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

Purpose: This study aims to comprehensively assess the safety of Asenapine by conducting an comprehensive statistical analysis of adverse event reports in the FAERS database, with a particular focus on potential adverse reactions related to its use in the treatment of psychiatric disorders. Methods: Event reports from the first quarter of 2009 to the third quarter of 2023 were collected and analyzed. Detailed examinations of gender, age, reporter identity, and other aspects were conducted to reveal the fundamental characteristics of Asenapine-related adverse events. Signal mining techniques were employed to systematically evaluate various adverse reactions associated with Asenapine. Results: The study found that adverse event reports involving Asenapine were more common among female patients, with the age group mainly distributed between 18 and 45 years. Physicians were the primary reporters of adverse events, and psychiatric disorders, neurological disorders, and gastrointestinal disorders were the most common areas affected by adverse reactions. In addition to known adverse reactions, potential risks not mentioned in the drug label were identified, such as anosognosia, attentional drift, and psychogenic compensation disorder. Conclusion: Asenapine carries the risk of various adverse reactions alongside its therapeutic effects. In clinical practice, physicians should closely monitor the occurrence of neurological disorders, psychiatric disorders, and gastrointestinal system disorders. [ABSTRACT FROM AUTHOR]

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

Leslie Citrome,1 Mariacristina Castelli,2 Masami Hasebe,3 Takaaki Terahara,3 Justin Faden,4 Marina Komaroff2 1Department of Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, NY, USA; 2Product Development, Noven Pharmaceuticals, Inc, Jersey City, NJ, USA; 3Hisamitsu Pharmaceutical Co., Inc, Tokyo, Japan; 4Department of Psychiatry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USACorrespondence: Leslie Citrome, Department of Psychiatry and Behavioral Sciences, New York Medical College, 40 Sunshine Cottage Road, Valhalla, NY, 10595, USA, Tel +1 845-362-2081, Email nntman@gmail.comIntroduction: HP-3070, a once-daily asenapine transdermal system, is the first antipsychotic “patch” formulation FDA approved for adults with schizophrenia. Positive and Negative Syndrome Scale (PANSS) score items can be grouped into a five-factor structure to describe specific schizophrenia symptom domains. This post hoc analysis of data from a pivotal study evaluated HP-3070’s efficacy by examining these factors.Methods: In a phase 3 study, adults with an acute exacerbation of schizophrenia were randomized to six weeks of treatment with HP-3070 3.8mg/24h, 7.6mg/24h, or placebo. An analysis was performed using the five PANSS factor domains (negative symptoms, positive symptoms, disorganized thought, uncontrolled hostility/excitement, anxiety/depression). Mixed-model repeated-measures (MMRM) analysis included change from baseline (CFB) in PANSS factor score as the repeated dependent variable, with country, treatment, visit, treatment by visit interaction, and baseline PANSS score as covariates.Results: The analysis included 607 patients. Treatment with HP-3070 3.8mg/24h resulted in a statistically significant LS mean CFB (improvement) vs placebo at Weeks 4– 6 for all domains except for anxiety/depression, where a numerical difference was observed in favor of active treatments. Among the domains, the positive symptom factor demonstrated the numerically greatest LS mean (SE) difference from placebo in CFB, which for HP-3070 7.6mg/24h was − 2.0 [0.57] and for HP-3070 3.8mg/24h was − 2.3 [0.57]; P< 0.001 for both. Treatment effect size for the positive symptom factor using Cohen’s d (95% confidence intervals) was 0.39 (0.17, 0.61) for HP-3070 7.6mg/24h and 0.45 (0.20, 0.64) for HP-3070 3.8mg/24h.Discussion: Post hoc analysis using a PANSS five-factor model suggests that HP-3070 may address a broad range of symptoms in people with schizophrenia.Keywords: asenapine, transdermal, patch, schizophrenia, positive and negative syndrome scale, five-factor

