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Background: We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of blonanserin and risperidone for the treatment of schizophrenia and to provide reliable pharmacotherapeutic evidence for in the clinical treatment of schizophrenia., Methods: We systematically searched the PubMed, Cochrane Library, Embase, Chinese Biomedical Literature Database (CBM), and China National Knowledge Infrastructure (CNKI) databases for head-to-head randomized controlled trials that compared blonanserin with risperidone for the treatment of schizophrenia. We extracted the following data: author, year, country, diagnostic criteria, sample size, course of treatment, dosage and outcomes. Our main endpoint was the changes in the Positive and Negative Syndrome Scale (PANSS) total scores. Meta-analysis of the included data was conducted by RevMan 5.3 software. We used the GRADE criteria to evaluate the certainty of the evidence., Results: A total of 411 studies were initially; 8 trials were eligible and were included in our analysis (N = 1386 participants). Regarding efficacy, there was no difference in changes in the PANSS total scores between the two groups (P > 0.05). In terms of safety, compared to risperidone, the incidence of serum prolactin increases and weight gain in the blonanserin group was lower (P<0.05), but the incidence of extrapyramidal symptoms (EPS) was higher (P<0.05)., Conclusion: The efficacy of blonanserin is similar to that of risperidone, but it is unclear whether blonanserin is more effective than risperidone at improving cognitive and social function. More high-quality studies are needed to verify the efficacy and safety of blonanserin in the future., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Hyperprolactinemia and metabolic disturbance are common side effects of antipsychotics that cause intolerance. Despite its potential influence on relapse, there are no established guidelines for antipsychotic switching. This naturalistic study explored the association between antipsychotic switching, baseline clinical status, metabolic changes, and relapse in patients with schizophrenia. In total, 177 patients with amisulpride-induced hyperprolactinemia and 274 with olanzapine-induced metabolic disturbance were enrolled. Relapse was determined by assessing changes in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to 6 months (increased over 20% or 10% reaching 70). Metabolic indices were measured at baseline and 3 months. Patients with baseline PANSS >60 were more likely to relapse. Further, patients switching to aripiprazole had a higher risk of relapse regardless of their original medication. Participants who originally used amisulpride had reduced prolactin levels following medication change, while switching to olanzapine caused increased weight and blood glucose levels. In patients originally using olanzapine, only switching to aripiprazole reduced insulin resistance. Adverse effects on weight and lipid metabolism were observed in patients who switched to risperidone, while amisulpride improved lipid profiles. Changing schizophrenia treatment requires careful consideration of multiple variables, particularly the choice of substituted drug and the patient's baseline symptoms., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: A post-marketing surveillance of blonanserin has been ongoing since September 2018. The aim of this study was to assess the effectiveness and safety of oral blonanserin in Chinese young and middle-aged female patients with schizophrenia in real clinical settings, using the data from the post-marketing surveillance., Methods: A 12-week, prospective, multi-center, open-label, post-marketing surveillance was conducted. Female patients aged 18-40 years were included in this analysis. The Brief Psychiatric Rating Scale (BPRS) was used to evaluate the effectiveness of blonanserin in improving psychiatric symptoms. The incidence of adverse drug reactions (ADRs) such as of extrapyramidal symptoms (EPS), prolactin elevation and the weight gain were used to evaluate the safety profile of blonanserin., Results: A total of 392 patients were included both in the safety and full analysis sets, 311 patients completed the surveillance protocol. The BPRS total score was 48.8 ± 14.11 at the baseline, decreasing to 25.5 ± 7.56 at 12 weeks (P < 0.001, compared with baseline). EPS (20.2%) including akathisia, tremor, dystonia, and parkinsonism were found as the most frequent ADRs. The mean weight gain was 0.27 ± 2.5 kg at 12 weeks from the baseline. Four cases (1%) of prolactin elevation were observed during the period of surveillance., Conclusion: Blonanserin significantly improved the symptoms of schizophrenia in female patients aged 18-40 years; the drug was well tolerated and had a low tendency to cause metabolic side effects, including prolactin elevation in these patients. Blonanserin might be a reasonable drug for the treatment of schizophrenia in young and middle-aged female patients., (© 2023. The Author(s).)

