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https://www.readbyqxmd.com/read/29152847/a-case-study-in-identifying-targeted-patients-population-in-major-depressive-disorder-by-enhanced-enrichment-design
#1
Peter Zhang, Kevin Carroll, Mary Hobart, Carole Augustine, Gary Koch
Despite advances in clinical trial design, failure rates near 80% in phase 2 and 50% in phase 3 have recently been reported. The challenges to successful drug development are particularly acute in central nervous system trials such as for pain, schizophrenia, mania, and depression because high-placebo response rates lessen assay sensitivity, diminish estimated treatment effect sizes, and thereby decrease statistical power. This paper addresses the importance of rigorous patient selection in major depressive disorder trials through an enhanced enrichment paradigm...
November 19, 2017: Pharmaceutical Statistics
https://www.readbyqxmd.com/read/29128144/the-antipsychotic-drug-brexpiprazole-reverses-phencyclidine-induced-disruptions-of-thalamocortical-networks
#2
Hanna E van den Munkhof, Jørn Arnt, Pau Celada, Francesc Artigas
Brexpiprazole (BREX), a recently approved antipsychotic drug in the US and Canada, improves cognitive dysfunction in animal models, by still largely unknown mechanisms. BREX is a partial agonist at 5-HT1A and D2 receptors and antagonist at α1B- and α2C-adrenergic and 5-HT2A receptors all with a similar potency. The NMDA receptor antagonist phencyclidine (PCP), used as pharmacological model of schizophrenia, activates thalamocortical networks and decreases low frequency oscillations (LFO; <4 Hz). These effects are reversed by antipsychotics...
November 8, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29109605/brexpiprazole-for-schizophrenia
#3
REVIEW
(no author information available yet)
No abstract text is available yet for this article.
October 2017: Australian Prescriber
https://www.readbyqxmd.com/read/29055257/efficacy-of-adjunctive-brexpiprazole-on-the-core-symptoms-of-major-depressive-disorder-a-post-hoc-analysis-of-two-pooled-clinical-studies
#4
J Craig Nelson, Emmanuelle Weiller, Peter Zhang, Catherine Weiss, Mary Hobart
BACKGROUND: Patients with major depressive disorder (MDD) who do not adequately respond to antidepressant treatment (ADT) may benefit from adjunctive atypical antipsychotics; however, certain agents target specific symptoms of depression and not the full syndrome. The aim of this analysis was to examine the effects of brexpiprazole, adjunct to ADT, on the core symptoms of MDD, defined using Montgomery-Åsberg Depression Rating Scale (MADRS) items. METHODS: This was a post hoc analysis of data from two 6-week, randomized, double-blind studies of adjunctive brexpiprazole in patients with MDD and inadequate response to ADTs (n = 1056)...
September 29, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29017334/brexpiprazole-a-new-leaf-on-the-partial-dopamine-agonist-branch
#5
Judy Hope, David Castle, Nicholas A Keks
OBJECTIVES: Brexpiprazole is a new dopamine partial agonist antipsychotic in the same class as aripiprazole. This paper will briefly review brexpiprazole and compare it with aripiprazole. CONCLUSIONS: Brexpiprazole and aripiprazole are both partial agonists at dopamine D2, and serotonin 5-HT1A and antagonists at serotonin 5-HT2A and noradrenergic α1B receptors. However, the two drugs are significantly different in potencies at various receptors; neurochemical profiles predict that brexpiprazole may be comparable with aripiprazole in its antipsychotic efficacy but may cause less akathisia, extrapyramidal side effects (EPS) and activation...
October 1, 2017: Australasian Psychiatry: Bulletin of Royal Australian and New Zealand College of Psychiatrists
https://www.readbyqxmd.com/read/28828976/brexpiprazole-a-partial-dopamine-agonist-for-the-treatment-of-schizophrenia
#6
Asli Ekinci, Okan Ekinci
BACKGROUND: Schizophrenia is a chronic and debilitating mental disorder that affects the patient's and their family's life. The disease remains a complicated disorder that is challenging to treat, despite there being a large antipsychotic armamentarium. Brexpiprazole acts both as a partial agonist at the serotonin 5-HT1A and dopamine D2 receptors and as an antagonist at the serotonin 5-HT2A and noradrenaline alpha1B and alpha2C receptors, all with similar potency. This balanced receptor profile may produce promising antipsychotic effects on positive, negative and cognitive symptoms in schizophrenia with minimal adverse effects...
August 20, 2017: Reviews on Recent Clinical Trials
https://www.readbyqxmd.com/read/28750151/pharmacokinetics-and-safety-of-brexpiprazole-following-multiple-dose-administration-to-japanese-patients-with-schizophrenia
#7
Jun Ishigooka, Shuichi Iwashita, Koushi Higashi, Ei Leen Liew, Yoshihiro Tadori
Brexpiprazole is currently approved in the United States for the treatment of schizophrenia and as adjunctive treatment of major depressive disorder. In Canada, it is approved for the treatment of schizophrenia. This study evaluated the pharmacokinetics (PK) and safety of brexpiprazole in Japanese patients with schizophrenia. This phase 1 study comprised a 14-day multiple-dose administration of brexpiprazole 1, 4, and 6 mg/day (n = 7, 8, and 6, respectively). Plasma concentrations and PK parameters and the influence of CYP2D6 polymorphisms (intermediate metabolizers [IMs] and extensive metabolizers [EMs]) on PK were evaluated...
