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AbstractObjectiveMethodsResultsConclusion\nPLAIN LANGUAGE SUMMARYPatients with schizophrenia value improved life engagement, a term that describes positive health aspects across emotional, physical, social, and cognitive domains. This post hoc analysis of clinical trial data aimed to investigate the effect of brexpiprazole on patient life engagement in schizophrenia over the short and long term.Data were pooled from three 6-week, randomized, double-blind, placebo-controlled clinical trials (ClinicalTrials.gov identifiers: NCT01396421, NCT01393613, NCT01810380; N = 1385) and two 52-week, open-label extension studies (NCT01397786, NCT01810783; N = 408) of brexpiprazole in adults with schizophrenia. Patient life engagement was measured using a subset of 14 Positive and Negative Syndrome Scale items (score range: 14 [best] to 98 [worst]) that has previously demonstrated content validity. Mean score changes and response rates (based on minimal clinically important difference estimates of ≥5 and ≥10 points) were calculated.Greater improvement in patient life engagement from baseline to Week 6 was observed for brexpiprazole 2–4 mg/day (least squares mean [standard error] change: −8.3 [0.3]; n = 868) versus placebo (−5.7 [0.4]; n = 517), with a least squares mean difference of −2.58 (95% confidence interval: −3.57 to −1.58; p < 0.001; Cohen’s d effect size: 0.28). These improvements were maintained over 58 weeks on brexpiprazole 1–4 mg/day (n = 399). At Week 6, response rates among patients treated with brexpiprazole versus placebo were 71.6% versus 58.0% (≥5-point improvement; p < 0.001) and 43.5% versus 32.8% (≥10-point improvement; p < 0.001). At Week 58 (n = 179), response rates among patients treated with brexpiprazole were 90.5% (≥5-point improvement) and 78.2% (≥10-point improvement).Beyond its efficacy on psychotic symptoms, brexpiprazole has the potential to improve patient life engagement – an important patient-centered outcome in schizophrenia.Schizophrenia is a serious mental disorder in which people may hear, see, or believe things that do not exist. Most people with schizophrenia hope to become more engaged with life, as well as to improve their schizophrenia symptoms. Being engaged with life means feeling happy and hopeful, having energy and motivation, being interested and involved in activities, and being alert and thinking clearly. This study investigated if brexpiprazole, a medicine for schizophrenia and some other medical conditions, can help to improve patients’ engagement with life. The researchers looked at data from over a thousand people with schizophrenia across five previously completed clinical trials. To measure ‘patient life engagement’, the researchers used data from a questionnaire filled in by doctors during their meetings with the patients. The results showed that, on average, people taking brexpiprazole (rather than a ‘placebo’ tablet) became more engaged with life over the first 6 weeks of treatment. For some people who kept taking brexpiprazole, these improvements lasted for over a year. This means that brexpiprazole may help people with schizophrenia to become more engaged with life, as well as improving their schizophrenia symptoms. [ABSTRACT FROM AUTHOR]

Introduction: Agitation is a common and disruptive syndrome in dementia due to Alzheimer's disease (AD). Brexpiprazole was recently approved for this agitation of AD dementia and is the only therapy approved for this indication. Areas covered: The authors review the chemistry, pharmacokinetics, mechanism of action, and pharmacodynamics of brexpiprazole. Phase 2/3 and Phase 3 studies of brexpiprazole for the treatment of agitation in dementia due to AD are described. These studies demonstrated efficacy and safety for the 2 mg/d and 3 mg/d doses. Agitation reduction from baseline was significantly greater in the active treatment groups compared to the participants on placebo as measured by the Cohen-Mansfield Agitation Inventory, the primary outcome. Treatment benefit was demonstrated on the Clinician Global Impression – Severity, the key secondary outcome. Safety and tolerability were comparable in drug and placebo arms of the studies. Expert opinion: Approval by the Food and Drug Administration (FDA) of brexpiprazole for the treatment of agitation in dementia due to AD is an important milestone and regulatory precedent. This is the first approval for the treatment of any neuropsychiatric syndrome of AD. Brexpiprazole has a 'black box' warning for its use in psychosis caused by dementia due to an observed increase in mortality when using this class of antipsychotic agents in patients with dementia. Post-marketing surveillance will be key to understanding the safety profile of brexpiprazole. Brexpiprazole may be prioritized over the 'off label' use of other potential treatments for agitation. [ABSTRACT FROM AUTHOR]