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, multicenter, open-label extension study enrolled adolescent patients with schizophrenia who opted to enter in this study after the completion of the preceding placebo-controlled study. Blonanserin tablet was orally administered twice daily, after morning and evening meals, for 52 weeks using dose-titration method within a range between 4 and 24 mg/day. The primary end point was the change from baseline to the end of the study in the Positive and Negative Syndrome Scale (PANSS) total score. Safety/tolerability was assessed by the incidence and severity of adverse events. Results: Of 117 patients who completed the preceding placebo-controlled study, 109 entered this extension study and 43 (39.4%) of them discontinued the study treatment. The safety analysis set comprised 106 patients who received the study drug at least once, including 36 and 70 patients treated with placebo (DB-placebo group) and blonanserin tablet (DB-blonanserin group), respectively, in the placebo-controlled study. At the last assessment, the mean change in PANSS total score overall [mean (standard deviation)] was -24.9 (20.76) from the baseline of the placebo-controlled study, which was similar in the DB-placebo and DB-blonanserin groups. The overall incidence of adverse events was 90.6%, and most of them were mild or moderate in severity, with similar incidence of extrapyramidal symptoms (38.7%) to that in adults receiving long-term blonanserin oral tablet treatment and minimal change in weight and metabolic parameters. Conclusions: This long-term extension study showed that 52 weeks of oral blonanserin treatment improved or stabilized psychiatric symptoms in patients with adolescent schizophrenia. There were no major issues with the safety or tolerability of blonanserin administration in this study. Considering relatively less adverse effects on weight increase and metabolic parameters, blonanserin is expected to be a safe/tolerable treatment option for adolescent schizophrenia that can be used seamlessly from adolescence to adulthood.

Rationale: Unlike other antipsychotics, our previous positron emission tomography (PET) study demonstrated that a single dose of blonanserin occupied dopamine D 3 as well as dopamine D 2 receptors in healthy subjects. However, there has been no study concerning the continued use of blonanserin., Objectives: We examined D 2 and D 3 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. D 2 and D 3 receptor occupancies were evaluated by [ 11 C]-(+)-PHNO. We used nondisplaceable binding potential (BP ND ) of 6 healthy subjects which we previously reported as baseline. To consider the effect of upregulation of D 3 receptor by continued use of antipsychotics, D 3 receptor occupancy by blonanserin in seven subjects who completed 2 PET scans were re-analyzed by using BP ND 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%. EC 50 was 0.30 ng/mL for D 2 receptor for caudate and putamen (df = 19, p < 0.0001) and 0.70 ng/mL for D 3 receptor for globus pallidus and substantia nigra (df = 19, p < 0.0001). EC 50 for D 3 receptor of blonanserin changed to 0.22 ng/mL (df = 13, p = 0.0041) when we used BP ND of olanzapine condition as baseline., Conclusions: Our study confirmed that blonanserin occupied both D 2 and D 3 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 <65 years) with schizophrenia (DSM-IV-TR criteria; total Positive and Negative Syndrome Scale score <120 at screening) treated with blonanserin 8-mg or 16-mg tablets. Patients continued tablets for 2-4 weeks at their current dose and were then assigned to once-daily blonanserin patches (10/20/40/60/80 mg daily) for 2-4 weeks based on the oral dose. [11C]raclopride positron emission tomography scanning determined blonanserin striatal dopamine D2 receptor occupancy (primary endpoint). Secondary endpoints included assessment of receptor occupancy by dose, changes in Positive and Negative Syndrome Scale and Clinical Global Impressions-Severity of Illness-Severity scores, patient attitudes towards adherence, and patch adhesiveness., 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)., (© The Author(s) 2020. Published by Oxford University Press on behalf of CINP.)

