety/tolerability of oral blonanserin in adolescents with schizophrenia (Study registration number: JapicCTI-111725). Methods: This 52-week, mul...

Blonanserin an antipsychotic novel drug used for the treatment of schizophrenia has antagonist properties for dopamine D2 and serotonin 5-HT2. On the other hand, it lacks adrenergic-α1, muscarinic M1, and histamine H1 antagonist activities. Clinical studies demonstrated in Japan had shown to be more effective for treating negative as well as positive schizophrenic symptoms. This drug was accepted and approved worldwide in the treatment of schizophrenia. A new HPLC method was developed and validated for the estimation of Impurities of Blonanserin (BNS) to ensure that the methodology meets the requirements of the target analysis application. Active and efficient chromatographic separation was achieved on a Zorbax Bonus RP EP C18 column having a particle size of 5μm, with dimensions of 250mm × 4.6 mm, mobile phase containing pH 2.4 buffer and Organic, with 1.0 ml /min flow rate, column oven temperature at 30oC and the eluent detection at 245 nm. The method shows well-separated impurities, is specific without interference from blank solution with resolution more than 1.2 between any of the impurity, correlation coefficient more than 0.99 showing good linearity; mean recovery ranging from 97% to 105% and is very sensitive at lower detection and quantification limits. This method was well developed and has been applied successfully to monitor and estimate impurities in Blonanserin.

Tardive dyskinesia (TD) is a common side effect of antipsychotics, and it remains a persistent and challenging problem. The blonanserin transdermal patch, developed in Japan and launched in September 2019, is the first antipsychotic transdermal treatment. Here, we describe a patient with schizophrenia who exhibited markedly improved orofacial dyskinesia after switching from blonanserin tablets to blonanserin transdermal patches. We speculate that the patch formulation might have led to more stable plasma blonanserin levels, thus reducing the side effects. Specifically, the patch formulation might have contributed to stable plasma levels via the continuous and direct absorption of blonanserin through the skin., The present case report shows that switching from blonanserin tablets to blonanserin patches may reduce EPSs while maintaining a good therapeutic effect.

The clinical applications of antipsychotics for symptoms unrelated to schizophrenia, such as behavioral and psychological symptoms, in patients with Alzheimer's disease, and the likelihood of doctors prescribing antipsychotics for elderly people are increasing. In elderly people, drug-induced and aging-associated urinary disorders are likely to occur. The most significant factor causing drug-induced urinary disorders is a decrease in urinary bladder smooth muscle (UBSM) contraction induced by the anticholinergic action of therapeutics. However, the anticholinergic action-associated inhibitory effects of antipsychotics on UBSM contraction have not been sufficiently assessed. In this study, we examined 26 clinically available antipsychotics to determine the extent to which they inhibit acetylcholine (ACh)-induced contraction in rat UBSM to predict the drugs that should not be used by elderly people to avoid urinary disorders. Of the 26 antipsychotics, six (chlorpromazine, levomepromazine (phenothiazines), zotepine (a thiepine), olanzapine, quetiapine, clozapine (multi-acting receptor targeted antipsychotics (MARTAs))) competitively inhibited ACh-induced contractions at concentrations corresponding to clinically significant doses. Further, 11 antipsychotics (perphenazine, fluphenazine, prochlorperazine (phenothiazines), haloperidol, bromperidol, timiperone, spiperone (butyrophenones), pimozide (a diphenylbutylpiperidine), perospirone, blonanserin (serotonin-dopamine antagonists; SDAs), and asenapine (a MARTA)) significantly suppressed ACh-induced contraction; however, suppression occurred at concentrations substantially exceeding clinically achievable blood levels. The remaining nine antipsychotics (pipamperone (a butyrophenone), sulpiride, sultopride, tiapride, nemonapride (benzamides), risperidone, paliperidone (SDAs), aripiprazole, and brexpiprazole (dopamine partial agonists)) did not inhibit ACh-induced contractions at concentrations up to 10-5 M. These findings suggest that chlorpromazine, levomepromazine, zotepine, olanzapine, quetiapine, and clozapine should be avoided by elderly people with urinary disorders.

