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      Clinical potential of lurasidone in the management of schizophrenia

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          Abstract

          Lurasidone is a new second-generation antipsychotic approved in October 2010 by the Food and Drug Administration for the treatment of schizophrenia. Like other second-generation antipsychotics, lurasidone is a powerful antagonist of D 2 dopamine and 5HT 2A serotonin receptors, but differs from the other second-generation antipsychotics in its action profile for certain receptors. Lurasidone is the second-generation antipsychotic with the greatest affinity for 5HT 7 receptors and has a high affinity for 5HT 1A serotonin receptors, compatible with favorable effects on cognitive function and an antidepressant action. By contrast, lurasidone has a low affinity for and α 1 α 2C-adrenergic and 5HT 2C serotonin receptors, and no affinity for histaminergic H 1 or muscarinic M 1 receptors, suggesting a better tolerability profile than the other second-generation antipsychotics. Lurasidone has demonstrated its efficacy in several short-term trials in acute schizophrenia, promptly and significantly reducing total Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale scores compared with placebo. Several long-term studies are in progress to assess its efficacy in the maintenance treatment of schizophrenic patients. The efficacy of lurasidone with regard to cognitive functions and depressive symptoms seems good, but requires further work. Lurasidone differs from the other second-generation antipsychotics by having a good tolerability profile, in particular for cardiometabolic tolerability. However, it seems to have a significant although moderate link with the occurrence of akathisia, extrapyramidal symptoms, and hyperprolactinemia at the start of treatment. This tolerance profile greatly broadens the scope of second-generation antipsychotics and so supports the view of some authors that the term “second-generation antipsychotic” is now outdated. Other therapeutic perspectives of lurasidone are assessed here, in particular bipolar depression.

          Most cited references32

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          The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements.

          In light of the large number of studies published since the 2004 update of Schizophrenia Patient Outcomes Research Team psychopharmacological treatment recommendations, we conducted an extensive literature review to determine whether the current psychopharmacological treatment recommendations required revision and whether there was sufficient evidence to warrant new treatment recommendations for prespecified outcomes of interest. We reviewed over 400 articles, which resulted in 16 treatment recommendations: the revision of 11 previous treatment recommendations and 5 new treatment recommendations. Three previous treatment recommendations were eliminated. There were 13 interventions and/or outcomes for which there was insufficient evidence for a treatment recommendation, and a statement was written to summarize the current level of evidence and identify important gaps in our knowledge that need to be addressed. In general, there was considerable consensus among the Psychopharmacology Evidence Review Group and the expert consultants. Two major areas of contention concerned whether there was sufficient evidence to recommend specific dosage ranges for the acute and maintenance treatment of first-episode and multi-episode schizophrenia and to endorse the practice of switching antipsychotics for the treatment of antipsychotic-related weight gain. Finally, there continue to be major gaps in our knowledge, including limited information on (1) the use of adjunctive pharmacological agents for the treatment of persistent positive symptoms or other symptom domains of psychopathology, including anxiety, cognitive impairments, depressive symptoms, and persistent negative symptoms and (2) the treatment of co-occurring substance or medical disorders that occur frequently in individuals with schizophrenia.
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            Randomized controlled trial of the effect on Quality of Life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1).

            Second-generation (atypical) antipsychotics (SGAs) are more expensive than first-generation (typical) antipsychotics (FGAs) but are perceived to be more effective, with fewer adverse effects, and preferable to patients. Most evidence comes from short-term efficacy trials of symptoms. To test the hypothesis that in people with schizophrenia requiring a change in treatment, SGAs other than clozapine are associated with improved quality of life across 1 year compared with FGAs. A noncommercially funded, pragmatic, multisite, randomized controlled trial of antipsychotic drug classes, with blind assessments at 12, 26, and 56 weeks using intention-to-treat analysis. Fourteen community psychiatric services in the English National Health Service. Two hundred twenty-seven people aged 18 to 65 years with DSM-IV schizophrenia and related disorders assessed for medication review because of inadequate response or adverse effects. Randomized prescription of either FGAs or SGAs (other than clozapine), with the choice of individual drug made by the managing psychiatrist. Quality of Life Scale scores, symptoms, adverse effects, participant satisfaction, and costs of care. The primary hypothesis of significant improvement in Quality of Life Scale scores during the year after commencement of SGAs vs FGAs was excluded. Participants in the FGA arm showed a trend toward greater improvements in Quality of Life Scale and symptom scores. Participants reported no clear preference for either drug group; costs were similar. In people with schizophrenia whose medication is changed for clinical reasons, there is no disadvantage across 1 year in terms of quality of life, symptoms, or associated costs of care in using FGAs rather than nonclozapine SGAs. Neither inadequate power nor patterns of drug discontinuation accounted for the result.
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              A meta-analysis of head-to-head comparisons of second-generation antipsychotics in the treatment of schizophrenia.

              Whether there are differences in efficacy among second-generation antipsychotics in the treatment of schizophrenia is a matter of heated debate. The authors conducted a systematic review and meta-analysis of blinded studies comparing second-generation antipsychotics head-to-head. Searches of the Cochrane Schizophrenia Group's register (May 2007) and MEDLINE (September 2007) were conducted for randomized, blinded studies comparing two or more of nine second-generation antipsychotics in the treatment of schizophrenia. All data were extracted by at least three reviewers independently. The primary outcome measure was change in total score on the Positive and Negative Syndrome Scale; secondary outcome measures were positive and negative symptom subscores and rate of dropout due to inefficacy. The results were combined in a meta-analysis. Various sensitivity analyses and metaregressions were used to examine bias. The analysis included 78 studies with 167 relevant arms and 13,558 participants. Olanzapine proved superior to aripiprazole, quetiapine, risperidone, and ziprasidone. Risperidone was more efficacious than quetiapine and ziprasidone. Clozapine proved superior to zotepine and, in doses >400 mg/day, to risperidone. These differences were due to improvement in positive symptoms rather than negative symptoms. The results were rather robust with regard to the effects of industry sponsorship, study quality, dosages, and trial duration. The findings suggest that some second-generation antipsychotics may be somewhat more efficacious than others, but the limitations of meta-analysis must be considered. In tailoring drug treatment to the individual patient, small efficacy superiorities must be weighed against large differences in side effects and cost.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2011
                2011
                27 June 2011
                : 7
                : 239-250
                Affiliations
                Centre Hospitalier Universitaire, Clermont-Ferrand, France
                Author notes
                Correspondence: L Samalin, Centre Médico-Psychologique B, Centre Hospitalier Universitaire, BP 69, 63003 Clermont-Ferrand, Cedex 1, France, Tel +33 04 7375 2125, Fax +33 04 7375 2126, Email lsamalin@ 123456chu-clermontferrand.fr
                Article
                tcrm-7-239
                10.2147/TCRM.S12701
                3132094
                21753886
                df979598-cc89-4942-b4ee-dcde025c3571
                © 2011 Samalin et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                History
                : 24 June 2011
                Categories
                Review

                Medicine
                lurasidone,second-generation antipsychotic,schizophrenia,efficacy,safety
                Medicine
                lurasidone, second-generation antipsychotic, schizophrenia, efficacy, safety

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