Safety and effectiveness of oral medium to high dose blonanserin in patients with schizophrenia: subgroup analysis from a prospective, multicenter, post-marketing surveillance study in mainland China
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SUBMITTER: Yang Y
PROVIDER: S-EPMC10557194 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:Background/purposeBlonanserin is an atypical antipsychotic, a potent selective antagonist of dopamine D2 receptor (D2), prescribed as oral formulations in patients with schizophrenia. Blonanserin transdermal patch was developed to provide a new treatment option, but the corresponding dose to oral blonanserin was not clear. The aims of this study were to clarify the pharmacokinetic (PK)-pharmacodynamic characteristics of blonanserin after transdermal patch application and to evaluate the corresponding dose to oral formulation based on striatal D2 occupancy.MethodsThe relationship between D2 occupancy and plasma blonanserin concentration was analyzed using an Emax model based on data from positron emission tomography study with oral and transdermal blonanserin. D2 occupancy was simulated using Emax models based on the observed plasma concentrations and the simulated plasma concentrations obtained from population PK model.ResultsPlasma blonanserin concentration levels after repeated patch applications were nearly stable throughout the day and no effect of sex, advanced age, or application site was detected. The concentration at half maximal D2 occupancy during transdermal patch applications, 0.857 ng/mL, was higher than that after oral doses, 0.112 ng/mL, suggesting metabolite contribution after oral doses. The median predicted D2 occupancy during blonanserin patch applications at doses of 40 and 80 mg/d was 48.7% and 62.5%, respectively, and the distribution of D2 occupancy at these doses could cover most of that at oral doses of 8 to 24 mg/d.ConclusionsPredicted D2 occupancy suggested that a 40- to 80-mg/d blonanserin transdermal patch dose corresponds to an 8- to 24-mg/d oral dose for the treatment of schizophrenia.
| S-EPMC9042341 | biostudies-literature
Project description: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.
| S-EPMC9435526 | biostudies-literature
Project description:BackgroundLaxative use has recently been indicated as a risk factor for hospitalization in patients with schizophrenia. Oral antipsychotic therapy for patients with schizophrenia treated with laxatives may be problematic due to gastrointestinal dysfunction, which affects absorption. Therefore, transdermal patches of antipsychotics may be a suitable alternative. We herein compared the efficacies of a blonanserin (BNS) patch and BNS oral formulation in patients with schizophrenia treated with laxatives.MethodsA retrospective cohort study was performed using a claims database in Japan provided by DeSC Healthcare Inc. Subjects were BNS patch- or BNS oral formulation-prescribed patients with schizophrenia. The primary outcome was hospitalization to psychiatric wards. The hazard ratio (HR) for hospitalization was estimated using Cox proportional hazards model and adjusted by propensity scores.ResultsAmong the 3896 patients identified, 1407 were prescribed laxatives (BNS patch group: n = 538, BNS oral group: n = 869). Mean ages in the BNS patch and BNS oral groups were 74 and 58 years, respectively. The adjusted HR for hospitalization (BNS patch group vs. BNS oral group) was 1.31 (95% confidence interval; 0.88, 1.94), with no significant difference.ConclusionsNo significant difference was observed in the risk of hospitalization for patients with schizophrenia treated with laxatives between the BNS patch and BNS oral groups. The effectiveness of antipsychotic patches in these patients warrants further research that considers factors such as patch preference in the elderly.
| S-EPMC11843157 | biostudies-literature
Project description:BackgroundIn Japan, anagrelide has been approved for use in patients with essential thrombocythemia. Here, the safety and efficacy of anagrelide was assessed in clinical practice as post-marketing surveillance. Subgroup analyses were conducted to compare patients (1) with or without a history of cytoreductive therapy (CRT), (2) <60 or ≥60 years of age, and (3) with an anagrelide starting dose of ≤0.5 mg/day or 1.0 mg/day.MethodsData were collected for all patients who received anagrelide, with an observation period of 12 months after treatment initiation.ResultsOf the 648 patients, 54.3% experienced adverse drug reactions (ADRs). The most commonly reported ADRs were headaches, palpitations, and anemia. No significant difference was observed in overall ADRs across patient subgroups. A significantly higher incidence of headaches was observed in patients < 60 years versus those ≥ 60 years (P < 0.001). The incidence of anemia and serious ADRs were significantly higher in patients ≥ 60 years, and those with a history of CRT (P < 0.05). The discontinuation rate at 6 months was significantly lower in patients started at the lower anagrelide dose (P < 0.05). Platelet counts decreased in all analyzed groups.ConclusionsThis surveillance showed that anagrelide has a tolerable safety and efficacy profile.
| S-EPMC9515010 | biostudies-literature
Project description:ObjectiveThis 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.MethodsA 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).ResultsBlonanserin 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.ConclusionsBlonanserin 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.