Background: A 12-week randomized controlled trial demonstrated that brexpiprazole is efficacious for treating agitation in patients with dementia due to Alzheimer's disease. Objective: To assess the long-term safety and tolerability of brexpiprazole for the treatment of agitation associated with dementia due to Alzheimer's disease. Methods: This 12-week, active-treatment (oral brexpiprazole 2 or 3 mg/day) extension trial ran from October 2018–September 2022 at 66 sites in Europe/US. Patients with agitation in dementia due to Alzheimer's disease in a care facility/community-based setting who completed the randomized trial were eligible (N = 259 enrolled/analyzed for safety; 88.4% completed). Stable Alzheimer's disease medications were permitted. The primary safety endpoint was the frequency and severity of treatment-emergent adverse events (TEAEs). Change in Cohen-Mansfield Agitation Inventory (CMAI) total score was an exploratory efficacy endpoint. Results: Mean (SD) age was 74.3 (7.6) years, 145 patients (56.0%) were female, and 248 (95.8%) were White. TEAEs were reported by 67 patients (25.9%), most commonly headache (3.5%) and fall (2.3%). Most TEAEs were mild or moderate in severity; 5 patients (1.9%) reported a severe TEAE, including 3 severe falls attributed to tripping, misjudging sitting, or dehydration. Twelve patients (4.6%) discontinued due to TEAEs. No patients died. Mean CMAI total score improved by 9.1 points over 12 weeks. Conclusions: Considering the randomized and extension trials together, brexpiprazole 2 or 3 mg was generally well tolerated for up to 24 weeks in elderly patients with agitation associated with dementia due to Alzheimer's disease. Patients showed continued improvement in agitation. ClinicalTrials.gov identifier: NCT03594123 (registration date: July 11, 2018). [ABSTRACT FROM AUTHOR]

INTRODUCTION: We evaluated the efficacy and safety of brexpiprazole for the treatment of agitation in Alzheimer's dementia (AAD) in Japanese patients. METHODS: This was a phase 2/3 multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group study. Patients with AAD were randomized to receive brexpiprazole 1 mg/day or 2 mg/day, or placebo (3:4:4) for 10 weeks. RESULTS: For the primary endpoint (change in Cohen‐Mansfield Agitation Inventory [CMAI] total score from baseline to Week 10), both brexpiprazole 1 mg and 2 mg groups demonstrated statistically significant improvement versus placebo (2 mg: least squares [LS] mean difference –7.2 [95% confidence interval (CI): –10.0 to –4.3], p‐value < 0.0001, 1 mg: LS mean difference –3.7 [95% CI: –6.8 to –0.7], p‐value = 0.0175). The incidences of treatment‐emergent adverse events reported in the brexpiprazole 1 mg, 2 mg, and placebo groups were 76.8%, 84.6%, and 73.8%, respectively. DISCUSSION: Brexpiprazole 1 mg/day and 2 mg/day for 10 weeks was efficacious and well tolerated. Highlights: Brexpiprazole treatment for 10 weeks improved agitation in Alzheimer's dementia.The efficacy of brexpiprazole 1 mg/day has been confirmed for the first time.The incidence of adverse events was higher compared to the previous studies.Both brexpiprazole 1 mg/day and 2 mg/day were generally well tolerated. [ABSTRACT FROM AUTHOR]