Background The antipsychotic olanzapine is a first-line drug in the treatment of schizophrenia while blonanserin is indicated in resistant cases of schizophrenia when the first line antipsychotics have failed. There are very limited studies available world-wide as well as in India that compare blonanserin with other antipsychotics in the setting of schizophrenia. Aims To study the efficacy, safety and tolerability of olanzapine and blonanserin in Schizophrenia. Settings and Design: The study was a prospective, observational, parallel group study done on schizophrenia patients aged between 18-50 years of both sexes at an outpatient Department of Psychiatry, in a tertiary medical college. The study was conducted from February 2015 to October 2016, with follow ups at weeks 4, 8 and 12. Materials and Methods The efficacy parameters were measured by the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression (CGI) rating. The safety parameters included the vital signs, haematological profile, lipid profile, blood sugar monitoring. Adverse drug reactions and compliance to therapy was observed through-out the study period. Appropriate statistical tests were applied to detect any significant within and between group differences using Microsoft Excel 2007 and SPSS version 17. Results There was significant decrease in the mean total score on the BPRS and CGI-S in the blonanserin arm at the 2nd and last follow up visit (p value < 0.001). Compliance was good in both groups (≤ 20% missed pills). Overall, 77 treatment-emergent adverse events were present from 56 patients. Twenty three subjects of the blonanserin arm and 33 subjects in the olanzapine arm at least experienced one adverse event (p = 0.006), metabolic adverse effects were more common with olanzapine, whereas insomnia, headache and somnolence were more often seen with blonanserin. Conclusions In the present study, blonanserin provided significantly better outcomes than olanzapine with respect to BPRS, CGI-S scores.

As a novel antipsychotic drug, the mechanism of action of blonanserin receptor makes it play an important role in improving cognitive dysfunction in patients with schizophrenia. However, there are few effective studies on the use of blonanserin in the treatment of cognitive impairment in patients with schizophrenia, and we hope to explore the efficacy of blonanserin in the treatment of cognitive impairment in schizophrenics through this study.

As a new type of antipsychotic drug, different from most atypical antipsychotic drugs, blonanserin has a slightly higher affinity for dopamine D2 receptor than 5-HT2A receptor, and is an antagonist of both and dopamine D3 receptor. However, it had almost no blocking effect on adrenaline 1, histamine HI receptor and acetylcholine M1 receptor. The action mechanism of multiple receptors of Blonanserin makes it play an important role in improving the cognitive impairment of schizophrenia. As an antipsychotic drug with unique antagonistic effect of D3 receptor, Bunanserin is expected to play a greater role in the improvement of patients' cognitive function.

Objective In a number of controlled clinical trials and naturalistic studies, aripiprazole once monthly (AOM) has been found to be effective and safe as acute and maintenance treatment options for schizophrenia. However, such clinical data have been presented in selected patient population (i.e., antipsychotic monotherapy, etc.), in particular, clinical information on switching to AOM from antipsychotic polypharmacy and/or other long acting injectable antipsychotics (LAIs) has been scarce till today. Methods The study period was from the first switching day to AOM up to 12 months in patients with antipsychotic polypharmacy (APpoly)/LAIs (baseline, month 3, month 6, and month 12). Available demographics and clinical information were retrieved from electronic medical records (EMRs). Available scores of Global Assessment of Functioning (GAF), Clinical Global Impression-Clinical Benefit (CGI-CB), CGI-severity, Visual Analog Scale on Satisfaction-Patient/Health Professional (VAS-P/HP), and the Positive and Negative Syndrome Scale-Insigh (PANSS-I) scores were also taken from EMR. Proportional change of functional impairment before and after AOM was also captured. Results Data of 18 patients were available. Most commonly used combined APs before AOM were aripiprazole, blonanserin, quetiapine, and risperidone. At least 2 APs (n = 2.4) were combined before AOM. Scores of GAF (10.7% increase), CGI-CB (46.2% decrease), VAS-P (47.8% increase), VAS-HP (40.8% increase), and PANSS-I (27.9% increase) (all p = 0.001) were significantly improved from baseline to month 12, respectively. Approximately 59% of patients improved individual functioning with different level (i.e., employment, back to school, etc.) after AOM treatment at month 12. Conclusion The present study have clearly shown the clinical benefit and utility of switching to AOM for treatment of patients with APpoly/LAIs in routine practice. Subsequent, adequately-powered, well-controlled clinical trials may be necessary to confirm our findings in near future.

