4
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Spotlight on brexpiprazole and its potential in the treatment of schizophrenia and as adjunctive therapy for the treatment of major depression

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Antipsychotic agents, utilized for the treatment of a range of psychiatric disorders, differ substantially in terms of their pharmacology and adverse effect profiles. Incomplete and variable efficacy, differences in safety–tolerability, and highly heterogeneous response across individuals prompt development of new agents. Brexpiprazole is one of the two most recently introduced antipsychotic agents approved for the treatment of schizophrenia and as an adjunct for treatment of major depressive disorder. Its pharmacology, clinical trial data, and efficacy and side effects in comparison with other antipsychotic agents are discussed. Brexpiprazole is a dopamine D-2 partial agonist with potent activity at the serotonin 5HT 1A and 5HT 2A and noradrenergic alpha-1B and alpha-2C receptors. Placebo-controlled clinical trials in persons with schizophrenia support its efficacy in treating psychosis and preventing relapse. Short-term clinical trials also support its efficacy as an adjunct to antidepressants in treating major depressive disorder in individuals inadequately responsive to antidepressant treatment alone. Adverse effects include akathisia, gastrointestinal side effects, and moderate weight gain. The recommended oral dose of brexpiprazole is 2–4 mg/day in schizophrenia and 2–3 mg/day as adjunctive treatment in major depression. It must be titrated up to its target dose over 1–2 weeks and is effective in once-daily dosing. How brexpiprazole’s unique pharmacological profile will translate into clinically meaningful differences from other antipsychotic agents is unclear. Its place in our antipsychotic armamentarium and potential role in the treatment of schizophrenia and major depressive disorder will be determined by additional clinical data and experience.

          Related collections

          Most cited references 27

          • Record: found
          • Abstract: found
          • Article: not found

          Schizophrenia, "just the facts" 5. Treatment and prevention. Past, present, and future.

          The introduction of second-generation antipsychotics and cognitive therapies for schizophrenia over the past two decades generated considerable optimism about possibilities for recovery. To what extent have these developments resulted in better outcomes for affected individuals? What is the current state of our science and how might we address the many unmet needs in the prevention and treatment of schizophrenia? We trace the evolution of various treatments for schizophrenia and summarize current knowledge about available pharmacological and psychosocial treatments. We consider the widely prevalent efficacy-effectiveness gap in the application of available treatments and note the significant variability in individual treatment response and outcome. We outline an individualized treatment approach which emphasizes careful monitoring and collaborative decision-making in the context of ongoing benefit-risk assessment. We note that the evolution of both pharmacological and psychosocial treatments thus far has been based principally on serendipity and intuition. In view of our improved understanding of the etiology and pathophysiology of schizophrenia, there is an opportunity to develop prevention strategies and treatments based on this enhanced knowledge. In this context, we discuss potential psychopathological treatment targets and enumerate current pharmacological and psychosocial development efforts directed at them. Considering the stages of schizophrenic illness, we review approaches to prevent progression from the pre-symptomatic high-risk to the prodrome to the initial psychotic phase to chronicity. In view of the heterogeneity of risk factors, we summarize approaches towards targeted prevention. We evaluate the potential contribution of pharmacogenomics and other biological markers in optimizing individual treatment and outcome in the future. (c) 2010 Elsevier B.V. All rights reserved.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a second multicenter, randomized, double-blind, placebo-controlled study.

            Nonresponse to one or more antidepressants is common and an important public health problem. This study evaluated the efficacy and safety of adjunctive aripiprazole or placebo to standard antidepressant therapy (ADT) in patients with major depressive disorder who showed an inadequate response to at least 1 and up to 3 historical and 1 additional prospective ADT. The study comprised a 7-28-day screening, an 8-week prospective treatment, and a 6-week randomization phase. During prospective treatment, patients experiencing a major depressive episode (17-item Hamilton Rating Scale for Depression total score > or = 18) received single-blind adjunctive placebo plus clinicians' choice of ADT (escitalopram, fluoxetine, paroxetine controlled-release, sertraline, or venlafaxine extended-release). Subjects with inadequate response were randomized to adjunctive placebo (n = 190) or adjunctive aripiprazole (n = 191) (starting dose 5 mg/d, dose adjustments 2-20 mg/d, mean end-point dose of 11.0 mg/d). The primary efficacy endpoint was the mean change in Montgomery-Asberg Depression Rating Scale total score from end of prospective treatment phase to end of randomized treatment phase (last observation carried forward). Mean change in Montgomery-Asberg Depression Rating Scale total score was significantly greater with adjunctive aripiprazole than placebo (-8.5 vs -5.7; P = 0.001). Remission rates were significantly greater with adjunctive aripiprazole than placebo (25.4% vs 15.2%; P = 0.016) as were response rates (32.4% vs 17.4%; P < 0.001). Adverse events occurring in 10% of patients or more with adjunctive placebo or aripiprazole were akathisia (4.2% vs 25.9%), headache (10.5% vs 9.0%), and fatigue (3.7% vs 10.1%). Incidence of adverse events leading to discontinuation was low (adjunctive placebo [1.1%] vs adjunctive aripiprazole [3.7%]). Aripiprazole is an effective and safe adjunctive therapy as demonstrated in this short-term study for patients who are nonresponsive to standard ADT.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Brexpiprazole I: in vitro and in vivo characterization of a novel serotonin-dopamine activity modulator.

              Brexpiprazole (OPC-34712, 7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}quinolin-2(1H)-one) is a novel drug candidate in clinical development for psychiatric disorders with high affinity for serotonin, dopamine, and noradrenaline receptors. In particular, it bound with high affinity (Ki 1000 nM). Brexpiprazole potently bound to rat 5-HT2A and D2 receptors in vivo, and ex vivo binding studies further confirmed high 5-HT1A receptor binding potency. Brexpiprazole inhibited DOI (2,5-dimethoxy-4-iodoamphetamine)-induced head twitches in rats, suggestive of 5-HT2A antagonism. Furthermore, in vivo D2 partial agonist activity of brexpiprazole was confirmed by its inhibitory effect on reserpine-induced DOPA accumulation in rats. In rat microdialysis studies, brexpiprazole slightly reduced extracellular dopamine in nucleus accumbens but not in prefrontal cortex, whereas moderate increases of the dopamine metabolites, homovanillic acid and DOPAC (3,4-dihydroxy-phenyl-acetic acid), in these areas also suggested in vivo D2 partial agonist activity. In particular, based on a lower intrinsic activity at D2 receptors and higher binding affinities for 5-HT1A/2A receptors than aripiprazole, brexpiprazole would have a favorable antipsychotic potential without D2 receptor agonist- and antagonist-related adverse effects. In conclusion, brexpiprazole is a serotonin-dopamine activity modulator with a unique pharmacology, which may offer novel treatment options across a broad spectrum of central nervous system disorders.
                Bookmark

                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2016
                11 May 2016
                : 10
                : 1641-1647
                Affiliations
                Department of Psychiatry, University of Florida College of Medicine, Gainesville, FL, USA
                Author notes
                Correspondence: Dawn Bruijnzeel, Department of Psychiatry, University of Florida College of Medicine, 1601 SW Archer Rd, 116A, Gainesville, FL 32608, USA, Tel +1 352 376 1611 ext 4381, Email dheron@ 123456ufl.edu
                Article
                dddt-10-1641
                10.2147/DDDT.S85089
                4869657
                27274197
                © 2016 Bruijnzeel and Tandon. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Review

                Comments

                Comment on this article