Abstract Aim Brexpiprazole is the first FDA‐approved treatment for agitation associated with dementia due to Alzheimer's disease. Agitation in Alzheimer's dementia (AAD) occurs in high prevalence and is a great burden for patients and caregivers. Efficacy, safety, and tolerability of brexpiprazole were demonstrated in the AAD clinical trials. To demonstrate the agitation‐ameliorating effect of brexpiprazole in animals, we evaluated brexpiprazole in two AAD mouse models. Methods The resident–intruder test was conducted in 5‐ to 6‐month‐old Tg2576 mice, given vehicle or brexpiprazole (0.01 or 0.03 mg/kg) orally 1 h before the test. Locomotor activity was measured in 6‐month‐old APPSL‐Tg mice given vehicle or brexpiprazole (0.01 or 0.03 mg/kg) orally the evening before the start of locomotor measurement for 3 days. Results In the resident–intruder test, Tg2576 mice showed significantly higher attack number and shorter latency to first attack compared to non‐Tg mice. In the Tg mice, brexpiprazole treatment (0.03 mg/kg) significantly delayed the latency to first attack and showed a trend toward a decrease in attack number. APPSL‐Tg mice (≧6 months old) showed significantly higher locomotion during dark period Phase II (Zeitgeber time [ZT] 16–20) and Phase III (ZT20‐24) compared to non‐Tg mice, correlating with the clinical observations of late afternoon agitation in Alzheimer's disease. Brexpiprazole treatment (0.01 and 0.03 mg/kg) significantly decreased hyperlocomotion during the Phase III in APPSL‐Tg mice. Conclusion The suppression of attack behavior and the reduction of nocturnal hyperlocomotion in these Tg mice may be indicative of the therapeutic effect of brexpiprazole on AAD, as demonstrated in the clinical trials.

Antipsychotics such as phenothiazines, pimozide, flupentixol and brexpiprazole have been shown to have good antitumor effects. Brexpiprazole, the successor to aripiprazole, has a better safety profile. Brexpiprazole promotes the death of tumor cells by inhibiting the proliferation of tumor stem cells, resolving the resistance of tumor cells to EGFR-TKIs, and promoting the sensitivity of tumor cells to chemotherapeutic agents, thus inhibiting the development of colorectal, lung, glioblastoma, pancreatic, and gastric cancers. This review focuses on the antitumor effects of antipsychotic drugs, especially the inhibitory effect of brexpiprazole on tumor cells, aiming to provide a theoretical basis for antipsychotic drugs in antitumor field. [ABSTRACT FROM AUTHOR]

In order to accelerate drug development and avoid unnecessary drug trials in vulnerable pediatric populations, the US Food and Drug Administration (FDA) released a general advice letter to sponsors permitting the effectiveness of atypical antipsychotics for the treatment of schizophrenia in adults to be extrapolated to adolescents. Extrapolation is based on the evidence‐based assumptions that (1) disease characteristics and (2) response to therapy, are similar in adults and adolescents. Whereas the FDA validated the extrapolation approach using data from multiple drug development programs, aripiprazole data are the most relevant to confirm the validity of the extrapolation approach for brexpiprazole, since aripiprazole and brexpiprazole both modulate dopaminergic and serotonergic signaling in the brain. The aims of this analysis were (1) to quantitatively assess the aripiprazole exposure (average steady‐state concentration)–response (Positive and Negative Syndrome Scale total score change from baseline) similarity between adults and adolescents with schizophrenia, (2) to extend the aripiprazole exposure–response modeling to brexpiprazole using adult data, and (3) to use the brexpiprazole model to predict schizophrenia symptom response in adolescents. Disease–drug–dropout models were developed using patient‐level data from clinical studies of aripiprazole (1007 adults, 294 adolescents) and brexpiprazole (1235 adults) in schizophrenia. The aripiprazole model demonstrated similar exposure–response between adults and adolescents with schizophrenia, validating the extrapolation approach. Extrapolation of the brexpiprazole adult exposure–response model to adolescents predicted the efficacy of brexpiprazole in adolescents aged 13‐17 years with schizophrenia. [ABSTRACT FROM AUTHOR]