Schizophrenia significantly limits social functioning with positive and negative symptoms and cognitive dysfunction. Blonanserin (LONASEN®), a novel second-generation antipsychotic approved for treating schizophrenia in Japan in 2008, reportedly shows beneficial effects on cognitive function as well as positive and negative symptoms, with potential for improving social functioning. To understand the safety and effectiveness of blonanserin in the real clinical practice, five Japanese post-marketing surveillances have been conducted and published to date. In this article, we reviewed all the Japanese post-marketing surveillances and discussed the clinical usefulness of blonanserin in patients with schizophrenia having diverse clinical characteristics. Adverse drug reactions, such as akathisia and extrapyramidal symptoms, were common in all surveillances. However, those specific to second-generation antipsychotics, such as weight gain and abnormalities in glycometabolism or lipid metabolism, were rarely observed. In addition, no adverse drug reactions apart from clinical trial results were found. Brief Psychiatric Rating Scale total scores in all surveillances significantly lowered at the last evaluation than at baseline. These results were consistent through 1-year of treatment, suggesting that effectiveness is maintained even after long-term use. In conclusion, blonanserin is considered a beneficial drug in real clinical practice for patients with schizophrenia having diverse characteristics., Competing Interests: Declaration of competing interest All the authors are employees of Sumitomo Dainippon Pharma Co, Ltd. The authors report no other conflicts of interest related to this work., (Copyright © 2020 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Dopamine supersensitivity psychosis (DSP) is a key factor contributing to the development of antipsychotic treatment-resistant schizophrenia. We examined the efficacy and safety of blonanserin (BNS) and olanzapine (OLZ) as adjuncts to prior antipsychotic treatment in patients with schizophrenia and DSP in a 24-week, multicenter (17 sites), randomized, rater-blinded study with two parallel groups (BNS and OLZ add-on treatments) in patients with schizophrenia and DSP: the ROADS Study. The primary outcome was the change in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 24. Secondary outcomes were changes in the PANSS subscale scores, Clinical Global Impressions, and Extrapyramidal Symptom Rating Scale (ESRS), and changes in antipsychotic doses. The 61 assessed patients were allocated into a BNS group (n = 26) and an OLZ group (n = 29). The PANSS total scores were reduced in both groups (mean ± SD: -14.8 ± 24.0, p = 0.0042; -10.5 ± 12.9, p = 0.0003; respectively) with no significant between-group difference (mean, -4.3, 95 %CI 15.1-6.4, p = 0.42). The BNS group showed significant reductions from week 4; the OLZ group showed significant reductions from week 8. The ESRS scores were reduced in the BNS group and the others were reduced in both groups. The antipsychotic monotherapy rates at the endpoint were 26.3 % (n = 6) for BNS and 23.8 % (n = 5) for OLZ. The concomitant antipsychotic doses were reduced in both groups with good tolerability. Our results suggest that augmentations with BNS and OLZ are antipsychotic treatment options for DSP patients, and BNS may be favorable for DSP based on the relatively quick responses to BNS observed herein., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

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., (© 2019 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Society of NeuropsychoPharmacology.)

This study examined randomized controlled trial data for blonanserin and risperidone in Chinese schizophrenia patients (N = 264). Data related to historical changes in the Positive and Negative Syndrome Scale (PANSS) were used to successfully construct a longitudinal E max model. Results: (a) The efficacy of the two drugs was similar after week 8, showing a small difference in PANSS reduction. (b) Using the model, we predicted that each 5-point increase in the baseline FPOS (positive score in PANSS five-factor subscales) leads to a decrease in the PANSS total scores at week 8 for 2 points in patients administered blonanserin. (c) The effect of blonanserin on prolactin (PRL) elevation was less. The model was used to predict that prolactin elevations in patients administered risperidone were 2.41-fold of those in patients administered blonanserin. (d) Model quantitation showed that gender is a risk factor for prolactin elevation. Prolactin elevations in female patients were 2.95-fold of the value in male patients administered the same drug. The model demonstrated Blonanserin has similar antischizophrenic efficacy and less serum prolactin rising compared to risperidone in Chinese patients., (© 2019 John Wiley & Sons, Ltd.)

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 < 0.001). The decrease in the PANSS total score did not differ between the drugs (-10.3 vs -7.1). For the PANSS negative symptom score, the decrease was significantly greater with blonanserin than with haloperidol (P = 0.006). Blonanserin was well tolerated. The incidence of adverse events was similar for the two drugs. Extrapyramidal adverse events, sedation, hypotension, and prolactin increase were rarer with blonanserin than with haloperidol. No clinically important weight gain was observed., Conclusions: 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., (© 2019 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Blonanserin differs from other antipsychotic drugs, such as risperidone and olanzapine, and exhibits a higher affinity for dopamine-D 2/3 receptors than for serotonin 5-HT 2A receptors. We investigated the involvement of dopamine-D 3 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-D 3 receptor agonist, and SCH23390, a dopamine-D 1 receptor antagonist. However, the ameliorating effect of blonanserin was not inhibited by DOI, a serotonin 5-HT 2A receptor agonist. The PCP-induced social deficit was also ameliorated by U99194, a dopamine-D 3 receptor antagonist and SKF38393, a dopamine-D 1 receptor agonist, being effects antagonized by 7-OH-DPAT or SCH23390. Blonanserin significantly inhibited the decrease in the phosphorylation levels of GluN1 at Ser 897 by protein kinase A (PKA) in the prefrontal cortex (PFC) in PCPadministered mice. These results suggest that activation of NMDA receptors due to Ser 897 -phosphorylation of GluN1 subunit, which is a step linked to dopamine-D 1 receptor-PKA signaling through dopamine-D 3 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-D 3 receptors may be useful as a novel treatment strategy and that the dopamine-D 3 receptors can be a novel therapeutic target molecule for the social deficit observed in schizophrenia., (Copyright © 2019. Published by Elsevier Ltd.)

