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      Factors associated with first- versus second-generation long-acting antipsychotics prescribed under ordinary clinical practice in Italy

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          Abstract

          Background

          For many years, long-acting intramuscular (LAI) antipsychotics have been prescribed predominantly to chronic and severe patients, as a last resort when other treatments failed. Recently, a broader and earlier use of LAIs, particularly second-generation LAIs, has been emphasized. To date, few studies attempted to frame how this change in prescribing took place in real-world practice. Therefore, this study aimed to describe the clinical features of patients prescribed with LAIs, and to explore possible prescribing differences between first- and second-generations LAIs under ordinary clinical practice in Italy.

          Methods

          The STAR Network “Depot” Study is an observational, longitudinal, multicenter study involving 35 centers in Italy. In the cross-sectional phase, patients prescribed with LAIs were consecutively recruited and assessed over a period of 12 months. Descriptive statistics and multivariable logistic regression analyses were employed.

          Results

          Of the 451 recruited patients, 61% were males. The level of social and working functioning was heterogeneous, as was the severity of disease. Seventy-two per cent of the patients had a diagnosis of the schizophrenia spectrum. Seventy per cent were prescribed with second-generation antipsychotic (SGA) LAIs (mostly paliperidone, aripiprazole and risperidone). Compared to first-generation antipsychotic (FGA) LAIs, patients prescribed with SGA LAIs were more often younger; employed; with a diagnosis of the schizophrenia spectrum or bipolar disorder; with higher levels of affective symptoms; with fewer LAI prescriptions in the past.

          Discussion

          LAIs’ prescribing practices appear to be more flexible as compared to the past, although this change is mostly restricted to SGA LAIs.

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          Most cited references69

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          Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study.

          The prevalence of comorbid alcohol, other drug, and mental disorders in the US total community and institutional population was determined from 20,291 persons interviewed in the National Institute of Mental Health Epidemiologic Catchment Area Program. Estimated US population lifetime prevalence rates were 22.5% for any non-substance abuse mental disorder, 13.5% for alcohol dependence-abuse, and 6.1% for other drug dependence-abuse. Among those with a mental disorder, the odds ratio of having some addictive disorder was 2.7, with a lifetime prevalence of about 29% (including an overlapping 22% with an alcohol and 15% with another drug disorder). For those with either an alcohol or other drug disorder, the odds of having the other addictive disorder were seven times greater than in the rest of the population. Among those with an alcohol disorder, 37% had a comorbid mental disorder. The highest mental-addictive disorder comorbidity rate was found for those with drug (other than alcohol) disorders, among whom more than half (53%) were found to have a mental disorder with an odds ratio of 4.5. Individuals treated in specialty mental health and addictive disorder clinical settings have significantly higher odds of having comorbid disorders. Among the institutional settings, comorbidity of addictive and severe mental disorders was highest in the prison population, most notably with antisocial personality, schizophrenia, and bipolar disorders.
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            Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29 823 Patients With Schizophrenia

            Importance It has remained unclear whether there are clinically meaningful differences between antipsychotic treatments with regard to preventing relapse of schizophrenia, owing to the impossibility of including large unselected patient populations in randomized clinical trials, as well as residual confounding from selection biases in observational studies. Objective To study the comparative real-world effectiveness of antipsychotic treatments for patients with schizophrenia. Design, Setting, and Participants Prospectively gathered nationwide databases were linked to study the risk of rehospitalization and treatment failure from July 1, 2006, to December 31, 2013, among all patients in Sweden with a schizophrenia diagnosis who were 16 to 64 years of age in 2006 (29 823 patients in the total prevalent cohort; 4603 in the incident cohort of newly diagnosed patients). Within-individual analyses were used for primary analyses, in which each individual was used as his or her own control to eliminate selection bias. Traditional Cox proportional hazards multivariate regression was used for secondary analyses. Main Outcomes and Measures Risk of rehospitalization and treatment failure (defined as psychiatric rehospitalization, suicide attempt, discontinuation or switch to other medication, or death). Results There were 29 823 patients (12 822 women and 17 001 men; mean [SD] age, 44.9 [12.0] years). During follow-up, 13 042 of 29 823 patients (43.7%) were rehospitalized, and 20 225 of 28 189 patients (71.7%) experienced treatment failure. The risk of psychiatric rehospitalization was the lowest during monotherapy with once-monthly long-acting injectable paliperidone (hazard ratio [HR], 0.51; 95% CI, 0.41-0.64), long-acting injectable zuclopenthixol (HR, 0.53; 95% CI, 0.48-0.57), clozapine (HR, 0.53; 95% CI, 0.48-0.58), long-acting injectable perphenazine (HR, 0.58; 95% CI, 0.52-0.65), and long-acting injectable olanzapine (HR, 0.58; 95% CI, 0.44-0.77) compared with no use of antipsychotic medication. Oral flupentixol (HR, 0.92; 95% CI, 0.74-1.14), quetiapine (HR, 0.91; 95% CI, 0.83-1.00), and oral perphenazine (HR, 0.86; 95% CI, 0.77-0.97) were associated with the highest risk of rehospitalization. Long-acting injectable antipsychotic medications were associated with substantially lower risk of rehospitalization compared with equivalent oral formulations (HR, 0.78; 95% CI, 0.72-0.84 in the total cohort; HR, 0.68; 95% CI, 0.53-0.86 in the incident cohort). Clozapine (HR, 0.58; 95% CI, 0.53-0.63) and all long-acting injectable antipsychotic medications (HRs 0.65-0.80) were associated with the lowest rates of treatment failure compared with the most widely used medication, oral olanzapine. The results of several sensitivity analyses were consistent with those of the primary analyses. Conclusions and Relevance Clozapine and long-acting injectable antipsychotic medications were the pharmacologic treatments with the highest rates of prevention of relapse in schizophrenia. The risk of rehospitalization is about 20% to 30% lower during long-acting injectable treatments compared with equivalent oral formulations. This database study uses a nationwide cohort to examine the comparative real-world effectiveness of antipsychotic treatments for patients with schizophrenia. Question Are there any clinically meaningful differences between specific antipsychotic medications or routes of administration regarding the risk of psychiatric rehospitalization or other treatment failure? Findings This database study of a nationwide cohort of patients using within-individual analysis to eliminate selection bias found that clozapine and long-acting injections of antipsychotic medications are associated with the lowest risk of rehospitalization and treatment failure. Meaning Clozapine and long-acting injections of antipsychotic medications were the pharmacologic treatments with the highest rates of prevention of relapse in schizophrenia.
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              Clinical implications of Brief Psychiatric Rating Scale scores.

