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Brexpiprazole: so far so good.

ABSTRACT: This article describes the role of a newly approved antipsychotic agent brexpiprazole in the treatment of schizophrenia and major depressive disorder. This drug has high affinity for 5-HT1A, 5-HT2A, D2 and ?1B,2C receptors. It displays partial agonism at 5-HT1A and D2 receptors and potent antagonism at 5-HT2A and ?1B,2C adrenergic receptors. It also has some affinity (antagonism) for D3, 5-HT2B, 5-HT7 and ?1A,1D receptors, and moderate affinity for H1 and low affinity for M1 receptors. These all lead to a favorable antipsychotic profile in terms of improvement of cognitive performance and sleep patterns, as well as effects on affective states and potential to treat core symptoms in schizophrenia and major depressive disorder, including cognitive deficits with a low risk of adverse effects (extrapyramidal symptoms, metabolic complications, weight gain, akathisia potential) that are commonly encountered with other typical and second-generation antipsychotic drugs. In our review, we have made an attempt to decipher the pharmacological profile of brexpiprazole from two major trials (VECTOR and BEACON). We have also tried to give a concise but detailed overview of brexpiprazole by head to head comparison of the pharmacological profile of brexpiprazole and its earlier congeners aripiprazole and prototype antipsychotic drug chlorpromazine by accessing individual summaries of product characteristics from the US Food and Drug Administration database, 2015. Relevant preclinical and clinical studies associated with this drug have been discussed with emphasis on efficacy and safety concerns. From the studies done so far, it can be concluded that brexpiprazole can be an effective monotherapy for schizophrenia and as an adjunct to other antidepressant medications in major depressive disorder.

SUBMITTER: Das S

PROVIDER: S-EPMC4749739 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Brexpiprazole: so far so good.

Das Saibal S Barnwal Preeti P Winston A Blessed B Mondal Somnath S Saha Indranil I

Therapeutic advances in psychopharmacology 20160201 1

This article describes the role of a newly approved antipsychotic agent brexpiprazole in the treatment of schizophrenia and major depressive disorder. This drug has high affinity for 5-HT1A, 5-HT2A, D2 and α1B,2C receptors. It displays partial agonism at 5-HT1A and D2 receptors and potent antagonism at 5-HT2A and α1B,2C adrenergic receptors. It also has some affinity (antagonism) for D3, 5-HT2B, 5-HT7 and α1A,1D receptors, and moderate affinity for H1 and low affinity for M1 receptors. These all ...[more]

PMID: 26913177

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Project description:This paper aims to illustrate the steps needed to produce reliable correlative modelling for arthropod vectors, when process-driven models are unavailable. We use ticks as examples because of the (re)emerging interest in the pathogens they transmit. We argue that many scientific publications on the topic focus on: (i) the use of explanatory variables that do not adequately describe tick habitats; (ii) the automatic removal of variables causing internal (statistical) problems in the models without considering their ecological significance; and (iii) spatial pattern matching rather than niche mapping, therefore losing information that could be used in projections.We focus on extracting information derived from modelling the environmental niche of ticks, as opposed to pattern matching exercises, as a first step in the process of identifying the ecological determinants of tick distributions. We perform models on widely reported species of ticks in Western Palaearctic to derive a set of covariates, describing the climate niche, reconstructing a Fourier transformation of remotely-sensed information.We demonstrate the importance of assembling ecological information that drives the distribution of ticks before undertaking any mapping exercise, from which this kind of information is lost. We also show how customised covariates are more relevant to tick ecology than the widely used set of "Bioclimatic Indicators" ("Biovars") derived from interpolated datasets, and provide programming scripts to easily calculate them. We demonstrate that standard pre-tailored vegetation categories also fail to describe tick habitats and are best used to describe absence rather than presence of ticks, but could be used in conjunction with the climate based suitability models.We stress the better performance of climatic covariates obtained from remotely sensed information as opposed to interpolated explanatory variables derived from ground measurements which are flawed with internal issues affecting modelling performance. Extracting ecological conclusions from modelling projections is necessary to gain information about the variables driving the distribution of arthropod vectors. Mapping exercises should be a secondary aim in the study of the distribution of health threatening arthropods.