Abstract Aim Patients with cancer often experience nausea and vomiting (N/V), but may have difficulty using olanzapine (OLZ), a common antiemetic. Asenapine (ASE) is a multi‐acting receptor‐targeted antipsychotic like OLZ, although there is little evidence that ASE serves as an antiemetic. The aim of this study was to evaluate the efficacy and tolerability of ASE compared to those of OLZ for the treatment of N/V in patients with cancer. Methods This retrospective study involved patients who received 5 mg ASE, 5 mg OLZ, or 2.5 mg OLZ for 2 days. Daily worst N/V was rated on a scale of 0 (none) to 3 (very much). The primary endpoint was the proportion of patients who had a response, defined as any reduction in N/V score. A complete response (CR) was defined as a score reduction to 0. Secondary endpoints included the proportion of patients with CR and adverse events. Results Between April 2017 and March 2023, 212 patients were enrolled to receive treatment: 5 mg ASE (n = 34), 5 mg OLZ (n = 102), or 2.5 mg OLZ (n = 76). No significant differences in response rates (52.9% vs. 58.8% vs. 52.6%, p = 0.671) or secondary endpoints were observed between the groups. Patients receiving ASE were more likely to experience oral hypoesthesia (p = 0.004). Conclusion This preliminary study suggests that ASE may be effective for N/V. Further studies are required to confirm these findings.

Abstract Aims A meta‐analysis of short‐term studies revealed no significant differences between the doses of asenapine, 10 and 20 mg/day, in the acute treatment of schizophrenia. However, it should be noted that many patients from clinical practice were excluded, and the dose–response to asenapine in a real‐world setting is still unclear. Additionally, the dose–response in the maintenance phase is not clear. This study aimed to evaluate the differences in the efficacy of different asenapine doses in patients with maintenance phase of schizophrenia in a real‐world setting. Methods This study conducted post‐marketing surveillance of asenapine in clinical settings in Japan. It followed patients diagnosed with schizophrenia who received asenapine for the first time for a maximum of 52 weeks. These patients were divided into two categories based on their average daily asenapine dosage: ≤10 mg/day and >10 mg/day. Asenapine efficacy was assessed by adjusting for patient demographics using multivariate logistic regression analysis, employing the Clinical Global Impression‐Global Improvement (CGI‐I) scale, which has seven categories. Results A total of 2774 patients were included in the analysis. Of these, 1689 and 1085 patients were treated with asenapine ≤10 mg/day and >10 mg/day, respectively. The CGI‐I improvement rate was significantly higher in the asenapine >10 group (p = 0.012) after adjusting for patient background factors. Conclusion These results suggest that asenapine doses >10 mg/day may be more effective than 10 mg/day in the treatment of schizophrenia; however, further studies are needed to confirm these findings.

Abstract Background Asenapine has unique orally-related side effects, such as a bitter taste induced by sublingual administration, which often results in discontinuation of the medication. While the FDA has approved black-cherry-flavored asenapine, several countries have prescribed only unflavored versions. Specifically, Asians commonly report experiencing the bitterness of asenapine because they are more sensitive to bitter tastes than other ethnic groups. In this study, with the aim of improving adherence by reducing the bitterness of asenapine, we investigated the effects of d-sorbitol, which reduced the bitterness parameters of taste sensors in our previous basic study on the bitterness and continuity of asenapine among patients with schizophrenia. Methods Twenty adult patients with schizophrenia were included in this single-blind, placebo-controlled, crossover trial. Participants rinsed their mouths with single-administration of d-sorbitol or a placebo prior to each administration of asenapine. We then conducted the questionnaires and assessed changes in the bitterness of asenapine (primary end point) and willingness to continue its use (secondary end point). Results d-sorbitol significantly improved the bitterness of asenapine (p = 0.038). Although it did not significantly increase the willingness to continue asenapine (p = 0.180), it did show improvement over the placebo in enhancing willingness to continue, especially in patients who were not accustomed to its taste. Conclusion Our findings indicate that single-administration of d-sorbitol significantly reduces the bitterness of asenapine. In countries where flavored asenapine is not available, this finding could benefit patients who were not accustomed to its bitter taste. Trial registration This study was registered in the Japan Registry of Clinical Trials (jRCTs041210019) on May 14, 2021.