July 27, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28748374/alterations-in-amino-acid-levels-in-mouse-brain-regions-after-adjunctive-treatment-of-brexpiprazole-with-fluoxetine-comparison-with-r-ketamine
#8
Min Ma, Qian Ren, Yuko Fujita, Chun Yang, Chao Dong, Yuta Ohgi, Takashi Futamura, Kenji Hashimoto
RATIONALE: Brexpiprazole, a serotonin-dopamine activity modulator, is approved in the USA as an adjunctive therapy to antidepressants for treating major depressive disorders. Similar to the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine, the combination of brexpiprazole and fluoxetine has demonstrated antidepressant-like effects in animal models of depression. OBJECTIVES: The present study was conducted to examine whether the combination of brexpiprazole and fluoxetine could affect the tissue levels of amino acids [glutamate, glutamine, γ-aminobutyric acid (GABA), D-serine, L-serine, and glycine] that are associated with NMDAR neurotransmission...
November 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28721057/safety-tolerability-and-risks-associated-with-first-and-second-generation-antipsychotics-a-state-of-the-art-clinical-review
#9
REVIEW
Marco Solmi, Andrea Murru, Isabella Pacchiarotti, Juan Undurraga, Nicola Veronese, Michele Fornaro, Brendon Stubbs, Francesco Monaco, Eduard Vieta, Mary V Seeman, Christoph U Correll, André F Carvalho
Since the discovery of chlorpromazine (CPZ) in 1952, first-generation antipsychotics (FGAs) have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large numbers of patients with severe mental illness (SMI) to be treated in the community. Second-generation antipsychotics (SGAs) ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients - psychosocial functioning, quality of life, and recovery...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28718334/the-preclinical-discovery-and-development-of-brexpiprazole-for-the-treatment-of-major-depressive-disorder
#10
REVIEW
Awais Aftab, Keming Gao
Brexpiprazole is the most recently approved second-generation antipsychotic, which is used as adjunctive therapy to antidepressants for treating major depressive disorder (MDD) with inadequate response. Brexpiprazole shares pharmacological similarities with other second-generation antipsychotics, especially aripiprazole. Area covered: This review provides a detailed overview of the pre-clinical studies of brexpiprazole, followed by a summary of its clinical studies, and a comparison with other antipsychotics in MDD...
October 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28539103/possible-oxcarbazepine-inductive-effects-on-aripiprazole-metabolism-a-case-report
#11
Ian R McGrane, Joshua G Loveland, Jose de Leon
Oxcarbazepine is a cytochrome P450 (CYP) 3A4 inducer, which is structurally similar to carbamazepine. Although lacking Food and Drug Administration approval, oxcarbazepine is sometimes prescribed to treat aggressive behavior in youth with autism spectrum disorder (ASD). These youths may also be taking second-generation antipsychotics, some of which are substrates of the CYP3A4 metabolic pathway. The combination of these medications may result in decreased serum antipsychotic concentrations, potentially reducing effectiveness...
January 1, 2017: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/28443355/investigational-dopamine-antagonists-for-the-treatment-of-schizophrenia
#12
REVIEW
Sheng-Min Wang, Changsu Han, Soo-Jung Lee, Tae-Youn Jun, Ashwin A Patkar, Prakash S Masand, Chi-Un Pae
Schizophrenia is a debilitating illness with a chronic impact on social function and daily living. Although various antipsychotics are available, there are still many challenges and unmet needs. Thus, many compounds with diverse mechanisms have been investigated, but all approved antipsychotics still require interactions with dopamine D2 receptors. Areas covered: We searched for investigational drugs using the key words 'dopamine' and 'schizophrenia' in American and European clinical trial registers (clinicaltrials...
June 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28351543/corrigendum-to-efficacy-of-brexpiprazole-in-patients-with-acute-schizophrenia-review-of-three-randomized-double-blind-placebo-controlled-studies-schizophr-res-174-2016-82-92
#13
Christoph U Correll, Aleksandar Skuban, Mary Hobart, John Ouyang, Emmanuelle Weiller, Catherine Weiss, John M Kane
No abstract text is available yet for this article.