Recent randomized controlled trials (RCTs) have shown a benefit of brexpiprazole in managing agitation in patients with Alzheimer's disease (AD). However, its efficacy and safety remain unclear. We systematically searched PubMed, Embase, and Cochrane Library for RCTs comparing brexpiprazole with placebo in patients with agitation and AD. Three studies comprising 1,048 patients were included. In patients with agitation and AD, brexpiprazole significantly improved the Cohen-Mansfield Agitation Inventory total score (CMAI) at any dose (MD -3.05; 95% CI -5.12, -0.98; p < 0.01; I2 = 19%) and at 2 mg (MD -4.36; 95% CI -7.02, -1.70; p < 0.01; I2 = 0%) over 12 weeks. Brexpiprazole at any dose and 2 mg also showed benefit in the Clinical Global Impression − Severity of illness (CGI-S) score as related to agitation over 12 weeks (MD -0.20; 95% CI -0.36, -0.05; p < 0.01; I2 = 35%). There is no significant difference between the groups in the incidence of at least one treatment-emergent adverse events (TEAEs; RR 1.14; 95% CI 0.95, 1.37; p = 0.16; I2 = 45%) and all-cause mortality (RR 1.99; 95% CI 0.37, 10.84; p = 0.42; I2 = 0%). Brexpiprazole at any dose significantly increased the Simpson-Angus Scale (SAS; MD 0.47; 95% CI 0.28, 0.66; p < 0.01). Our results suggest that brexpiprazole is more efficacious than placebo in the treatment of agitation in AD patients. Further studies are still necessary to confirm long-term effects of brexpiprazole. Prospero registry: CRD42023486694. [ABSTRACT FROM AUTHOR]

Aim: Brexpiprazole is the first FDA‐approved treatment for agitation associated with dementia due to Alzheimer's disease. Agitation in Alzheimer's dementia (AAD) occurs in high prevalence and is a great burden for patients and caregivers. Efficacy, safety, and tolerability of brexpiprazole were demonstrated in the AAD clinical trials. To demonstrate the agitation‐ameliorating effect of brexpiprazole in animals, we evaluated brexpiprazole in two AAD mouse models. Methods: The resident–intruder test was conducted in 5‐ to 6‐month‐old Tg2576 mice, given vehicle or brexpiprazole (0.01 or 0.03 mg/kg) orally 1 h before the test. Locomotor activity was measured in 6‐month‐old APPSL‐Tg mice given vehicle or brexpiprazole (0.01 or 0.03 mg/kg) orally the evening before the start of locomotor measurement for 3 days. Results: In the resident–intruder test, Tg2576 mice showed significantly higher attack number and shorter latency to first attack compared to non‐Tg mice. In the Tg mice, brexpiprazole treatment (0.03 mg/kg) significantly delayed the latency to first attack and showed a trend toward a decrease in attack number. APPSL‐Tg mice (≧6 months old) showed significantly higher locomotion during dark period Phase II (Zeitgeber time [ZT] 16–20) and Phase III (ZT20‐24) compared to non‐Tg mice, correlating with the clinical observations of late afternoon agitation in Alzheimer's disease. Brexpiprazole treatment (0.01 and 0.03 mg/kg) significantly decreased hyperlocomotion during the Phase III in APPSL‐Tg mice. Conclusion: The suppression of attack behavior and the reduction of nocturnal hyperlocomotion in these Tg mice may be indicative of the therapeutic effect of brexpiprazole on AAD, as demonstrated in the clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: The Cohen-Mansfield Agitation Inventory (CMAI) quantifies the frequency of agitation behaviors in elderly persons. This post hoc analysis of data from the brexpiprazole clinical program aimed to determine a meaningful within-patient change (MWPC) threshold for CMAI Total score among patients with agitation associated with dementia due to Alzheimer's disease. Methods: Data were included from three 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-arm trials of brexpiprazole for the treatment of agitation associated with dementia due to Alzheimer's disease (ClinicalTrials.gov identifiers: NCT01862640, NCT01922258, NCT03548584). Change in CMAI Total score (range 29-203; higher scores indicate higher frequency of agitation behaviors) from baseline to Week 12 was the primary endpoint in each trial. MWPC thresholds were estimated from anchor-based mean change analyses and receiver operating characteristic (ROC) curves. The Clinical Global Impression-Severity of illness (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scales, both as related to agitation, were used as anchors. Empirical cumulative distribution functions (eCDFs) and probability density functions (PDFs) were plotted as supportive evidence. Distributionbased methods were also employed. Results: Data from 898 patients were analyzed (mean age, 73.7years; mean baseline CMAI Total score, 73.8). The mean CMAI Total score change corresponding to a difference of small improvement vs. stable (CGI-S one-point decrease vs. no change), or minimally improved vs. no change (CGI-I rating of 3 vs. 4), ranged from -10.6 to -13.5 points. The mean CMAI Total score change corresponding to a difference of moderate improvement vs. stable (CGI-S two-point decrease vs. no change), or much improved vs. no change (CGI-I rating of 2 vs. 4), ranged from -20.2 to -25.7 points. ROC curve analyses generally produced smaller estimates of meaningful change. eCDFs and PDFs showed good distribution and separation of CMAI Total score change between CGI-S/CGI-I categories. In distribution-based analyses, the minimal detectable change for CMAI Total score (10.5-11.8 points) was generally lower than anchor-suggested thresholds. Conclusion: Triangulation of evidence from anchor- and distribution-based analyses supports an MWPC threshold for CMAI Total score of -20 points, with a threshold range of -15 to -25 points, in patients with agitation associated with dementia due to Alzheimer's disease. [ABSTRACT FROM AUTHOR]