Aim: Patients with cancer often experience nausea and vomiting (N/V), but may have difficulty using olanzapine (OLZ), a common antiemetic. Asenapine (ASE) is a multi‐acting receptor‐targeted antipsychotic like OLZ, although there is little evidence that ASE serves as an antiemetic. The aim of this study was to evaluate the efficacy and tolerability of ASE compared to those of OLZ for the treatment of N/V in patients with cancer. Methods: This retrospective study involved patients who received 5 mg ASE, 5 mg OLZ, or 2.5 mg OLZ for 2 days. Daily worst N/V was rated on a scale of 0 (none) to 3 (very much). The primary endpoint was the proportion of patients who had a response, defined as any reduction in N/V score. A complete response (CR) was defined as a score reduction to 0. Secondary endpoints included the proportion of patients with CR and adverse events. Results: Between April 2017 and March 2023, 212 patients were enrolled to receive treatment: 5 mg ASE (n = 34), 5 mg OLZ (n = 102), or 2.5 mg OLZ (n = 76). No significant differences in response rates (52.9% vs. 58.8% vs. 52.6%, p = 0.671) or secondary endpoints were observed between the groups. Patients receiving ASE were more likely to experience oral hypoesthesia (p = 0.004). Conclusion: This preliminary study suggests that ASE may be effective for N/V. Further studies are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Aims: A meta‐analysis of short‐term studies revealed no significant differences between the doses of asenapine, 10 and 20 mg/day, in the acute treatment of schizophrenia. However, it should be noted that many patients from clinical practice were excluded, and the dose–response to asenapine in a real‐world setting is still unclear. Additionally, the dose–response in the maintenance phase is not clear. This study aimed to evaluate the differences in the efficacy of different asenapine doses in patients with maintenance phase of schizophrenia in a real‐world setting. Methods: This study conducted post‐marketing surveillance of asenapine in clinical settings in Japan. It followed patients diagnosed with schizophrenia who received asenapine for the first time for a maximum of 52 weeks. These patients were divided into two categories based on their average daily asenapine dosage: ≤10 mg/day and >10 mg/day. Asenapine efficacy was assessed by adjusting for patient demographics using multivariate logistic regression analysis, employing the Clinical Global Impression‐Global Improvement (CGI‐I) scale, which has seven categories. Results: A total of 2774 patients were included in the analysis. Of these, 1689 and 1085 patients were treated with asenapine ≤10 mg/day and >10 mg/day, respectively. The CGI‐I improvement rate was significantly higher in the asenapine >10 group (p = 0.012) after adjusting for patient background factors. Conclusion: These results suggest that asenapine doses >10 mg/day may be more effective than 10 mg/day in the treatment of schizophrenia; however, further studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Abstract After completion of a 6‐week double‐blind trial of asenapine sublingual tablets (10 or 20 mg/day) versus placebo in Asian patients with acute exacerbation of schizophrenia, including Japanese patients, this open‐label study evaluated the safety and efficacy of a 52‐week treatment with asenapine at flexible doses. In 201 subjects, including 44 who had received placebo (P/A group) and 157 who had received asenapine (A/A group) in the feeder trial, adverse events occurred at rates of 90.9% and 85.4% and serious adverse events at rates of 11.4% and 20.4%, respectively. One patient in the P/A group died. No clinically significant abnormal measurements of body weight, body mass index, or glycated hemoglobin, fasting plasma glucose, insulin, and prolactin levels were observed. The sustained efficacy rate, as evaluated by the Positive and Negative Syndrome Scale total score and other measures, remained at approximately 50% between 6 and 12 months of treatment. These results suggest that long‐term treatment with asenapine is well tolerated and provides sustained efficacy.