BACKGROUND Gambling disorder is characterized by excessive and recurrent gambling and can have serious negative social consequences. Although several psychotherapeutic and pharmacological approaches have been used to treat gambling disorder, new treatment strategies are needed. Growing evidence suggests that dopamine D3 receptor plays a specific role in the brain reward system. AIM To investigate if blonanserin, a dopamine D3 receptor antagonist, would be effective in reducing gambling impulses in patients with gambling disorder. METHODS We developed a study protocol to measure the efficacy and safety of blonanserin as a potential drug for gambling disorder, in which up to 12 mg/d of blonanserin was prescribed for 8 wk. RESULTS A 37-year-old female patient with gambling disorder, intellectual disability, and other physical diseases participated in the pilot study. The case showed improvement of gambling symptoms without any psychotherapy. However, blonanserin was discontinued owing to excessive saliva production. CONCLUSION This case suggests that blonanserin is potentially an effective treatment for patients with gambling disorder who resist standard therapies, but it also carries a risk of adverse effects. Further studies are needed to confirm the findings.

Blonanserin is an atypical antipsychotic drug with high affinity and selective antagonism for dopamine D2 and D3 and serotonin 5-HT2A receptors. Blonanserin transdermal patch is the first transdermal formulation developed for the treatment of schizophrenia. The purpose of this population pharmacokinetic (PPK) analysis was to evaluate the characteristics of blonanserin pharmacokinetics after transdermal patch application, to estimate the daily fluctuation in blonanserin plasma concentration, and to evaluate the impact of patch application noncompliance to support usage in clinical settings. A total of 3747 plasma blonanserin concentrations from 9 clinical studies (93 healthy volunteers and 348 patients with schizophrenia) were used in the PPK analysis. The plasma concentration was predicted using the final PPK model, and dopamine D2 receptor occupancy was estimated on the basis of the results of a separately reported positron emission tomography study. A 2-compartment, parallel zero-order absorption with a lag time and first-order elimination model was developed to describe the pharmacokinetics of blonanserin, including the change in absorption rate during patch application. The maximum/minimum ratio of plasma concentration was estimated as 1.10 at steady state, indicating minimal fluctuation. In the case of failure to remove the previous patch or a missing application, the increase or decrease in plasma concentration and dopamine D2 receptor occupancy was

Background Catatonia is a psychomotor syndrome that presents various symptoms ranging from stupor to agitation, with prominent disturbances of volition. Its pathogenesis is poorly understood. Benzodiazepines and electroconvulsive therapy (ECT) are safe and effective standard treatments for catatonia; however, alternative treatment strategies have not been established in cases where these treatments are either ineffective or unavailable. Here, we report a case of catatonia associated with late-life psychosis, which was successfully treated with lithium. Case presentation A 66-year-old single man with hearing impairment developed hallucination and delusions and presented with catatonic stupor after a fall. He initially responded to benzodiazepine therapy; however, his psychotic symptoms became clinically evident and benzodiazepine provided limited efficacy. Blonanserin was ineffective, and ECT was unavailable. His catatonic and psychotic symptoms were finally relieved by lithium monotherapy. Conclusions Catatonic symptoms are common in patients with mood disorders, suggesting that lithium may be effective in these cases. Moreover, lithium may be effective for both catatonic and psychotic symptoms, as it normalizes imbalances of excitatory and inhibitory systems in the brain, which underlies major psychosis. Cumulative evidence from further cases is needed to validate our findings.

Rationale Unlike other antipsychotics, our previous positron emission tomography (PET) study demonstrated that a single dose of blonanserin occupied dopamine D3 as well as dopamine D2 receptors in healthy subjects. However, there has been no study concerning the continued use of blonanserin. Objectives We examined D2 and D3 receptor occupancies in patients with schizophrenia who had been treated with blonanserin. Methods Thirteen patients with schizophrenia participated. PET examinations were performed on patients treated with clinical dosage of blonanserin or olanzapine alone. A crossover design was used in which seven patients switched drugs after the first scan, and PET examinations were conducted again. D2 and D3 receptor occupancies were evaluated by [11C]-(+)-PHNO. We used nondisplaceable binding potential (BPND) of 6 healthy subjects which we previously reported as baseline. To consider the effect of upregulation of D3 receptor by continued use of antipsychotics, D3 receptor occupancy by blonanserin in seven subjects who completed 2 PET scans were re-analyzed by using BPND of olanzapine condition as baseline. Results Average occupancy by olanzapine (10.8 ± 6.0 mg/day) was as follows: caudate 32.8 ± 18.3%, putamen 26.3 ± 18.2%, globus pallidus − 33.7 ± 34.9%, substantia nigra − 112.8 ± 90.7%. Average occupancy by blonanserin (12.8 ± 5.6 mg/day) was as follows: caudate 61.0 ± 8.3%, putamen 55.5 ± 9.5%, globus pallidus 48.9 ± 12.4%, substantia nigra 34.0 ± 20.6%. EC50 was 0.30 ng/mL for D2 receptor for caudate and putamen (df = 19, p < 0.0001) and 0.70 ng/mL for D3 receptor for globus pallidus and substantia nigra (df = 19, p < 0.0001). EC50 for D3 receptor of blonanserin changed to 0.22 ng/mL (df = 13, p = 0.0041) when we used BPND of olanzapine condition as baseline. Conclusions Our study confirmed that blonanserin occupied both D2 and D3 receptors in patients with schizophrenia.