The onset of psychotic symptoms occurs prior to age 19 in 39% of the patients with schizophrenia. There are limited approved treatment options for adolescents with schizophrenia. Brexpiprazole was approved by the United States Food and Drug Administration (FDA) for treatment of schizophrenia in adolescents in 2022. Extrapolation of adult data to youth and use of pharmacologic modeling coupled with open long-term safety data were used by the FDA to approve brexpiprazole for adolescent schizophrenia. They were all reviewed herein. D2 receptor partial agonist antipsychotic agents are preferred in the early phase of treatment of psychotic disorders. Approval of brexpiprazole in adolescent schizophrenia provides an additional option. Brexpiprazole was approved by the FDA on the basis of extrapolation of adult data without controlled trials in adolescents. This reduces placebo exposure in young people. Two previous agents (asenapine and ziprasidone) approved for adult schizophrenia failed to separate from placebo in adolescent schizophrenia studies; this partially undermines the process of extrapolation. For brexpiprazole, the paucity of data in adolescents relegates it to a second-line agent. More research on brexpiprazole is needed to delineate its relative role in the management of adolescent schizophrenia. [ABSTRACT FROM AUTHOR]

Abstract A novel antipsychotic medication named brexpiprazole (BRX) is currently employed for the treatment of schizophrenia and other psychotic disorders. Because BRX’s molecular structure includes a benzothiophene ring, it natively fluoresces. To detect BRX with precision and speed, a flow injection-fluorometric method, which is both sensitive and selective, is recommended. The fluorescence detection was conducted at 364 nm following excitation at 326 nm to capture the strong intrinsic fluorescence of BRX. The carrier solution employed was a mixture of phosphate buffer (pH 4, 10 mM) and acetonitrile (50: 50, v/v), with a flow rate of 0.5 mL min− 1. The calibration curve, based on peak areas, exhibited linearity within the concentration range of 20–350 ng mL− 1, with a remarkable correlation coefficient (r2) of 0.9999. The limit of quantitation was 9.7 ng mL− 1, and the limit of detection was found to be 3.2 ng mL− 1. This method was applied to quantify BRX in Neopression® tablets, achieving recovery within an acceptable range without interference from the tablet’s additives. Additionally, the proposed approach was successfully utilised to quantify the drug in spiked human plasma. The approach underwent validation following ICH requirements.

