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      Iloperidone in the treatment of schizophrenia: an evidence-based review of its place in therapy

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          Abstract

          Introduction

          Schizophrenia is a chronic and debilitating mental disorder that affects the patient’s and their family’s quality of life, as well as financial costs and health care settings. Despite the variety of available antipsychotics, optimal treatment outcomes are not always achieved. Novel drugs, such as iloperidone, can provide more effective, tolerable and safer strategies.

          Aim

          To review the evidence for the clinical impact of iloperidone on the treatment of patients with schizophrenia.

          Evidence review

          Clinical trials, observational studies and meta-analyses reached a common consensus that iloperidone is as effective as haloperidol, risperidone and ziprasidone in reducing schizophrenia symptoms. Similar amounts of adverse events and discontinuations were observed with iloperidone compared to placebo and active treatments. Common adverse events are mild and include dizziness, hypotension, dry mouth and weight gain. Iloperidone can induce extension of QTc interval, and clinicians should be aware of its contraindications. In long-term trials, iloperidone also showed promising safety and tolerability profiles. The low propensity to cause akathisia, extrapyramidal symptoms (EPS), increased prolactin levels or changes to metabolic laboratory parameters support its use in practice. Results showed that iloperidone prevents relapse in stabilized patients, with a time to relapse superior to placebo and similar to haloperidol. Patients using a prior antipsychotic (eg, risperidone and aripiprazole) can easily switch to iloperidone with no serious impact on safety or efficacy. However, the acquisition costs of iloperidone may hamper its use. Further evidence comparing iloperidone with other antipsychotics, and pharmacoeconomic studies would be welcome.

          Place in therapy

          Considering just the clinical profile of iloperidone, it represents a promising drug for treating schizophrenia, particularly in patients who are intolerant to previous antipsychotics, as well as being suitable as first-line therapy. Cost-effectiveness comparisons are needed to justify its use in clinical practice.

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          Most cited references62

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          Meta-analysis of diffusion tensor imaging studies in schizophrenia.

          The objective of the study was to identify whether there are consistent regional white matter changes in schizophrenia. A systematic search was conducted for voxel-based diffusion tensor imaging fractional anisotropy studies of patients with schizophrenia (or related disorders) in relation to comparison groups. The authors carried out meta-analysis of the co-ordinates of fractional anisotropy differences. For the meta-analysis they used the Activation Likelihood Estimation (ALE) method hybridized with the rank approach used in Genome Scan Meta-Analysis (GSMA). This system detects three-dimensional conjunctions of co-ordinates from multiple studies and permits the weighting of studies in relation to sample size. Fifteen articles were identified for inclusion in the meta-analysis, including a total of 407 patients with schizophrenia and 383 comparison subjects. The studies reported fractional anisotropy reductions at 112 co-ordinates in schizophrenia and no fractional anisotropy increases. Over all studies, significant reductions were present in two regions: the left frontal deep white matter and the left temporal deep white matter. The first region, in the left frontal lobe, is traversed by white matter tracts interconnecting the frontal lobe, thalamus and cingulate gyrus. The second region, in the temporal lobe, is traversed by white matter tracts interconnecting the frontal lobe, insula, hippocampus-amygdala, temporal and occipital lobe. This suggests that two networks of white matter tracts may be affected in schizophrenia, with the potential for 'disconnection' of the gray matter regions which they link.
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            The Economic Burden of Schizophrenia in the United States in 2013.

            The objective of this study was to estimate the US societal economic burden of schizophrenia and update the 2002 reported costs of $62.7 billion given the disease management and health care structural changes of the last decade.
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              Are there progressive brain changes in schizophrenia? A meta-analysis of structural magnetic resonance imaging studies.

              It is well established that schizophrenia is associated with structural brain abnormalities, but whether these are static or progress over time remains controversial. A systematic review of longitudinal volumetric studies using region-of-interest structural magnetic resonance imaging in patients with schizophrenia and healthy control subjects. The percentage change in volume between scans for each brain region of interest was obtained, and data were combined using random effects meta-analysis. Twenty-seven studies were included in the meta-analysis, with 928 patients and 867 control subjects, and 32 different brain regions of interest. Subjects with schizophrenia showed significantly greater decreases over time in whole brain volume, whole brain gray matter, frontal gray and white matter, parietal white matter, and temporal white matter volume, as well as larger increases in lateral ventricular volume, than healthy control subjects. The time between baseline and follow-up magnetic resonance imaging scans ranged from 1 to 10 years. The differences between patients and control subjects in annualized percentage volume change were -.07% for whole brain volume, -.59% for whole brain gray matter, -.32% for frontal white matter, -.32% for parietal white matter, -.39% for temporal white matter, and +.36% for bilateral lateral ventricles. These findings suggest that schizophrenia is associated with progressive structural brain abnormalities, affecting both gray and white matter. We found no evidence to suggest progressive medial temporal lobe involvement but did find evidence that this may be partly explained by heterogeneity between studies in patient age and illness duration. The causes and clinical correlates of these progressive brain changes should now be the focus of investigation. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Core Evid
                Core Evid
                Core Evidence
                Core Evidence
                Dove Medical Press
                1555-1741
                1555-175X
                2016
                14 December 2016
                : 11
                : 49-61
                Affiliations
                [1 ]Pharmaceutical Sciences Postgraduate Program
                [2 ]Department of Pharmacy, Federal University of Parana, Curitiba, Brazil
                [3 ]Department of Social Pharmacy, Faculty of Pharmacy, Research Institute for Medicines (iMed.ULisboa), Universidade de Lisboa, Lisbon, Portugal
                Author notes
                Correspondence: Roberto Pontarolo, Department of Pharmacy, Pharmaceutical Sciences Postgraduate Program, Federal University of Parana, Av. Prof. Lothario Meissner 632, Curitiba 80210-170, Brazil, Tel +55 41 3360 4094, Email pontarolo@ 123456ufpr.br
                Article
                ce-11-049
                10.2147/CE.S114094
                5167526
                28008301
                6bf46f5c-15f1-4311-ae63-1537a6b7a812
                © 2016 Tonin et al. 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.

                History
                Categories
                Review

                Pharmacology & Pharmaceutical medicine
                iloperidone,schizophrenia,clinical practice,evidence-based

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