Objective: Dopamine supersensitivity psychosis (DSP) is one of the key factors contributing to the development of antipsychotic treatment-resistant schizophrenia (TRS). We investigated the efficacy of blonanserin, an atypical antipsychotic, for patients with TRS and DSP., Methods: In this 12-month retrospective follow-up study, we investigated the cases of eight consecutive patients with unstable TRS and DSP treated with blonanserin as an add-on therapy. We examined changes in scores for the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression-Severity of Illness (CGI-S) scale and the Global Assessment of Functioning scale (GAF) during the 12 months after the administration of blonanserin., Results: The patients' total scores on the BPRS and GAF scores were significantly improved by 3 months at the latest. Positive BPRS and CGI-S scores were also improved by 6 months at the latest. The total chlorpromazine-equivalent doses of antipsychotics were significantly reduced from 1462.3±499.6mg to 794.1±642.8mg (p=0.001) after 12 months of blonanserin treatment, with a favorable safety and tolerability profile., Conclusions: Blonanserin may be a promising antipsychotic for the treatment of TRS and DSP., (Copyright © 2016 Elsevier B.V. All rights reserved.)

This randomized, double-blind study compared the efficacy and safety of blonanserin and risperidone to treat Chinese schizophrenia patients aged ≥18 and < 65 years. Patients with Positive and Negative Syndrome Scale (PANSS) total scores ≥70 and ≤ 120 were randomized to receive blonanserin or risperidone using a gradual dose-titration method (blonanserin tablets: 8-24 mg/day; risperidone tablets: 2-6 mg/day), twice daily. Treatment populations consisted of 128 blonanserin-treated patients and 133 risperidone-treated patients. Intention-to-treat analysis was performed using the last observation carried forward method. Reductions of PANSS total scores by blonanserin and risperidone treatment were -30.59 and -33.56, respectively. Risperidone treatment was associated with elevated levels of serum prolactin (67.16% risperidone versus 52.31% blonanserin) and cardiac-related abnormalities (22.39% risperidone versus 12.31% blonanserin), and blonanserin patients were more prone to extrapyramidal side effects (48.46% blonanserin versus 29.10% risperidone). In conclusion, blonanserin was as effective as risperidone for the treatment of Chinese patients with schizophrenia. The overall safety profiles of these drugs are comparable, although blonanserin was associated with a higher incidence of EPS and risperidone was associated with a higher incidence of prolactin elevation and weight gain. Thus, blonanserin is useful for the treatment of Chinese schizophrenia patients., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: The purpose of this study was to evaluate the long-term effectiveness and safety of blonanserin, a second-generation antipsychotic drug developed in Japan, in patients with first-episode schizophrenia., Methods: Twenty-three antipsychotic-naïve patients with first-episode schizophrenia were treated within an open-label, 1-year, prospective trial of blonanserin (2-24 mg/day). Clinical evaluations were conducted at baseline and 2, 6, and 12 months after the start of treatment. The main outcome measures were changes in subjective well-being and subjective quality of life, as assessed by the Subjective Well-being under Neuroleptic treatment scale Short form-Japanese version and the Schizophrenia Quality of Life Scale-Japanese version, respectively. Secondary outcome measures included the Positive and Negative Syndrome Scale, the Brief Assessment of Cognition in Schizophrenia-Japanese version, laboratory tests, bodyweight, and extrapyramidal symptoms., Results: Fourteen patients (60.9%) remained on the study at 1 year. In the intention-to-treat analysis, significant improvements were observed in several subscales on the Subjective Well-being under Neuroleptic treatment scale Short form-Japanese version, the Schizophrenia Quality of Life Scale-Japanese version, and the Brief Assessment of Cognition in Schizophrenia-Japanese version, and in all factor scores on the Positive and Negative Syndrome Scale. Improvement in depressive symptoms with blonanserin treatment was positively correlated with improvements in subjective well-being and subjective quality of life, as well as verbal memory. No significant changes were noted for any safety measure during the 1-year study period., Conclusions: Blonanserin was well tolerated and effective for the treatment of first-episode schizophrenia in terms of subjective wellness, cognition, and a wide range of pathological symptoms. Further large-scale studies are warranted to confirm our findings., (© 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.)

Objective: Blonanserin is a novel atypical antipsychotic drug that has efficacy equal to risperidone. We investigated the effects of aripiprazole and blonanserin on clinical symptoms and plasma levels of homovanillic acid (pHVA) and 3-methoxy-4hydroxyphenylglycol in the switching strategy of schizophrenia., Methods: Twenty two Japanese patients with schizophrenia were enrolled into this open study. The antipsychotics of all patients were switched to aripiprazole or blonanserin for the improvement of clinical symptoms or side effects. Plasma monoamine metabolites levels were analyzed with high-performance liquid chromatography., Results: There were no significant effects for time (p = 0.346) or time × group interaction (p = 0.27) on the changes of positive and negative syndrome scale (PANSS) total score, although blonanserin decreased PANSS scores. We observed negative correlation between pHVA at baseline and the change in PANSS total score (rs = -0.450, p = 0.046). We also found positive correlation between the changes in pHVA and the changes in PANSS total (rs = 0.536, p = 0.015) and positive (rs = 0.572, p = 0.008) scores., Conclusions: There were no differences between blonanserin and aripiprazole in the improvement of clinical symptoms. Our results suggest that pHVA may be useful indicator for the switching strategy to aripiprazole or blonanserin in schizophrenia., (Copyright © 2014 John Wiley & Sons, Ltd.)