Background Transdermal antipsychotic patch formulations offer potential benefits, including improved adherence. This study investigated the striatal dopamine D2 receptor occupancy with daily blonanserin transdermal patch application. Methods This open-label, phase II study enrolled 18 Japanese outpatients (20 to Results Of 18 patients who started the blonanserin tablet treatment period, 14 patients completed treatment. Mean D2 receptor occupancy for blonanserin tablets 8 mg/d (59.2%, n = 5) and 16 mg/d (66.3%, n = 9) was within the values for blonanserin patches: 10 mg/d (33.3%, n = 3), 20 mg/d (29.9%, n = 2), 40 mg/d (61.2%, n = 3), 60 mg/d (59.0%, n = 3), and 80 mg/d (69.9%, n = 3). Occupancy generally increased with increasing blonanserin dose for both formulations with the half maximal receptor occupancy for tablets and patches associated with doses of 6.9 mg/d and 31.9 mg/d, respectively. Diurnal variability in occupancy was lower during transdermal patch treatment than during tablet treatment. Blonanserin transdermal patches were well tolerated with no major safety concerns. Conclusions Blonanserin patches (40/80 mg/d) have lower diurnal variability in occupancy than blonanserin tablets (8/16 mg/d), and patches at doses of 40 mg/d and 80 mg/d appear to be a suitable alternative for blonanserin tablets at doses of 8 mg/d and 16 mg/d, respectively. Blonanserin patches represent a potential new treatment option for patients with schizophrenia. Trial registry JAPIC Clinical Trials Information registry (www.clinicaltrials.jp; JapicCTI-No: JapicCTI-121914).

Objective This study was done for collection of real world data of Aripiprazole Once Monthly (AOM) in patients with schizophrenia. Methods The observation was up to 12 months from the first use of AOM in patients with antipsychotic polypharmacy (APpoly)/other long acting injectable antipsychotics (LAIs) for treatment of schizophrenia in daily practice. Demographics and available clinical information such as The Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-severity (CGI-S) scores were retrieved from the electronic medical record (EMR). Adverse events were also noted as described in EMR. Results Eighteen patients were found to be switched from APpoly/LAIs. Mean numbers of previous APs treatment failure and immediate prior APs were 2.2 and 2.4, respectively; most commonly used APs before AOM were aripiprazole, blonanserin, quetiapine, and risperidone. Mean number of combined APs before AOM significantly decreased from 2.4 use to 0.7 at month 12 (p < 0.0001). The PANSS total (71.7 to 62.1, p = 0.000) and CGI-S (3.4 to 3.1, p = 0.008) scores were also significantly decreased from baseline (first use of AOM) to month 12, respectively. Other various psychotropics including anxiolytics were also significantly and substantially decreased at some point from baseline throughout the observation period as well. Mild hand tremor and akathisia were developed in 3 patients. Conclusion The present observation study clearly confirmed the use of AOM should be also effective and tolerable treatment option for patients with APpoly/LAIs in the real world practice. Subsequent, adequately-powered, and well-controlled clinical trials are warranted in near future.

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.