After completion of a 6‐week double‐blind trial of asenapine sublingual tablets (10 or 20 mg/day) versus placebo in Asian patients with acute exacerbation of schizophrenia, including Japanese patients, this open‐label study evaluated the safety and efficacy of a 52‐week treatment with asenapine at flexible doses. In 201 subjects, including 44 who had received placebo (P/A group) and 157 who had received asenapine (A/A group) in the feeder trial, adverse events occurred at rates of 90.9% and 85.4% and serious adverse events at rates of 11.4% and 20.4%, respectively. One patient in the P/A group died. No clinically significant abnormal measurements of body weight, body mass index, or glycated hemoglobin, fasting plasma glucose, insulin, and prolactin levels were observed. The sustained efficacy rate, as evaluated by the Positive and Negative Syndrome Scale total score and other measures, remained at approximately 50% between 6 and 12 months of treatment. These results suggest that long‐term treatment with asenapine is well tolerated and provides sustained efficacy. [ABSTRACT FROM AUTHOR]

The objective of our study, which combined API-ILs strategy and controlled-release polymers, was to prepare a 72 h long-acting drug-in-adhesive patch for optimum delivery of asenapine (ASE). Special attention was paid to the permeation promotion mechanism and the controlled release behavior of ASE-ILs in pressure sensitive adhesives (PSA). Formulation factors were investigated by ex vivo transdermal experiments. The optimized patch was evaluated by pharmacokinetics study and skin irritation test. The obtained formulation was as follows, 15% w/w ASE-MA (about 1136 μg/cm2 ASE, 413 μg/cm2 MA), AACONH 2 (Amide adhesive) as the matrix, 80 μm thickness, backing film of CoTran™ 9733. The optimized patch displayed satisfactory ex vivo and in vivo performance with Q 72 h of 620 ± 44 µg/cm2 and F abs of 62.4%, which utilization rate (54.6%) was significantly higher than the control group (38.3%). By using the classical shake flask method, 13C NMR, DSC, and FTIR, the physicochemical properties and structure of ILs were characterized. log D o/w , ATR-FTIR, Raman, and molecular dynamics simulation results confirmed that ASE-MA (MA: 3-Methoxypropionic acid) had appropriate lipophilicity, and affected lipid fluidity as well as the conformation of keratin to improve the skin permeation. The FTIR, MDSC, rheology, and molecular docking results revealed that hydrogen bond (H-bond), were formed between ASE-MA and PSA, and the drug increased the molecular mobility of polymer chains. In summary, the 72 h long-acting patch of ASE was successfully prepared and it supplied a reference for the design of long-acting patches with ASE. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Background Antipsychotics are essential in the acute treatment of and maintenance therapy for schizophrenia, but medication adherence and long-term treatment continuity are needed to maximize their effectiveness. Each antipsychotic has various side effects, which may affect adherence. Some patients with schizophrenia are reluctant to take asenapine because of its unique oral-related side effects, such as the bitter taste caused by sublingual administration. Our previous basic research found that D-sorbitol lowered the bitterness parameters of the taste sensors. However, whether D-sorbitol has the same effect in patients remains unclear. Therefore, using a D-sorbitol solution, we aim to evaluate changes in the bitterness of asenapine among patients with schizophrenia. Methods In this single-blind, placebo-controlled, crossover trial, we plan to recruit 20 adult patients with schizophrenia spectrum disorder who take sublingual asenapine tablets. The participants will be divided into two groups (n = 10 each). Each group will be given a D-sorbitol or placebo solution on the first day for rinsing before taking the sublingual asenapine tablets. After a 1-day interval, the participants will rinse their mouths again with a different liquid. Questionnaires regarding changes in taste and the willingness to continue asenapine will be conducted before the start of the study and after each rinse. The primary and secondary end points will be a taste evaluation of bitterness, and the willingness to continue asenapine, respectively. Differences in questionnaire scores between the D-sorbitol and placebo solutions will be calculated and analyzed using a McNemar test. Discussion This study aims to determine the efficacy of D-sorbitol in masking the bitter taste of asenapine. To our knowledge, it is the first intervention study using D-sorbitol for bitter taste of asenapine in patients with schizophrenia. Evidence of the efficacy of D-sorbitol could result in D-sorbitol pretreatment being an easy and inexpensive means of improving adherence to asenapine. Trial registration This study was registered in the Japan Registry of Clinical Trials jRCTs041210019, on May 14, 2021. Ethics approval was obtained from the Nagoya University Clinical Research Review Board.