Project description:Although there is a consensus about the evolutionary drivers of animal migration, considerable work is necessary to identify the mechanisms that underlie the great variety of strategies observed in nature. The study of differential migration offers unique opportunities to identify such mechanisms and allows comparisons of the costs and benefits of migration. The purpose of this study was to compare the characteristics of short and long-distance migrations, and fitness consequences, in a long-lived seabird species. We combined demographic monitoring (survival, phenology, hatching success) of 58 Northern Gannets (Morus bassanus) breeding on Bonaventure Island (Canada) and biologging technology (Global Location Sensor or GLS loggers) to estimate activity and energy budgets during the non-breeding period for three different migration strategies: to the Gulf of Mexico (GM), southeast (SE) or northeast (NE) Atlantic coast of the U.S. Survival, timing of arrival at the colony and hatching success are similar for short (NE, SE) and long-distance (GM) migrants. Despite similar fitness consequences, we found, as expected, that the overall energetic cost of migration is higher for long-distance migrants, although the daily cost during migration was similar between strategies. In contrast, daily maintenance and thermoregulation costs were lower for GM migrants in winter, where sea-surface temperature of the GM is 4-7o C warmer than SE and NE. In addition, GM migrants tend to fly 30 min less per day in their wintering area than other migrants. Considering lower foraging effort and lower thermoregulation costs during winter for long-distance migrants, this suggests that the energetic benefits during the winter of foraging in the GM outweigh any negative consequences of the longer-distance migration. These results support the notion that the costs and benefits of short and long-distance migration is broadly equal on an annual basis, i.e. there are no apparent carry-over effects in this long-lived bird species, probably because of the favourable conditions in the furthest wintering area.

Project description:ImportanceAgitation is a prevalent, distressing, and burdensome manifestation of Alzheimer dementia in need of an efficacious, safe, and well-tolerated treatment.ObjectiveTo confirm the efficacy, safety, and tolerability of brexpiprazole in patients with agitation in Alzheimer dementia.Design, setting, and participantsThis randomized clinical trial was a 12-week, double-blind, placebo-controlled, fixed-dose, parallel-arm trial that ran from May 2018 to June 2022 at 123 clinical trial sites in Europe and the United States. Participants included patients with agitation in Alzheimer dementia in a care facility or community-based setting. Stable Alzheimer disease medications were permitted.InterventionsIn this 2-arm trial, patients were randomized to receive oral brexpiprazole or placebo (2:1 ratio) for 12 weeks. Within the brexpiprazole arm, patients were further randomized to receive fixed doses of 2 mg/d or 3 mg/d in a 1:2 ratio.Main outcomes and measuresThe primary end point was change in Cohen-Mansfield Agitation Inventory total score (which measures the frequency of 29 agitated behaviors) from baseline to week 12 for brexpiprazole, 2 or 3 mg, vs placebo. Safety was assessed by standard measures, including treatment-emergent adverse events.ResultsA total of 345 patients were randomized to receive brexpiprazole (n = 228) or placebo (n = 117); completion rates were 198 (86.8%) for brexpiprazole and 104 (88.9%) for placebo. Mean (SD) age was 74.0 (7.5) years, and 195 of 345 patients were female (56.5%). Patients receiving brexpiprazole, 2 or 3 mg (n = 225), demonstrated statistically significantly greater improvement than those taking placebo (n = 116) in Cohen-Mansfield Agitation Inventory total score from baseline to week 12 (brexpiprazole baseline, 80.6, mean change, -22.6; placebo baseline, 79.2, mean change, -17.3; least-squares mean difference, -5.32; 95% CI, -8.77 to -1.87; P = .003; Cohen d effect size, 0.35). No treatment-emergent adverse events had an incidence of 5% or more with brexpiprazole and greater incidence than placebo. The proportion of patients who discontinued because of adverse events was 12 of 226 (5.3%) for brexpiprazole and 5 of 116 (4.3%) for placebo.Conclusions and relevanceIn this study, patients with Alzheimer dementia who took brexpiprazole, 2 or 3 mg, showed a statistically significant improvement vs placebo in agitation over 12 weeks. Brexpiprazole was generally well tolerated over 12 weeks in this vulnerable patient population.Trial registrationClinicalTrials.gov Identifier: NCT03548584.

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Brexpiprazole: so far so good.

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Brexpiprazole: so far so good.

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