Highlights • The reproduction number had three peaks that came several days before the surge in COVID-19 cases. • There was a strong negative correlation between the kinematic viscosity of atmospheric air and the reproduction number. • One influencing factor is air temperature, which means the winter season could have an effect on viral transmission., Background The large number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has plunged the world into fear in recent times. In Japan, 18,769 novel coronavirus disease 2019 (COVID-19) cases have been reported as of June 30, 2020. This study aimed to assess whether cluster infection prevention is possible by evaluating the association between viral transmission and meteorological factors. Methods This study included 1263 people who were successively diagnosed with COVID-19 in Hokkaido, Japan between January 24, 2020 and June 30, 2020. After obtaining the values from the Japanese Meteorological Agency, the average scores of air temperature and humidity were calculated and compared with COVID-19 reproduction numbers, and the association between COVID-19 incidence or reproduction number and meteorological factors was assessed. Results The COVID-19 reproduction number in Hokkaido had three peaks that came several days before the surge in COVID-19 cases. The peaks are indicative of cluster infections. There was a strong negative correlation between the kinematic viscosity of atmospheric air and the reproduction number. Discussion and Conclusion Analysis of the reproduction number is important for predicting or suppressing COVID-19 infection clusters. The authors found a strong association between meteorological factors, such as kinematic viscosity of atmospheric air and the incidence of COVID-19 infection. Meteorological forecasts could provide foreknowledge about COVID-19 infection clusters in the future.

Background Monopharmacy with antipsychotics and antidepressants is the first-line treatment for schizophrenia and major depressive disorder (MDD) in most clinical guidelines, while polypharmacy with psychotropic agents in the treatment of schizophrenia is common in clinical practice. There are no detailed data on the prescription patterns for inpatients with mental illness with reliable diagnoses made by treating psychiatrists. Methods We gathered prescription data at discharge from 2177 patients with schizophrenia and 1238 patients with MDD from October 2016 to March 2018. Results The patients with schizophrenia aged between 60 and 79 were prescribed lower doses of antipsychotics and hypnotics/anxiolytics than those aged between 40 and 59. There were significant differences between the prescription rate of antipsychotics in the patients with schizophrenia and that of antidepressants in the patients with MDD. The frequency of concomitant drugs such as anti-Parkinson drugs, anxiolytics/hypnotics and mood stabilizers in the subjects with schizophrenia prescribed antipsychotic polypharmacy was significantly higher than that with monotherapy. For the patients with schizophrenia, olanzapine, risperidone, aripiprazole, quetiapine, and blonanserin were the five most prescribed antipsychotics. For the patients with MDD, mirtazapine, duloxetine, escitalopram, trazodone and sertraline were the five most prescribed antidepressants. Conclusions Our results showed the use of high doses of antipsychotics, high percentages of antipsychotic polypharmacy and concurrent use of hypnotics/anxiolytics in patients with schizophrenia. Notably, these data were collected before intensive instruction regarding the guidelines; therefore, we need to assess the change in the prescription pattern post guideline instruction.

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

The objective of the present study was to formulate and evaluate transdermal patch of Blonanserin. Blonanserin transdermal patches were prepared by solvent casting method using natural and synthetic polymer. Various plastisizer were screened along with polymers. Drug excipient compatibility studies concluded that the drug and excipient are compatible with each other. The prepared patches were evaluated for physico-chemical parameters to justify their suitability for transdermal use. Formulations containing Xanthan Gum with plasticizer propylene glycol gives best drug release in 8 hours. More than 90% drug release found after 8 hours in formulation F5. Hence F5 formulation is considered as optimized batch. F5 batch was found stable during stability study. Blonanserin transdermal patches were successfully prepared by solvent casting method using Xanthan Gum natural polymer.

