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      EPA guidance on assessment of negative symptoms in schizophrenia

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          Abstract

          Background

          During the last decades, a renewed interest for negative symptoms (NS) was brought about by the increased awareness that they interfere severely with real-life functioning, particularly when they are primary and persistent.

          Methods

          In this guidance paper, we provide a systematic review of the evidence and elaborate several recommendations for the conceptualization and assessment of NS in clinical trials and practice.

          Results

          Expert consensus and systematic reviews have provided guidance for the optimal assessment of primary and persistent negative symptoms; second-generation rating scales, which provide a better assessment of the experiential domains, are available; however, NS are still poorly assessed both in research and clinical settings.

          This European Psychiatric Association (EPA) guidance recommends the use of persistent negative symptoms (PNS) construct in the context of clinical trials and highlights the need for further efforts to make the definition of PNS consistent across studies in order to exclude as much as possible secondary negative symptoms. We also encourage clinicians to use second-generation scales, at least to complement first-generation ones.

          The EPA guidance further recommends the evidence-based exclusion of several items included in first-generation scales from any NS summary or factor score to improve NS measurement in research and clinical settings. Self-rated instruments are suggested to further complement observer-rated scales in NS assessment.

          Several recommendations are provided for the identification of secondary negative symptoms in clinical settings.

          Conclusions

          The dissemination of this guidance paper may promote the development of national guidelines on negative symptom assessment and ultimately improve the care of people with schizophrenia.

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          Most cited references238

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          The positive and negative syndrome scale (PANSS) for schizophrenia.

          The variable results of positive-negative research with schizophrenics underscore the importance of well-characterized, standardized measurement techniques. We report on the development and initial standardization of the Positive and Negative Syndrome Scale (PANSS) for typological and dimensional assessment. Based on two established psychiatric rating systems, the 30-item PANSS was conceived as an operationalized, drug-sensitive instrument that provides balanced representation of positive and negative symptoms and gauges their relationship to one another and to global psychopathology. It thus constitutes four scales measuring positive and negative syndromes, their differential, and general severity of illness. Study of 101 schizophrenics found the four scales to be normally distributed and supported their reliability and stability. Positive and negative scores were inversely correlated once their common association with general psychopathology was extracted, suggesting that they represent mutually exclusive constructs. Review of five studies involving the PANSS provided evidence of its criterion-related validity with antecedent, genealogical, and concurrent measures, its predictive validity, its drug sensitivity, and its utility for both typological and dimensional assessment.
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            Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.

            The relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents are currently used far more commonly. We compared a first-generation antipsychotic, perphenazine, with several newer drugs in a double-blind study. A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and randomly assigned to receive olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the Food and Drug Administration. The primary aim was to delineate differences in the overall effectiveness of these five treatments. Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P<0.001) or risperidone (P=0.002) group, but not in the perphenazine (P=0.021) or ziprasidone (P=0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P=0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and perphenazine was associated with more discontinuation for extrapyramidal effects. The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons. Olanzapine was the most effective in terms of the rates of discontinuation, and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism. Copyright 2005 Massachusetts Medical Society.
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              Psychiatric comorbidities and schizophrenia.

              Psychiatric comorbidities are common among patients with schizophrenia. Substance abuse comorbidity predominates. Anxiety and depressive symptoms are also very common throughout the course of illness, with an estimated prevalence of 15% for panic disorder, 29% for posttraumatic stress disorder, and 23% for obsessive-compulsive disorder. It is estimated that comorbid depression occurs in 50% of patients, and perhaps (conservatively) 47% of patients also have a lifetime diagnosis of comorbid substance abuse. This article chronicles these associations, examining whether these comorbidities are "more than chance" and might represent (distinct) phenotypes of schizophrenia. Among the anxiety disorders, the evidence at present is most abundant for an association with obsessive-compulsive disorder. Additional studies in newly diagnosed antipsychotic-naive patients and their first-degree relatives and searches for genetic and environmental risk factors are needed to replicate preliminary findings and further investigate these associations.
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                Author and article information

                Journal
                Eur Psychiatry
                Eur Psychiatry
                EPA
                European Psychiatry
                Cambridge University Press (Cambridge, UK )
                0924-9338
                1778-3585
                2021
                08 February 2021
                : 64
                : 1
                : e23
                Affiliations
                [1 ]Department of Psychiatry, Campania University Luigi Vanvitelli , Naples, Italy
                [2 ]CHU de Caen, Service de Psychiatrie , 14000 Caen, France
                [3 ]Normandie Univ, UNICAEN , ISTS EA 7466, GIP Cyceron, 14000 Caen, France
                [4 ]Normandie Univ, UNICAEN , UFR de Médecine, 14000 Caen, France
                [5 ]Copenhagen Research Centre for Mental Health (CORE), Copenhagen University Hospital , Copenhagen, Denmark
                [6 ]Department of Clinical Medicine, Faculty of Health and Medical Science, University of Copenhagen , Copenhagen, Denmark
                [7 ]Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS , Glostrup, Denmark
                [8 ]Department of Psychiatry, University of Munich , Munich, Germany
                [9 ]Division of Adult Psychiatry, Department of Psychiatry, Geneva University Hospitals , Geneva, Switzerland
                [10 ]Center for Neuropsychiatric Schizophrenia Research, CNSR , Glostrup, Denmark
                [11 ]Department of Psychiatry and Psychotherapy, Semmelweis University , Budapest, Hungary
                [12 ]Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University , Düsseldorf, Germany
                Author notes
                [* ] Address for correspondence: Armida Mucci, E-mail: armida.mucci@ 123456gmail.com
                Author information
                https://orcid.org/0000-0002-1592-7656
                https://orcid.org/0000-0002-6195-9456
                https://orcid.org/0000-0002-3013-2034
                https://orcid.org/0000-0003-3621-8450
                https://orcid.org/0000-0002-8530-5596
                Article
                S0924933821000110
                10.1192/j.eurpsy.2021.11
                8080207
                33597064
                b92fff3e-216c-4eca-ab03-4016c77f1438
                © The Author(s), 2021. Published by Cambridge University Press on behalf of the European Psychiatric Association 2021

                This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 December 2020
                : 08 February 2021
                : 09 February 2021
                Page count
                Figures: 2, Tables: 18, References: 239, Pages: 23
                Categories
                EPA Guidance

                Clinical Psychology & Psychiatry
                assessment instruments,conceptualization,persistent negative symptoms,primary negative symptoms,secondary negative symptoms

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