              Despite the widespread use of the Brief Psychiatric Rating Scale (BPRS), the clinical meaning of its total score and cut-off values used to define treatment response are unclear. To link the BPRS to Clinical Global Impression (CGI) ratings. Equipercentile linking of BPRS and CGI ratings from seven drug trials in acutely ill patients with schizophrenia (n=1979). 'Mildly ill' according to the CGI approximately corresponded to a BPRS total score of 31, 'moderately ill'to a BPRS score of 41 and'markedly ill'to a BPRS score of 53.'Minimally improved'according to the CGI score was associated with percentage BPRS reductions of 24, 27 and 30% at weeks 1, 2 and 4, respectively. The corresponding numbers for a CGI rating of 'much improved' were 44, 53 and 58%. The results provide a clearer understanding of how to interpret BPRS total and percentage reduction scores in clinical trials with patients acutely ill with schizophrenia who are experiencing positive symptoms.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Methodology
                Role: Data curationRole: InvestigationRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                2 August 2018
                2018
                : 13
                : 8
                : e0201371
                Affiliations
                [1 ] WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy
                [2 ] Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, IRCCS "Policlinico San Martino" Hospital, University of Genoa, Genoa, Italy
                [3 ] "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy
                [4 ] Department of Medicine and Surgery, University of Milano Bicocca, Monza, Italy
                [5 ] Università degli Studi dell'Insubria, Dipartimento di Salute Mentale e Dipendenze-ASST Settelaghi Varese, Varese, Italy
                [6 ] Department of Health Sciences, Psychiatric Unit, University Magna Græcia of Catanzaro, Catanzaro, Italy
                [7 ] Division of Psychiatry, University College of London, London, UK
                [8 ] Department of Neuroscience, Imaging and Clinical Sciences, University "G. d'Annunzio", Chieti, Italy
                [9 ] Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
                [10 ] Department of Mental Health, San Paolo Hospital, Milan, Italy
                [11 ] Mental Health Department, USL Toscana sudest-Siena, Siena, Italy
                Universita Cattolica del Sacro Cuore Sede di Roma, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                ¶ Membership of the STAR Network is provided in the Acknowledgments.

                Author information
                http://orcid.org/0000-0003-2248-9524
                http://orcid.org/0000-0003-0936-2908
                http://orcid.org/0000-0002-0624-9988
                http://orcid.org/0000-0002-2126-799X
                http://orcid.org/0000-0002-8717-0832
                http://orcid.org/0000-0001-6482-8593
                Article
                PONE-D-18-14220
                10.1371/journal.pone.0201371
                6072022
                30071042
                7e2a2d3a-7b73-484d-b608-53f315e2a9f6
                © 2018 Ostuzzi et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 11 May 2018
                : 13 July 2018
                Page count
                Figures: 1, Tables: 3, Pages: 17
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Antipsychotics
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Schizophrenia
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Mood Disorders
                Bipolar Disorder
                People and places
                Geographical locations
                Europe
                European Union
                Italy
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Multivariate Analysis
                Bivariate Analysis
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Multivariate Analysis
                Bivariate Analysis
                People and Places
                Population Groupings
                Ethnicities
                European People
                Italian People
                Social Sciences
                Economics
                Labor Economics
                Employment
                Medicine and Health Sciences
                Epidemiology
                Custom metadata
                The full dataset is available from the Dryad Digital Repository, doi: 10.5061/dryad.q49p6d8.

                Uncategorized
                Uncategorized

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