Background Blonanserin transdermal patch therapy is now available in Japan for the treatment of schizophrenia and may provide several advantages over the tablet formulation. Objective The aim was to evaluate the long-term safety and efficacy of blonanserin transdermal patches in Japanese patients with schizophrenia. Methods An open-label study was conducted in adults with schizophrenia at 37 sites in Japan. Patients were enrolled in either cohort 1 or 2. Patients in cohort 1 received 8–16 mg/day blonanserin tablets for 6 weeks and then 40–80 mg/day blonanserin patches for 52 weeks. The dose of blonanserin patches was determined according to the dose of the tablets. In cohort 2, every patient started from 40 mg/day and then 40–80 mg/day blonanserin transdermal patches for 52 weeks. Both cohorts had 1–2 weeks of follow-up. Safety endpoints included the incidence of adverse events (AEs), treatment-related AEs, extrapyramidal AEs [also assessed using the change in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) score], the use of any concomitant antiparkinsonian drugs, and skin-related AEs, including skin irritation. Patients also underwent assessment of laboratory values including for serum prolactin concentration, vital signs, body weight, electrocardiographic (ECG) changes, and the corrected QT (QTc) interval. Suicidal ideation was assessed via the Columbia-Suicide Severity Rating Scale (C-SSRS) score. Efficacy was assessed via duration of blonanserin transdermal patch treatment, Positive and Negative Syndrome Scale (PANSS) total and subscale scores, and Clinical Global Impression-Severity (CGI-S) scores. Other endpoints included total Drug Attitude Inventory 10 (DAI-10) scores, EuroQol-5 Dimension (EQ-5D) effect values, and a patient questionnaire about the dosage form. Results A total of 223 patients with consents, 117 in cohort 1 and 106 in cohort 2 were included in the study. Of the 117 patients in cohort 1, 108 were treated with blonanserin tablets, and 97 received blonanserin patches and were included in the safety analysis set. In cohort 2, 103 of the 106 patients were treated with blonanserin transdermal patches and were included in the safety analysis set. In total, 91 patients were male (45.5%). The mean age was 43.8 years. Discontinuation occurred in 40 patients (41.2%) in cohort 1 and 44 patients (42.7%) in cohort 2. Discontinuation resulted from AEs in 18.6% (cohort 1) and 11.7% (cohort 2) and from withdrawal of consent in 13.4% (cohort 1) and 20.4% (cohort 2), and seven patients overall discontinued due to skin reactions. AEs were reported in 174 patients (87.0%), and 13 serious AEs occurred in 12 patients (6.0%), of which six patients were in cohort 1 and six patients were in cohort 2. Serious AEs were six schizophrenia (n = 6) and seven other AEs (n = 6), which included impulse-control disorder, fracture, epistaxis, asthma, pneumonia aspiration, pneumonia hemophilus, and pneumonia. The most common AEs were nasopharyngitis (n = 62, 31.0%), application site erythema (n = 45, 22.5%), application site pruritus (n = 23, 11.5%), and akathisia (n = 20, 10.0%). AE incidence was similar in cohort 1 (84.5%) and cohort 2 (89.3%). Extrapyramidal and skin-related AEs were reported in 51 patients (25.5%) and 83 patients (41.5%), respectively. None of these AEs were serious. The mean change from baseline in total DIEPSS score at Week 52 {last observation carried forward [LOCF] (standard deviation [SD])} was −0.1 (1.55), indicating no marked effect. In terms of concomitant medications used in cohort 1 and cohort 2, 33.0% (32/97) and 22.3% (23/103) used antiparkinsonian drugs, respectively. The majority of skin-related AEs occurred early in treatment and were appropriately managed with topical therapies. Of the patients who answered “No” to all C-SSRS categories at baseline (n = 129), 13 patients (10.1%) were evaluated as having emergence of suicidal ideation. Among patients who answered “No” to all C-SSRS suicidal behavior categories at baseline (n = 172), one (0.6%) was evaluated as having suicidal behavior during blonanserin transdermal patch treatment. There were no clinically significant changes in laboratory tests or examinations, including prolactin level, vital signs, body weight, ECG, metabolism-related parameters, and QTc interval. The mean (SD) change in body weight was − 0.04 (4.561) kg and − 0.67 (6.841) kg in cohort 1 and cohort 2, respectively. The mean changes from baseline in PANSS total score at Week 52 (LOCF [SD]) were − 0.1 [11.6] and − 3.4 [15.3] in cohort 1 and 2, respectively. PANSS scores did not change after switching from tablet to patch formulation in cohort 1 and decreased over the 52 weeks of treatment with the blonanserin patches. The mean change from baseline in CGI-S score at Week 52 (LOCF [SD]) was − 0.2 [1.03] in both cohorts combined. After 52 weeks of blonanserin patch treatment, the total DAI-10 score increased or remained unchanged compared with baseline in 82 of the 129 patients (63.6%) for whom these data were available. In the intention-to-treat population of the combined cohorts (n = 200), the mean (SD) change from baseline in EQ-5D score at the last assessment was − 0.0365 (0.17603). Patients’ attitudes to the blonanserin transdermal patches were generally positive. Conclusions Blonanserin transdermal patches are safe and effective in the long-term treatment of schizophrenia. ClinicalTrials.gov registration NCT02335658. Electronic supplementary material The online version of this article (10.1007/s40263-019-00692-6) contains supplementary material, which is available to authorized users.