Abstract Background We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of blonanserin and risperidone for the treatment of schizophrenia and to provide reliable pharmacotherapeutic evidence for in the clinical treatment of schizophrenia. Methods We systematically searched the PubMed, Cochrane Library, Embase, Chinese Biomedical Literature Database (CBM), and China National Knowledge Infrastructure (CNKI) databases for head-to-head randomized controlled trials that compared blonanserin with risperidone for the treatment of schizophrenia. We extracted the following data: author, year, country, diagnostic criteria, sample size, course of treatment, dosage and outcomes. Our main endpoint was the changes in the Positive and Negative Syndrome Scale (PANSS) total scores. Meta-analysis of the included data was conducted by RevMan 5.3 software. We used the GRADE criteria to evaluate the certainty of the evidence. Results A total of 411 studies were initially; 8 trials were eligible and were included in our analysis (N = 1386 participants). Regarding efficacy, there was no difference in changes in the PANSS total scores between the two groups (P > 0.05). In terms of safety, compared to risperidone, the incidence of serum prolactin increases and weight gain in the blonanserin group was lower (P

Abstract Background Blonanserin (BNS) had been undergoing post-market surveillance (PMS) since September 2018. Using the surveillance data, we did this analysis to assess the safety and effectiveness of different doses of BNS to explore a sufficient dose range of BNS in Chinese patients with schizophrenia (SZ). Methods A 12-week, prospective, observational, single-arm, multicenter, open-label PMS was conducted. In this analysis, we divided the patients from PMS into low, medium to high, and high dose groups based on the dose of BNS they received, with medium to high dose group being the focus. The Brief Psychiatric Rating Scale (BPRS) scores at week 2 or 4, 6 or 8, and 12 were calculated to evaluate the effectiveness of BNS in improving psychiatric symptoms. The safety of BNS was reported as the incidence of adverse drug reactions. Results 364 patients were included in the medium to high dose group, of which 321 completed the surveillance, with a dropout rate of 11.8%. The mean daily dose was 15.1 ± 1.92 mg. The BPRS total score was 50.1 ± 11.95 at baseline and decreased to 26.6 ± 7.43 at 12 weeks (P

Background: Blonanserin (BNS) had been undergoing post-market surveillance (PMS) since September 2018. Using the surveillance data, we did this analysis to assess the safety and effectiveness of different doses of BNS to explore a sufficient dose range of BNS in Chinese patients with schizophrenia (SZ). Methods: A 12-week, prospective, observational, single-arm, multicenter, open-label PMS was conducted. In this analysis, we divided the patients from PMS into low, medium to high, and high dose groups based on the dose of BNS they received, with medium to high dose group being the focus. The Brief Psychiatric Rating Scale (BPRS) scores at week 2 or 4, 6 or 8, and 12 were calculated to evaluate the effectiveness of BNS in improving psychiatric symptoms. The safety of BNS was reported as the incidence of adverse drug reactions. Results: 364 patients were included in the medium to high dose group, of which 321 completed the surveillance, with a dropout rate of 11.8%. The mean daily dose was 15.1 ± 1.92 mg. The BPRS total score was 50.1 ± 11.95 at baseline and decreased to 26.6 ± 7.43 at 12 weeks (P < 0.001). When compared with other groups, the median to high dose group achieved significantly more reduction in BPRS score at week 12 (P = 0.004 versus low dose and P = 0.033 versus higher dose). Extrapyramidal symptoms [EPS (46.4%)] were the most common adverse reactions in the medium to high group. The average weight gain during the surveillance was 0.5 ± 2.56 kg and prolactin elevation occurred in 2.2% patients. Most adverse reactions were mild. Conclusions: BNS at medium to high doses (mean 15.1 mg/d) significantly improved symptoms of SZ and was well-tolerated. Most ADRs were mild, and the likelihood of causing metabolic side effects and prolactin elevations was low. Medium to high dose of BNS is a more potent treatment choice for SZ. Trial registration number: ChiCTR2100048734. Date of registration: 2021/07/15 (retrospectively registered). [ABSTRACT FROM AUTHOR]