| S-EPMC7292269 | biostudies-literature
Project description:BackgroundBlonanserin is a second-generation antipsychotic used for the treatment of schizophrenia in Japan and Korea. The present study aimed to examine early prediction of blonanserin in patients with schizophrenia.MethodsAn 8-week, prospective, single-arm, flexible-dose clinical trial of blonanserin in patients with schizophrenia was conducted under real-world conditions. The inclusion criteria were antipsychotic naïve, and first-episode schizophrenia patients or schizophrenia patients with no consumption of any antipsychotic medication for more than 4 weeks before enrollment in this study. The positive predictive value, negative predictive value, sensitivity, specificity, and predictive power were calculated for the response status at week 4 to predict the subsequent response at week 8.ResultsThirty-seven patients were recruited (56.8% of them had first-episode schizophrenia), and 28 (75.7%) completed the trial. At week 8, blonanserin was associated with a significant improvement in the Positive and Negative Syndrome Scale (PANSS) total score (P<0.0001) and in positive (P<0.0001), negative (P<0.0001), and general subscale scores (P<0.0001). In terms of percentage improvement of PANSS total scores from baseline to week 8, 64.9% of patients showed a ≥20% reduction in the PANSS total score and 48.6% showed a ≥30% reduction. However, 8.1% of patients experienced at least one adverse event. Using the 20% reduction in the PANSS total score at week 4 as a definition of an early response, the negative predictive values for later responses (ie, reductions of ≥30 and ≥40 in the PANSS total scores) were 88.9% and 94.1%, respectively. The specificities were 80.0% and 51.6%, respectively.ConclusionOur results suggest that the blonanserin response at week 4 could predict the later response at week 8.
| S-EPMC4181750 | biostudies-literature
Project description: Not available
| S-EPMC6982629 | biostudies-literature
Project description:ObjectiveTo 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.MethodsOf 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.ConclusionsBlonanserin 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.
| S-EPMC7292214 | biostudies-literature
Project description:Background: Pirfenidone, an antifibrotic medication approved for the treatment of idiopathic pulmonary fibrosis (IPF), often requires dose reduction owing to adverse events. In this study, we evaluated if pirfenidone's reduced dose has any impact on clinical outcomes in patients with IPF. Methods: We used the data of a prospective post-marketing study of pirfenidone conducted at 10 hospitals in South Korea from 2014 to 2017. Dose reduction was defined when the pirfenidone dose was temporarily or permanently reduced to manage adverse events or when the treatment dose failed to reach the standard dose. Study patients were classified based on the most frequently administered dose during 48-week follow-up-1800 mg, 1,200 mg, and <1,200 mg/days. The following clinical outcomes were compared between the groups: death, hospitalization, acute exacerbation, pulmonary function decline, and changes in severity of dyspnea and cough. Results: The median follow-up duration in all 143 patients was 11 months. During the study period, 70.6% experienced at least one dose reduction. Patients treated with standard-dose pirfenidone tended to be young and had the lowest diffusing capacity. Pulmonary function changes did not differ depending on the pirfenidone dose. The three groups were not significantly different in terms of the proportion of death, hospitalization, and acute exacerbation. The symptom changes were also similar between the groups. Conclusion: Reduced doses did not negatively impact clinical outcomes compared with the standard-dose pirfenidone in patients with IPF. Dose reduction may be a useful method to manage adverse events while maintaining therapeutic efficacy.
| S-EPMC9871582 | biostudies-literature
Project description:AimTo explore the optimal dose of blonanserin transdermal patch (BNS-P) based on baseline psychiatric symptomatic characteristics during acute schizophrenia.MethodsA post hoc cluster analysis was conducted using data from a 6-week randomized, double-blind, placebo-controlled study of BNS-P (40 or 80 mg/day) in acute schizophrenia. We classified patients into three clusters based on baseline psychiatric symptoms. Efficacy was assessed using the change from baseline to week 6 in the PANSS total score. Safety was assessed by the incidence of adverse events.ResultsAmong 577 patients, three clusters were identified, characterized by severe psychiatric (Cluster-S; n = 122), predominant negative (Cluster-N; n = 191), and predominant positive (Cluster-P; n = 264) symptoms. In Cluster-P, both BNS-P 40 and 80 mg/day reduced PANSS total score significantly more than placebo (p = 0.036, effect size = 0.342; p < 0.001, effect size = 0.687, respectively). In Cluster-S and -N, only BNS-P 80 mg/day reduced PANSS total score significantly more than placebo (p = 0.045, effect size = 0.497; p = 0.034, effect size = 0.393, respectively). The effect size was greater at 80 mg/day than at 40 mg/day across all clusters. The most common treatment-emergent adverse events were akathisia and skin-related adverse events in all clusters.ConclusionBNS-P exhibited a dose-dependent antipsychotic effect in all clusters, particularly highlighting its efficacy in patients with predominant positive symptoms, even at lower doses. These findings provide novel and valuable insights for determining BNS-P dose tailoring to individual symptomatic characteristics in real-world practice.
| S-EPMC11609747 | biostudies-literature