A novel antipsychotic medication named brexpiprazole (BRX) is currently employed for the treatment of schizophrenia and other psychotic disorders. Because BRX's molecular structure includes a benzothiophene ring, it natively fluoresces. To detect BRX with precision and speed, a flow injection-fluorometric method, which is both sensitive and selective, is recommended. The fluorescence detection was conducted at 364 nm following excitation at 326 nm to capture the strong intrinsic fluorescence of BRX. The carrier solution employed was a mixture of phosphate buffer (pH 4, 10 mM) and acetonitrile (50: 50, v/v), with a flow rate of 0.5 mL min− 1. The calibration curve, based on peak areas, exhibited linearity within the concentration range of 20–350 ng mL− 1, with a remarkable correlation coefficient (r2) of 0.9999. The limit of quantitation was 9.7 ng mL− 1, and the limit of detection was found to be 3.2 ng mL− 1. This method was applied to quantify BRX in Neopression® tablets, achieving recovery within an acceptable range without interference from the tablet's additives. Additionally, the proposed approach was successfully utilised to quantify the drug in spiked human plasma. The approach underwent validation following ICH requirements. [ABSTRACT FROM AUTHOR]

A pharmacokinetic (PK) bridging approach was successfully employed to support the dosing regimen and approval of brexpiprazole in pediatric patients aged 13‐17 years with schizophrenia. Brexpiprazole was approved in 2015 for the treatment of schizophrenia and the adjunctive treatment of major depressive disorder in adults based on efficacy and safety data from clinical trials. On January 13, 2020, the US Food and Drug Administration issued a general advice letter to sponsors highlighting the acceptance of efficacy extrapolation of certain atypical antipsychotics from adult patients to pediatric patients considering the similarity in disease and exposure–response relationships. Brexpiprazole is the first atypical antipsychotic approved in pediatrics using this approach. The PK data available from pediatric patients aged 13‐17 years have shown high variability due to the limited number of PK evaluable subjects, which limits a robust estimation of differences between adult and pediatric patients. The PK model‐based approach was thus utilized to evaluate the appropriateness of the dosing regimen by comparing PK exposures in pediatric patients aged 13‐17 years with exposures achieved in adults at the approved doses. In addition to exposure matching, safety data from a long‐term open‐label clinical study in pediatric patients informed the safety profile in pediatric patients. This report illustrates the potential of leveraging previously collected efficacy, safety, and PK data in adult patients to make a regulatory decision in pediatric patients for the indication of schizophrenia. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the effects of adjunctive brexpiprazole on patient life engagement and depressive symptoms in patients with major depressive disorder (MDD) using patient-reported outcomes. Methods: An 8-week, Phase 4, open-label, interventional study was conducted at 15 Canadian trial sites between April 2021 and May 2022. Adult outpatients with MDD (at least moderately severe) and inadequate response to 1–2 antidepressants continued their current antidepressant and received oral adjunctive brexpiprazole 0.5–2 mg/day. Co-primary endpoints were change from baseline to Week 8 in Inventory of Depressive Symptomatology Self-Report (IDS-SR) 10-item Life Engagement subscale score, and IDS-SR 30-item total score. Safety was assessed by standard variables. Results: Of 122 enrolled patients, 120 (98.4%) were treated (mean [ SD ] dose: 1.2 [0.4] mg/day) and analyzed, and 111 (91.0%) completed the study. Statistically significant least squares mean improvements to Week 8 were observed on IDS-SR10 Life Engagement subscale score (baseline mean [ SD ]: 16.1 [4.7]; change [95% confidence interval]: −8.11 [−9.34, −6.88]; p < 0.001) and IDS-SR total score (baseline mean [ SD ]: 41.3 [9.8]; change [95% confidence interval]: −17.38 [−20.08, −14.68]; p < 0.001). Improvements were observed from Week 2, onwards. Treatment-emergent adverse events with incidence ≥5% were fatigue (n = 13, 10.8%), headache (n = 13, 10.8%), insomnia (n = 12, 10.0%), nausea (n = 9, 7.5%), tremor (n = 8, 6.7%), and weight increase (n = 7, 5.8%). Six patients (5.0%) discontinued due to adverse events. Mean (SD) change in body weight from baseline to last visit was +1.9 (3.4) kg. Conclusions: Using an exploratory patient-reported outcome measure, patients with MDD and inadequate response to antidepressants who received open-label adjunctive brexpiprazole showed early and clinically meaningful improvement in patient life engagement, which should be further assessed in a prospective randomized controlled trial. Patient-rated depressive symptoms (on the validated 30-item IDS-SR) also improved. Adjunctive brexpiprazole was well tolerated, and no new safety signals were observed. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT04830215. [ABSTRACT FROM AUTHOR]