The environmental disturbances in a critical neurodevelopmental period exert organizational effects on brain intrinsic plasticity including excitatory and inhibitory (E/I) neurotransmission those can cause the onset of psychiatric illness. We previously reported that treatment of neural precursor cells with N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 induced reduction of GABAergic interneuron differentiation, and these changes recovered by atypical antipsychotic blonanserin treatment in vitro. However, it remains unclear how this treatment affects neural circuit changes in hippocampus and amygdala, which might contribute to the prevention of onset process of schizophrenia. To elucidate the pathogenic/preventive mechanisms underlying prenatal environmental adversity-induced schizophrenia in more detail, we administered poly (I:C) followed by antipsychotics and examined alterations in social/cognitive behaviors, GABA/glutamate-related gene expressions with cell density and E/I ratio, and brain-derived neurotrophic factor (Bdnf) transcript levels, particularly in limbic areas. Treatment with antipsychotic blonanserin ameliorated impaired social/cognitive behaviors and increased parvalbumin (PV)-positive (+) cell density and its mRNA levels as well as Bdnf with long 3′UTR mRNA levels, particularly in the dorsal hippocampus, in rats exposed to maternal immune activation (MIA). Low dose of blonanserin and haloperidol altered GABA and glutamate-related mRNA levels, the E/I ratio, and Bdnf long 3′UTR mRNA levels in the ventral hippocampus and amygdala, but did not attenuate behavioral impairments. These results strongly implicate changes in PV expression, PV(+) GABAergic interneuron density, and Bdnf long 3′UTR expression levels, particularly in the dorsal hippocampus, in the pathophysiology and treatment responses of MIA-induced schizophrenia and highlight the therapeutic potential of blonanserin for developmental stress-related schizophrenia. • Blonanserin (Blon) exerts recovery effect against social dysfunction in developmental adversity caused by MIA.. • Blon also increases Bdnf with long 3' UTR (Bdnf long) mRNA in d-Hip in effective dose. • Lower dose of Blon increases GABA related/Bdnf long genes and decreases E/I ratio in v-Hip, without behavioral effect. • Modulation of PV(+) cells and trophic mechanisms in d-Hip can be expected for therapeutic intervention in schizophrenia. [ABSTRACT FROM AUTHOR]

Abstract Background A post-marketing surveillance of blonanserin has been ongoing since September 2018. The aim of this study was to assess the effectiveness and safety of oral blonanserin in Chinese young and middle-aged female patients with schizophrenia in real clinical settings, using the data from the post-marketing surveillance. Methods A 12-week, prospective, multi-center, open-label, post-marketing surveillance was conducted. Female patients aged 18–40 years were included in this analysis. The Brief Psychiatric Rating Scale (BPRS) was used to evaluate the effectiveness of blonanserin in improving psychiatric symptoms. The incidence of adverse drug reactions (ADRs) such as of extrapyramidal symptoms (EPS), prolactin elevation and the weight gain were used to evaluate the safety profile of blonanserin. Results A total of 392 patients were included both in the safety and full analysis sets, 311 patients completed the surveillance protocol. The BPRS total score was 48.8 ± 14.11 at the baseline, decreasing to 25.5 ± 7.56 at 12 weeks (P

Schizophrenia is an unexplained, complex and serious mental illness. Blonanserin (BNS) is a new antipsychotic drug widely used in the treatment of schizophrenia. However, large-scale clinical studies have not been conducted in China. A multi-center, prospective, open-label, 12-week surveillance was carried out to evaluate the safety and effectiveness of BNS in patients with schizophrenia in China. Safety assessments included adverse drug reactions (ADRs), extrapyramidal symptoms (EPS), akathisia, concomitant medications for EPS by the end of treatment, and the changes in body weight from baseline by the end of treatment. The effectiveness was evaluated by the Brief Psychiatric Rating Scale (BPRS). From September 2018 to May 2020, of the 1,060 patients enrolled, 1,018 were included in the full analysis set (FAS) and safety set (SS), respectively. ADRs were developed in 205 patients among the included, the incidence being 20.1%. ADRs of EPS occurred in 169 patients, the incidence being 16.6%, ADRs of akathisia occurred in 90 patients, the incidence being 8.8%; concomitant therapeutic and prophylactic agents for EPS accounts for 19.2%; 4.0% of patients had a =7% increase in body weight from baseline at 12 weeks after initiating treatment. Using the last-observation-carried-forward (LOCF) method, the changes in total BPRS scores were -11.2 ± 10.17 (N = 1,018), -16.8 ± 12.69 (N = 1,018) and -20.6 ± 13.99 (N = 1,018) after 2/4, 6/8, or 12 weeks, respectively. 53.5% (545/1,018) patients showed response to blonanserin treatment in week 12. The post-marketing surveillance results of BNS demonstrates safety profile and effectiveness of the drug. [ABSTRACT FROM AUTHOR]

Abstract 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.

