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https://www.readbyqxmd.com/read/29790360/-current-and-future-pharmacotherapy-of-severe-psychiatric-disorders
#1
Eva Češková
Despite of tremendous development in CNS research, current treatment is suboptimal especially in severe mental disorders. In medicine, there are two main methods of improving the healthcare provided: seeking new treatment procedures and perfecting (optimizing) the existing ones. Optimization of treatment includes not only practical tools such as therapeutic drug monitoring, but also implementation of general trends into the clinical practice. New pharmacological options include drugs aimed at other than monoaminergic systems and old drugs used before the psychopharmacological era...
2018: Casopís Lékar̆ů C̆eských
https://www.readbyqxmd.com/read/29774628/efficacy-and-safety-of-brexpiprazole-for-the-treatment-of-acute-schizophrenia-in-japan-a-6-week-randomized-double-blind-placebo-controlled-study
#2
Jun Ishigooka, Shuichi Iwashita, Yoshihiro Tadori
AIMS: This study aimed to evaluate the efficacy, safety, and tolerability of brexpiprazole compared to placebo in Japanese patients with acute schizophrenia. METHODS: We conducted a 6-week, multicenter, double-blind, placebo-controlled, phase 2/3 study in Japan. Patients with acute schizophrenia were randomized (1:1:1:1) to receive brexpiprazole 1, 2, or 4 mg or placebo once a day. The primary endpoint was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total scores...
May 18, 2018: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/29698737/dichlorophenyl-piperazines-including-a-recently-approved-atypical-antipsychotic-are-potent-inhibitors-of-dhcr7-the-last-enzyme-in-cholesterol-biosynthesis
#3
Thiago C Genaro-Mattos, Keri A Tallman, Luke B Allen, Allison Anderson, Karoly Mirnics, Zeljka Korade, Ned A Porter
While antipsychotic medications provide important relief from debilitating psychotic symptoms, they also have significant adverse side effects, which might have relevant impact on human health. Several research studies, including ours, have shown that commonly used antipsychotics such as haloperidol and aripiprazole affect cholesterol biosynthesis at the conversion of 7-dehydrocholesterol (7-DHC) to cholesterol. This transformation is promoted by the enzyme DHCR7 and its inhibition causes increases in plasma and tissue levels of 7-DHC...
April 23, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29697278/efficacy-and-metabolic-effects-of-lurasidone-versus-brexpiprazole-in-schizophrenia-a-network-meta-analysis
#4
Daisy Ng-Mak, Vanita Tongbram, Kerigo Ndirangu, Krithika Rajagopalan, Antony Loebel
AIM: To assess the relative efficacy and metabolic effects of lurasidone and brexpiprazole in the acute treatment of schizophrenia. METHODS: Five lurasidone and three brexpiprazole trials were identified. In the absence of head-to-head trials, a Bayesian network meta-analysis comparing lurasidone and brexpiprazole was performed. RESULTS: Nonstatistically significant differences in efficacy measures were observed between lurasidone and brexpiprazole...
April 26, 2018: Journal of Comparative Effectiveness Research
https://www.readbyqxmd.com/read/29582518/long-term-safety-and-effectiveness-of-brexpiprazole-in-japanese-patients-with-schizophrenia-a-52-week-open-label-study
#5
Jun Ishigooka, Shuichi Iwashita, Yoshihiro Tadori
AIMS: This study assessed the long-term safety, tolerability and maintenance of the therapeutic effect of brexpiprazole in Japanese patients with schizophrenia. METHODS: This 52-week, open-label, flexible-dose (1-4 mg/day) study included patients with schizophrenia who continued treatment from a short-term randomized placebo-controlled fixed-dose (1, 2, or 4 mg/day) trial and de novo patients who switched from other antipsychotics. RESULTS: A total of 282 patients (184 de novo and 98 rolled over from short-term trial) entered the 52-week treatment with brexpiprazole, and 150 (53...
March 26, 2018: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/29559781/novel-treatment-options-in-depression-and-psychosis
#6
REVIEW
Eva Ceskova, Petr Silhan
In spite of tremendous development in central nervous system research, current treatment is suboptimal, especially in severe mental disorders. In medicine, there are two main methods of improving the health care provided: seeking new treatment procedures and perfecting (optimizing) the existing ones. Optimization of treatment includes not only practical tools such as therapeutic drug monitoring but also implementation of general trends in the clinical practice. New pharmacological options include new more sophisticated forms of monoaminergic drugs, old drugs rediscovered on the base of a better understanding of pathophysiology of mental illnesses, and drugs aimed at new treatment targets...
2018: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/29543103/meta-analysis-and-review-of-dopamine-agonists-in-acute-episodes-of-mood-disorder-efficacy-and-safety
#7
Bruno Romeo, Lisa Blecha, Katia Locatelli, Amine Benyamina, Catherine Martelli
The objective of this meta-analysis is to assess the efficacy and safety of partial and complete dopamine agonists in the treatment of acute mood disorder episodes. Randomized, double-blind and placebo-controlled trials of dopamine agonists in the treatment of acute mood disorder episodes were identified in the MEDLINE and PsycINFO databases and included in the meta-analysis. In monotherapy of mania, improved remission rates were found for cariprazine (odds ratio (OR): 2.08, P < 0.01) and for high-dose aripiprazole (OR: 3...