Since the 1950s, there have been rapid developments in psychiatric pharmacotherapy, resulting not only in more effective treatment of patients, but also in improvements in mini-mizing adverse effects of therapy. Modern third-generation antipsychotics, in addition to antagonism toward D2 receptors, also exhibit partial agonism toward dopamine receptors. Such a mechanism of action is intended to regulate dopaminergic transmission - inhibit (antagonism) it in pathways where it is excessive (excessive transmission in the mesolimbic pathway in psychotic patients, excessive transmission in the tuberoinfundibular pathway in patients with hyperprolactinemia) and stimulate (agonism) it in pathways where it is too low (mesocortical pathway). This has a beneficial effect on both the reduction of adverse symptoms and the negative, affective and cognitive symptoms of patients suffering from schizophrenia. The purpose of this review article is to present the most important clinical aspects of the use of dopamine D2 receptor partial agonists in the treatment of schizophrenia, using brexpiprazole as an example, and to define the profile of patients to whom this drug could be dedicated - based on recent studies. [ABSTRACT FROM AUTHOR]

Abstract Aim This systematic review and frequentist network meta‐analysis used random‐effects models is conducted to determine whether there are differences in the efficacy, acceptability, tolerability, and safety profiles of brexpiprazole (BRE) and aripiprazole (ARI) for Japanese with major depressive disorder (MDD) who were inadequately responsive to antidepressants. Methods Outcome measures were scores on the Montgomery Åsberg Depression Rating Scale (primary), the Clinical Global Impression severity scale, and social functioning scale; the non‐response rate; the non‐remission rate; all‐cause discontinuation; discontinuation due to adverse events (DAE); at least one adverse event (1AE); serious adverse event, akathisia; tremor; weight gain. Results A literature search identified three double‐blind, randomized, placebo‐controlled trials. These comprised one BRE study (with a 1 mg/day [BRE1] and a 2 mg/day [BRE2]) and two ARI studies (with a 3 mg/day arm and a flexible‐dose arm[within the dosage range approved in Japan]) (n = 1736). Both BRE and ARI demonstrated better efficacy than the placebo. BRE but not ARI had a higher DAE than the placebo. ARI but not BRE had a higher 1AE than the placebo. BRE and ARI had a higher risk of akathisia and weight gain than the placebo. There were no significant differences between BRE and ARI for any of the outcomes. Although BRE1 had good efficacy, it carried risk of weight gain. Although BRE2 also had efficacy, it carried risks of DAE, akathisia, and weight gain. However, the risk of akathisia in BRE2 was reduced by an initial dose of 0.5 mg/day rather than 1.0 mg/day. Conclusions Overall BRE showed similar utility to ARI and a good risk–benefit balance.