Schizophrenia significantly limits social functioning with positive and negative symptoms and cognitive dysfunction. Blonanserin (LONASEN®), a novel second-generation antipsychotic approved for treating schizophrenia in Japan in 2008, reportedly shows beneficial effects on cognitive function as well as positive and negative symptoms, with potential for improving social functioning. To understand the safety and effectiveness of blonanserin in the real clinical practice, five Japanese post-marketing surveillances have been conducted and published to date. In this article, we reviewed all the Japanese post-marketing surveillances and discussed the clinical usefulness of blonanserin in patients with schizophrenia having diverse clinical characteristics. Adverse drug reactions, such as akathisia and extrapyramidal symptoms, were common in all surveillances. However, those specific to second-generation antipsychotics, such as weight gain and abnormalities in glycometabolism or lipid metabolism, were rarely observed. In addition, no adverse drug reactions apart from clinical trial results were found. Brief Psychiatric Rating Scale total scores in all surveillances significantly lowered at the last evaluation than at baseline. These results were consistent through 1-year of treatment, suggesting that effectiveness is maintained even after long-term use. In conclusion, blonanserin is considered a beneficial drug in real clinical practice for patients with schizophrenia having diverse characteristics.

Abstract 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.

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]

Blonanserin is a second-generation atypical antipsychotic agent with potent affinity to dopamine D2 and D3 receptors and serotonin 5-HT2 A receptor,and with low or negligible affinity for adrenergic α1,serotonin5-HT2 C,histamine H1,and muscarinic M1 and M3 receptors.It is effective in both positive and negative symptoms of schizophrenia,and improves some domain of the cognitive symptoms and social functions of patients.Based on the evidences and clinical experiences of several Chinese and Japanese experts,the article aimed to provide a comprehensive,objective,and reasonable medication recommendation for clinical psychiatrists and help patients with schizophrenia to recover and return to society at the earliest. [ABSTRACT FROM AUTHOR]

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 <20%. These results indicated that the plasma blonanserin concentration and dopamine D2 receptor occupancy were stable after blonanserin transdermal patch application, which may lead to improved tolerability during the treatment of patients with schizophrenia. [ABSTRACT FROM AUTHOR]

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

Abstract 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

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. [ABSTRACT FROM AUTHOR]

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 <65 years) with schizophrenia (DSM-IV-TR criteria; total Positive and Negative Syndrome Scale score <120 at screening) treated with blonanserin 8-mg or 16-mg tablets. Patients continued tablets for 2–4 weeks at their current dose and were then assigned to once-daily blonanserin patches (10/20/40/60/80 mg daily) for 2–4 weeks based on the oral dose. [11C]raclopride positron emission tomography scanning determined blonanserin striatal dopamine D2 receptor occupancy (primary endpoint). Secondary endpoints included assessment of receptor occupancy by dose, changes in Positive and Negative Syndrome Scale and Clinical Global Impressions-Severity of Illness-Severity scores, patient attitudes towards adherence, and patch adhesiveness. 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). [ABSTRACT FROM AUTHOR]

Introduction We conducted an updated systematic review and meta-analysis of randomized controlled trials (RCTs) comparing blonanserin with other antipsychotics (amisulpride, aripiprazole, haloperidol, paliperidone, and risperidone). Methods Weighted mean difference (WMD), risk ratio, and number needed to harm (NNH) with 95% confidence intervals (95% CIs) were calculated using random-effects model. Results Ten RCTs (n = 1521) were included in this study. Blonanserin was superior to aripiprazole in improvement of Positive and Negative Syndrome Scale total scores (WMD = −10.62, 95% CI = −17.67 to −3.560, p = 0.003). Blonanserin was associated with a higher incidence of all-cause discontinuation (RR = 1.373, 95% CI = 1.088–1.734, p = 0.008, NNH = 11), akathisia, extrapyramidal disorder, and agitation/excitement and a lower risk of hyperprolactinemia compared with risperidone + paliperidone. Discussion The current meta-analytic study did not update the comparison of blonanserin vs. haloperidol because there were no new RCTs. Our results suggest that the efficacy of blonanserin for schizophrenia is comparable with that of other antipsychotics, and blonanserin seems to be well tolerated. [ABSTRACT FROM AUTHOR]