March 25, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28331332/clinical-role-of-brexpiprazole-in-depression-and-schizophrenia
#14
REVIEW
Nishant B Parikh, Diana M Robinson, Anita H Clayton
Brexpiprazole, a serotonin-dopamine activity modulator, is the second D2 partial agonist to come to market and has been approved for the treatment of schizophrenia and as an adjunctive treatment in major depressive disorder. With less intrinsic activity than aripiprazole at the D2 receptor and higher potency at 5-HT2A, 5-HT1A, and α1B receptors, the pharmacological properties of brexpiprazole suggest a more tolerable side effect profile with regard to akathisia, extrapyramidal dysfunction, and sedation. While no head-to-head data are currently available, double-blind placebo-controlled studies show favorable results, with the number needed to treat (NNT) vs placebo of 6-15 for response in acute schizophrenia treatment and 4 for maintenance...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28317392/pharmacotherapy-of-major-depression-in-late-life-what-is-the-role-of-new-agents
#15
REVIEW
Kinjal Patel, Petal S Abdool, Tarek K Rajji, Benoit H Mulsant
Evidence on the pharmacotherapy of late-life major depressive disorder (LLD) is scant. Most of the recommendations in existing clinical guidelines are based on expert opinions, extrapolations from data obtained in younger patients, or theoretical considerations. Areas covered: This article summarizes the recommendations from existing clinical guidelines and recent reviews on the treatment of LLD. Next, it discusses the potential role of newer antidepressants - vilazodone, levomilnacipran, and vortioxetine - based on a systematic search of the literature published during the past five years...
April 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28300462/an-update-on-the-advancements-in-the-treatment-of-agitation-in-alzheimer-s-disease
#16
REVIEW
Anton P Porsteinsson, Inga M Antonsdottir
Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are associated with significant negative outcomes for patients and their caregivers. Agitation, one of the most distressing NPS, lacks safe and effective long term interventions. Nonpharmacological interventions are suggested as first-line treatment, but aren't effective for every patient, resulting in pharmacological interventions for some patients, consisting of off-label use of antipsychotics, sedative/hypnotics, anxiolytics, acetylcholinesterase inhibitors, memantine, and antidepressants; where efficacy doesn't necessarily outweigh associated risks...
April 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28228056/brexpiprazole
#17
REVIEW
Marija Markovic, Alyssa Gallipani, Krina H Patel, Megan Maroney
OBJECTIVE: To review the pharmacology and clinical data for brexpiprazole in schizophrenia and major depressive disorder (MDD). DATA SOURCES: An English-language literature search using PubMed and MEDLINE was performed using the term brexpiprazole. All articles containing human clinical trial data published up to September 2016 were evaluated for inclusion as well as information from the manufacturer's product labeling. STUDY SELECTION/DATA EXTRACTION: Phase 3 trials for brexpiprazole were evaluated...
April 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28195853/efficacy-of-brexpiprazole-as-adjunctive-treatment-in-major-depressive-disorder-with-irritability-post-hoc-analysis-of-2-pivotal-clinical-studies
#18
Maurizio Fava, Emmanuelle Weiller, Peter Zhang, Catherine Weiss
No abstract text is available yet for this article.
April 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28190661/the-novel-antipsychotic-drug-brexpiprazole-alone-and-in-combination-with-escitalopram-facilitates-prefrontal-glutamatergic-transmission-via-a-dopamine-d1-receptor-dependent-mechanism
#19
Carl Björkholm, Monica M Marcus, Åsa Konradsson-Geuken, Kent Jardemark, Torgny H Svensson
Brexpiprazole (Rexulti(®)), a novel D2/3 receptor (R) partial agonist, was recently approved as monotherapy for schizophrenia, demonstrating effectiveness against both positive and negative symptoms, and also approved as add-on treatment to antidepressant drugs, inducing a potent antidepressant effect with a faster onset compared to an antidepressant given alone. Moreover, brexpiprazole has demonstrated pro-cognitive effects in preclinical studies. To explore whether the observed effects may be mediated via modulation of prefrontal glutamatergic transmission, we investigated the effect of brexpiprazole, alone and in combination with the SSRI escitalopram, on prefrontal glutamatergic transmission using in vitro electrophysiological intracellular recordings of deep layer pyramidal cells of the rat medial prefrontal cortex (mPFC)...
April 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28160035/brexpiprazole-reduces-hyperactivity-impulsivity-and-risk-preference-behavior-in-mice-with-dopamine-transporter-knockdown-a-model-of-mania
#20
Morgane Milienne-Petiot, Mark A Geyer, Jørn Arnt, Jared W Young
RATIONALE: Bipolar disorder (BD) is a unique mood disorder defined by periods of depression and mania. The defining diagnosis of BD is the presence of mania/hypomania, with symptoms including hyperactivity and risk-taking. Since current treatments do not ameliorate cognitive deficits such as risky decision-making, and impulsivity that can negatively affect a patient's quality of life, better treatments are needed. OBJECTIVES: Here, we tested whether acute treatment with brexpiprazole, a serotonin-dopamine activity modulator with partial agonist activity at D2/3 and 5-HT1A receptors, would attenuate the BD mania-relevant behaviors of the dopamine transporter (DAT) knockdown mouse model of mania...
March 2017: Psychopharmacology
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