A novel and industrially viable process was developed to synthesize Brexpiprazole an antipsychotic drug. This process involves using 1,4-butanediol as a key starting material, which is then diprotected and subsequently reacted with 7-hydroxy-2(1H)-quinolinone and piperazine-l-benzo[b]thien-4-y1 hydrochloride using potassium carbonate as a base, resulting in a novel intermediate, the spiro-tosyl salt, with a good yield and purity. Various conditions, solvents and bases were evaluated to optimize the coupling reaction of tosyl salt with 7-Hydroxy-2-(1H)-Quinolinone. Finally, we have chosen Sodium carbonate as a base and selected N,N-dimethylacetamide as a solvent. The reaction was carried at an elevated temperature, resulting in the production of Brexpiprazole with good yield and excellent purity. The product is fully characterized by using analytical methods like 1H NMR, 13C NMR, HPLC and HRMS analysis. [ABSTRACT FROM AUTHOR]

Background: Dual disorders (DDs) involve the coexistence of a substance use disorder (SUD) with another mental illness, often from the psychotic and affective categories. They are quite common in clinical practice and present significant challenges for both diagnosis and treatment. This study explores the effectiveness of brexpiprazole, a third-generation antipsychotic, in an Italian sample of individuals diagnosed with schizophrenia spectrum disorder and a comorbid SUD. Methods: Twenty-four patients, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and enrolled in several Italian hospitals, underwent a psychometric assessment at baseline (T0) and one month (T1) after starting brexpiprazole treatment administered at a mean dosage of 2 mg/day. Results: Brexpiprazole demonstrated significant reductions in psychopathological burden (Positive and Negative Syndrome Scale/PANSS total score: p < 0.001). Positive (p = 0.003) and negative (p = 0.028) symptoms, substance cravings (VAS craving: p = 0.039), and aggression (MOAS scale: p = 0.003) were notably reduced. Quality of life improved according to the 36-item Short Form Health Survey (SF-36) subscales (p < 0.005). Conclusions: This study provides initial evidence supporting brexpiprazole's efficacy and safety in this complex patient population, with positive effects not only on psychopathology and quality of life, but also on cravings. Further studies involving larger cohorts of subjects and extended follow-up periods are needed. [ABSTRACT FROM AUTHOR]

Brexpiprazole is a new antipsychotic drug from the group of dopamine D2/D3 receptor partial agonists. It represents a development of the second-generation antipsychotics and is an important addition to the pharmacological treatment options for schizophrenia The purpose of this article is to present, illustrated by the case of brexpiprazole, how advances in the pharmacological properties of new antipsychotics translate into improved results in the treatment of schizophrenia, not only in terms of symptom reduction, but also in terms of functional improvement. The ratio of activation to blocking of the D2/D3 receptor is lower for brexpiprazole than for aripiprazole and cariprazine, which may translate into a lower risk of akathisia. Brexpiprazole has also stronger antihistaminic activity, which is likely to be associated with a stronger sedative effect, a lower risk of akathisia, excessive agitation and insomnia. Brexpiprazole meets the traditional requirements for an antipsychotic drug's efficacy, i.e., compared to placebo, it brings a greater reduction in schizophrenia symptoms in short-term studies and prevents schizophrenia relapses in long-term follow-up. The highest antipsychotic efficacy was found with the highest registered dose (4 mg/day). In addition to reducing positive symptoms, brexpiprazole treatment also leads to a reduction in negative and depressive symptoms, as well as anxiety. It has also a positive effect on patients' social and personal functioning and quality of life. This action of the drug is in line with the expectations of patients and their families regarding effective treatment. It should not only reduce symptoms, but also enable a return to health, i.e., a state that, in addition to optimal health and a sense of psychological well-being, also makes it possible to maintain proper social relations. [ABSTRACT FROM AUTHOR]