Objective To report the efficacy and safety of blonanserin in patients with schizophrenia compared with risperidone in a Japanese multicenter, randomized, double‐blind study based on post hoc sensitivity analysis in addition to the previous results reported by Miura and discuss the current approaches for schizophrenia treatment. Methods Of 302 patients randomized, 156 received blonanserin (8‐24 mg/d) and 145 received risperidone (2‐6 mg/d) for 8 weeks. Efficacy variables included the Positive and Negative Syndrome Scale (PANSS) total score for the primary outcome, PANSS subscale, Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression‐Improvement (CGI‐I) for secondary outcomes. Safety variables included treatment‐emergent adverse events, Drug Induced Extrapyramidal Symptoms Scale scores, laboratory data, vital signs, electrocardiogram, etc Results Blonanserin was not inferior to risperidone in the change in PANSS total score at a non‐inferior margin of −7 (intergroup difference, −0.46; 95% CI, −4.40 to 3.48). Post hoc analyses wholly supported the primary result. No major difference was found in the changes in BPRS scores and the improvement rate on CGI‐I between the drugs. The incidence of adverse events was similar in the two drugs. Blonanserin was associated with a lower risk of prolactin increase, weight gain, and orthostatic hypotension compared with risperidone. However, blonanserin was associated with a higher incidence of akathisia and excitability compared with risperidone. Most of the adverse events were mild to moderate in severity with no specific events of predominant high severity in the both drugs. Conclusions Blonanserin exerted the similar efficacy to risperidone in both positive and negative symptoms in schizophrenia with a lower risk of prolactin increase, weight gain, and orthostatic hypotension compared with risperidone. Blonanserin will serve as a favorable treatment option for schizophrenia in daily clinical practice., Blonanserin exerted the similar efficacy in both positive and negative symptoms in schizophrenia and similar well‐tolerable safety profiles with minor variation compared with risperidone. Further investigation is needed to clarify the potential benefit of blonanserin in the context of the latest schizophrenia treatment.

Blonanserin differs from other antipsychotic drugs, such as risperidone and olanzapine, and exhibits a higher affinity for dopamine-D2/3 receptors than for serotonin 5-HT2A receptors. We investigated the involvement of dopamine-D3 receptors in the effect of blonanserin on the social deficit observed in an animal model of schizophrenia and sought to elucidate the molecular mechanism underlying its action. Mice received phencyclidine (PCP: 10 mg/kg/day, s.c.), a non-competitive N-methyl- d -aspartate (NMDA) receptor antagonist, once a day for 14 consecutive days. We then evaluated the sociability, using a social interaction test, and the expression of GluN1 subunit, an essential subunit of the NMDA receptors, in these mice. Blonanserin significantly ameliorated the PCP-induced social deficit, whereas olanzapine and haloperidol did not. This effect of blonanserin was antagonized by 7-OH-DPAT, a dopamine-D3 receptor agonist, and SCH23390, a dopamine-D1 receptor antagonist. However, the ameliorating effect of blonanserin was not inhibited by DOI, a serotonin 5-HT2A receptor agonist. The PCP-induced social deficit was also ameliorated by U99194, a dopamine-D3 receptor antagonist and SKF38393, a dopamine-D1 receptor agonist, being effects antagonized by 7-OH-DPAT or SCH23390. Blonanserin significantly inhibited the decrease in the phosphorylation levels of GluN1 at Ser897 by protein kinase A (PKA) in the prefrontal cortex (PFC) in PCP administered mice. These results suggest that activation of NMDA receptors due to Ser897-phosphorylation of GluN1 subunit, which is a step linked to dopamine-D1 receptor-PKA signaling through dopamine-D3 receptor antagonism in the PFC, is required for the ameliorating effect of blonanserin on the PCP-induced social deficit. These findings also provide in vivo evidence that blonanserin antagonism of the dopamine-D3 receptors may be useful as a novel treatment strategy and that the dopamine-D3 receptors can be a novel therapeutic target molecule for the social deficit observed in schizophrenia.