Background Blockade of D3 receptor, a member of the dopamine D2-like receptor family, has been suggested as a possible medication for schizophrenia. Blonanserin has high affinity in vitro for D3 as well as D2 receptors. We investigated whether a single dose of 12 mg blonanserin, which was within the daily clinical dose range (i.e., 8–24 mg) for the treatment of schizophrenia, occupies D3 as well as D2 receptors in healthy subjects. Methods Six healthy males (mean 35.7±7.6 years) received 2 positron emission tomography scans, the first prior to taking blonanserin, and the second 2 hours after the administration of a single dose of 12 mg blonanserin. Dopamine receptor occupancies by blonanserin were evaluated by [11C]-(+)-PHNO. Results Occupancy of each region by 12 mg blonanserin was: caudate (range 64.3%–81.5%; mean±SD, 74.3±5.6%), putamen (range 60.4%–84.3%; mean±SD, 73.3%±8.2%), ventral striatum (range 40.1%–88.2%; mean±SD, 60.8%±17.1%), globus pallidus (range 65.8%–87.6%; mean±SD, 75.7%±8.6%), and substantia nigra (range 56.0%–88.7%; mean±SD, 72.4%±11.0%). Correlation analysis between plasma concentration of blonanserin and receptor occupancy in D2-rich (caudate and putamen) and D3-rich (globus pallidus and substantia nigra) regions showed that EC50 for D2-rich region was 0.39 ng/mL (r=0.43) and EC50 for D3-rich region was 0.40 ng/mL (r=0.79). Conclusions A single dose of 12 mg blonanserin occupied D3 receptor to the same degree as D2 receptor in vivo. Our results were consistent with previous studies that reported that some of the pharmacological effect of blonanserin is mediated via D3 receptor antagonism. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the potential effects of a meal and grapefruit juice on the pharmacokinetics of blonanserin and its metabolite N-desethyl blonanserin in healthy Chinese volunteers. Methods: This was a single-centre, open-label, fixed-sequence study, where 12 healthy Chinese volunteers received a single dose of 8 mg blonanserin after an overnight fast in period 1 (reference), a high-fat meal during period 2 and with co-administration of 250 mL of grapefruit juice in period 3. The washout period was 7 days. Series of plasma samples were collected after each dose to determine concentrations of blonanserin and its metabolite N-desethyl blonanserin using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated by non-compartmental analysis and compared between periods by standard average bioequivalence ANOVA. Adverse events were monitored throughout the study. Results: All subjects completed the study. High-fat meals significantly increased blonanserin exposure (AUC) 2.58-fold (90% CI 2.21, 3.02), relative to the reference period. Co-administration of blonanserin with grapefruit juice remarkably prolonged elimination half-life of blonanserin (from 9.7 to 21.4 h) and significantly increased exposures to blonanserin and N-desethyl blonanserin by 5.82-fold (90% CI 4.57, 7.42) and 1.81-fold (90% CI 1.65, 1.98), respectively. Conclusions: These results suggested that blonanserin was largely metabolised in the intestinal tract before becoming systemically available, and both food and grapefruit juice enhanced exposure to blonanserin and N-desethyl blonanserin. Grapefruit juice increased bioavailability and may have reduced systemic clearance of blonanserin. Further intestinal CYP3A4 and hepatic CYP3A4 might be postulated to explain the delayed elimination of blonanserin. Dose adjustment of blonanserin is needed on the basis of co-intake of known strong CYP3A4 inhibitor. Patients taking high-dose blonanserin also need to be cautious about the ingestion of grapefruit juice. [ABSTRACT FROM AUTHOR]

Objective: There has been no direct comparison of aripiprazole and blonanserin for schizophrenia treatment. We conducted a 24-week, rater-masked, randomized trial of aripiprazole (6-30 mg/d) vs blonanserin (4-24 mg/d) in schizophrenia patients who were not taking any antipsychotic medication for more than 2 weeks before enrollment (UMIN000011194). Methods: The primary outcome measure for efficacy was improvement of Positive and Negative Syndrome Scale (PANSS) total score at week 24. Secondary outcomes were PANSS subscale scores, 21-item Hamilton Rating Scale for Depression (HAMD-21) score, response rate, discontinuation rate, and individual adverse events. Results: Forty-four patients were recruited. The discontinuation rate was 86.4% in the aripiprazole group and 68.2% in the blonanserin treatment group. There was no significant difference in mean time to discontinuation between the groups. Although both treatment groups showed significant reductions in the PANSS total score, PANSS subscale scores, and HAMD-21 scores at week 24, the magnitudes of the changes did not differ between the groups. There were no significant differences in the incidences of adverse events including somnolence, extrapyramidal symptoms, prolactin-related adverse events, and weight change between the groups. Conclusion: Our results suggest similar efficacy and safety profiles of aripiprazole and blonanserin in the patients with schizophrenia. Double-blind controlled studies are needed to further explore the efficacy and safety of aripiprazole and blonanserin in schizophrenia. [ABSTRACT FROM AUTHOR]