April 2018: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29427512/the-use-of-brexpiprazole-amongst-individuals-with-insufficient-outcomes-with-aripiprazole-or-bupropion-a-case-series
#8
Traci Aladeen, Erica Westphal, Yena Lee, Carola Rong, Michelle Rainka, Horacio Capote, Roger S McIntyre
PURPOSE: We sought to characterize the clinical experience of outpatients treated with brexpiprazole after achieving suboptimal outcomes with aripiprazole or bupropion as determined by the treating psychiatric provider. DESIGN AND METHODS: Case series; inefficacy, intolerability, or other unsatisfactory outcome to previous trial with aripiprazole or bupropion. FINDINGS: The majority of individuals in our sample exhibited tolerability of brexpiprazole...
February 10, 2018: Perspectives in Psychiatric Care
https://www.readbyqxmd.com/read/29415258/a-long-term-open-label-study-to-evaluate-the-safety-and-tolerability-of-brexpiprazole-as-maintenance-treatment-in-adults-with-schizophrenia
#9
Andy Forbes, Mary Hobart, John Ouyang, Lily Shi, Stephanie Pfister, Mika Hakala
Background: Brexpiprazole is a serotonin-dopamine activity modulator with efficacy in acute schizophrenia and relapse prevention. The aim of this Phase 3, multicenter study was to assess the long-term safety, tolerability, and efficacy of treatment with brexpiprazole flexible-dose 1-4 mg/day. Methods: Patients rolled over into this 52-week open-label study (amended to 26 weeks towards the end) from three randomized, double-blind, placebo-controlled Phase 3 studies...
February 3, 2018: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29343962/functioning-outcomes-with-adjunctive-treatments-for-major-depressive-disorder-a-systematic-review-of-randomized-placebo-controlled-studies
#10
REVIEW
Emmanuelle Weiller, Catherine Weiss, Christopher P Watling, Christopher Edge, Mary Hobart, Hans Eriksson, Maurizio Fava
Objective: Patients with major depressive disorder (MDD) with inadequate response to antidepressant treatment (ADT) may suffer a prolonged loss of functioning. This review aimed to determine if self-rated functional measures are informative in randomized placebo-controlled studies of adjunctive therapy in patients with MDD and inadequate response to ADT. Methods: This was a systematic literature review of articles in any language from the MEDLINE database published between January 1990 and March 2017...
2018: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/29343128/efficacy-and-safety-of-flexibly-dosed-brexpiprazole-for-the-adjunctive-treatment-of-major-depressive-disorder-a-randomized-active-referenced-placebo-controlled-study
#11
Mary Hobart, Aleksandar Skuban, Peter Zhang, Mette Krog Josiassen, Nanco Hefting, Carole Augustine, Claudette Brewer, Raymond Sanchez, Robert D McQuade
OBJECTIVE: To assess the efficacy, safety, and tolerability of brexpiprazole as adjunctive treatment in adults with major depressive disorder (MDD) and an inadequate response to prior antidepressant treatment (ADT). METHODS: Patients with a current major depressive episode after prior treatment with 1-3 ADTs entered an 8- or 10-week prospective treatment phase in which they received double-blind placebo adjunct to open-label ADT. Inadequate responders were randomized (2:2:1) to brexpiprazole 2-3 mg/day, placebo, or quetiapine extended-release (XR) 150-300 mg/day, adjunct to the same ADT, for 6 weeks...
April 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29224968/adjunctive-treatment-with-brexpiprazole-and-escitalopram-reduces-behavioral-stress-responses-and-increase-hypothalamic-npy-immunoreactivity-in-a-rat-model-of-ptsd-like-symptoms
#12
Hagit Cohen, Joseph Zohar, Zeev Kaplan, Jørn Arnt
The study explored effects of brexpiprazole (partial D2 /5-HT1A agonist, 5-HT2A and α1B/2C -adrenoceptor antagonist) in rats exposed to predator scent stress (PSS), a proposed model of PTSD-like phenotype. Brexpiprazole (3.0mg/kg, PO), escitalopram (5.0mg/kg, IP) and their combination were administered twice daily for 14 days, starting 14 days after exposure to PSS or sham-PSS, shortly after a situational stress reminder. One day after last treatment behavioral responsivity was assessed. Brexpiprazole+escitalopram-treated rats spent more time in open arms, entered open arms more often and exhibited a lower anxiety index in the elevated plus maze than vehicle-treated, PSS-exposed rats...
January 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29152847/a-case-study-in-identifying-targeted-patients-population-in-major-depressive-disorder-by-enhanced-enrichment-design
#13
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
#14
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...
December 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29109605/brexpiprazole-for-schizophrenia
#15
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
#16
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)...
February 2018: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29017334/brexpiprazole-a-new-leaf-on-the-partial-dopamine-agonist-branch
#17
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...
February 2018: 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
#18
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...
January 31, 2018: 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
#19
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...
January 2018: 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
#20
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
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