Purpose: The objective of this retrospective chart review study was to evaluate the long-term efficacy and tolerability of blonanserin treatment in individuals with schizophrenia. Patients and methods: We collected data from 28 (56%) antipsychotic-naïve subjects with first-episode (FE) schizophrenia and 22 subjects with relapsed schizophrenia treated with blonanserin. We investigated psychiatric hospitalization and medication discontinuation rates, Positive and Negative Syndrome Scale (PANSS) scores, Clinical Global Impression–Severity (CGI-S) scale scores, body mass index (BMI) at baseline to endpoint and laboratory tests including serum prolactin, total cholesterol (TC), low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides (TG), and glucose. Additionally, we measured the differences between the two groups and overall changes in levels. Results: Thirty-one subjects received blonanserin for 3 years. Significant improvements in psychiatric symptoms from baseline to endpoint were observed individuals with schizophrenia who received blonanserin treatment. There were remarkable changes in PANSS and CGI-S scores between baseline and those measured after 3 years (p .05) in both groups. After 3 years of treatment, there was a statistically significant increase in TC and TG with only a minimal increase in BMI (p

Antipsychotics are often the first-line treatment for behavioral and psychological symptoms of dementia. However, the potential anticholinergic effects of antipsychotics could counteract the therapeutic effects of cholinesterase inhibitors used to treat dementia. We investigated the inhibitory effects of 26 antipsychotics on [N-Methyl-3H]scopolamine specific binding in mouse cerebral cortex. At 10−5 M, chlorpromazine, levomepromazine, prochlorperazine, timiperone, zotepine, pimozide, blonanserin, olanzapine, quetiapine, and clozapine inhibited [N-Methyl-3H]scopolamine binding by > 45%. Furthermore, the pKi values of chlorpromazine, levomepromazine, zotepine, olanzapine, and clozapine overlapped with their clinically achievable blood concentrations. Therefore, the anticholinergic properties of these antipsychotics could attenuate the effects of cholinesterase inhibitors. Keywords: Antipsychotics, Anticholinergic effect, Mouse cerebral cortex

Objective This Japanese, multicenter, randomized, double‐blind trial, evaluating the efficacy and safety of blonanserin compared with haloperidol in patients with schizophrenia, was previously published by Murasaki in the Japanese language. In this article, we present the results of the trial based on full analysis dataset instead of per protocol dataset formerly reported and discuss the findings in light of the latest knowledge of pharmacological treatment for schizophrenia. Methods A total of 265 patients were randomized to receive blonanserin (8 to 24 mg/d) or haloperidol (4 to 12 mg/d) twice daily for 8 weeks. Efficacy assessments included the Clinical Global Impressions—Improvement (CGI‐I) and the Positive and Negative Syndrome Scale (PANSS). Results Blonanserin was not inferior to haloperidol with a margin of 10% with respect to the improvement rate on CGI‐I at end of study (60.5% vs 50.0%, P, Blonanserin is as effective as haloperidol for the treatment of schizophrenia. Blonanserin is more effective for negative symptoms with a lower risk of extrapyramidal symptoms compared with haloperidol. Blonanserin is considered an appropriate antipsychotic drug to combine with cognitive remediation therapy.

Background There has been number of studies suggesting experiences of adversity in early life interrelated subsequent brain development, however, neurobiological mechanisms confer risk for onset of psychiatric illness remains unclear. Methods In order to elucidate the pathogenic mechanisms underlying early life adversity-induced refractory depression in more detail, we administered corticosterone (CORT) to adolescent rats with or without prenatal ethanol exposure followed by an antidepressant or antipsychotic and examined alterations in depressive and social function behaviors and brain-derived neurotrophic factor (BDNF) levels in serum, the hippocampus, anterior cingulate cortex, and nucleus accumbens. Results The combined stress exposure of prenatal ethanol and adolescent CORT prolonged immobility times in the forced swim test (FST), and increased investigation times and numbers in the social interaction test (SIT). A treatment with escitalopram reversed depression-like behavior accompanied by reductions in BDNF levels in serum and the nucleus accumbens, while a treatment with blonanserin ameliorated abnormal social interaction behavior with reductions in serum BDNF levels. Limitations Further studies are needed to clarify the clinical evinces responding to these results, and many questions remain regarding the mechanisms by which refractory depression and antidepressant/antipsychotic treatments cause changes in serum and brain regional BDNF levels. Conclusion These results strongly implicate changes in BDNF levels in serum and the nucleus accumbens in the pathophysiology and treatment of early life combined stress-induced depression and highlight the therapeutic potential of escitalopram and new generation antipsychotic blonanserin for treatment-resistant refractory depression.

Background 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. Methods 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. Results 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. Conclusion Our results are similar to those of previous network meta-analysis involving various races and ethnicities.