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      Antipsychotic Polypharmacy in Treatment of Schizophrenia; Should or Should Not?

      review-article
      1 , 2 ,
      Chonnam Medical Journal
      Chonnam National University Medical School
      Antipsychotic Agents, Polypharmacy, Schizophrenia, Cohort Studies

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          Abstract

          Antipsychotics have been utilized as the standard treatment for schizophrenia regardless of illness phase where antipsychotic monotherapy (APM) is routinely recommended as the gold standard rather than antipsychotic polypharmacy (APP). However, approximately 20 to 40% of patients with schizophrenia do not respond to APM based on randomized controlled clinical trials and large practical clinical trials indicating that the subgroup of patients with schizophrenia would need differential treatment approaches beyond traditional treatment strategies such as APM. Numerous studies have supported the use of APP in particular for patients with certain clinical situations including: failure to show efficacy or tolerability from treatment with APM, need for different treatment for targeting specific symptom domains, severe illness, failure to treatment with clozapine, skepticism about following treatment guidelines, or cross titration periods. Furthermore, recent large cohort studies and practical clinical trials have proposed more benefits of APP rather than APM in terms of rehospitalization, mortality, and specific symptoms. APP has recently become more widely utilized and recognized as one of the next treatment strategies to clinicians for patients with schizophrenia. Some experts have already proposed the revision of treatment guidelines incorporating APP as evidence-based treatment option for certain patients with schizophrenia. Taken together, APP now deserves an evidence-based and acceptable treatment strategy, not an empirical or preferential treatment approach for treatment of schizophrenia in contemporary clinical practice.

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          Most cited references59

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          Clozapine Response Rates among People with Treatment-Resistant Schizophrenia: Data from a Systematic Review and Meta-Analysis

          Clozapine is the most effective antipsychotic for the 25% to 33% of people with schizophrenia who are treatment resistant, but not all people achieve response. Using data from a previously published clozapine systematic review and meta-analysis, we explored the proportion of people who achieved response and examined the absolute and percentage change in Positive and Negative Syndrome Scale (PANSS) scores. Overall, 40.1% (95% confidence interval [CI], 36.8%-43.4%) responded, with a mean reduction in PANSS of 22.0 points (95% CI, 20.9-23.1), a reduction of 25.8% (95% CI, 24.7%-26.9%) from baseline. These reductions are clinically meaningful. A 40% response rate to clozapine suggests that 12% to 20% of people with schizophrenia will be ultra-resistant. La clozapine est l’antipsychotique le plus efficace pour les 25 à 33% des personnes souffrant de schizophrénie qui sont réfractaires au traitement; toutefois, les personnes n’obtiennent pas toutes une réponse. À l’aide des données d’une revue systématique et d’une méta-analyse publiées précédemment, nous avons exploré la proportion de gens qui obtenaient une réponse, et examiné le pourcentage absolu et les changements de pourcentage dans les scores à l’échelle des syndromes positifs et négatifs (PANSS). Globalement, 40,1% (IC à 95% 36,8% à 43,4%) ont répondu, avec une réduction moyenne à la PANSS de 22,0 points (IC à 95% 20,9 à 23,1), une réduction de 25,8% (IC à 95% 24,7% à 26,9%) par rapport au départ. Ces réductions sont cliniquement significatives. Un taux de réponse de 40% à la clozapine suggère que de 12% à 20% des personnes souffrant de schizophrénie seront ultra-réfractaires.
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            Prevalence and correlates of antipsychotic polypharmacy: a systematic review and meta-regression of global and regional trends from the 1970s to 2009.

            To assess the prevalence and correlates of antipsychotic polypharmacy (APP) across decades and regions. Electronic PubMed/Google Scholar search for studies reporting on APP, published from 1970 to 05/2009. Median rates and interquartile ranges (IQR) were calculated and compared using non-parametric tests. Demographic and clinical variables were tested as correlates of APP in bivariate and meta-regression analyses. Across 147 studies (1,418,163 participants, 82.9% diagnosed with schizophrenia [IQR=42-100%]), the median APP rate was 19.6% (IQR=12.9-35.0%). Most common combinations included first-generation antipsychotics (FGAs)+second-generation antipsychotics (SGAs) (42.4%, IQR=0.0-71.4%) followed by FGAs+FGAs (19.6%, IQR=0.0-100%) and SGAs+SGAs (1.8%, IQR=0.0-28%). APP rates were not different between decades (1970-1979:28.8%, IQR=7.5-44%; 1980-1989:17.6%, IQR=10.8-38.2; 1990-1999:22.0%, IQR=11-40; 2000-2009:19.2% IQR=14.4-29.9, p=0.78), but between regions, being higher in Asia and Europe than North America, and in Asia than Oceania (p<0.001). APP increased numerically by 34% in North America from the 1980s 12.7%) to 2000s (17.0%) (p=0.94) and decreased significantly by 65% from 1980 (55.5%) to 2000 (19.2%) in Asia (p=0.03), with non-significant changes in Europe. APP was associated with inpatient status (p<0.001), use of FGAs (p<0.0001) and anticholinergics (<0.001), schizophrenia (p=0.01), less antidepressant use (p=0.02), greater LAIs use (p=0.04), shorter follow-up (p=0.001) and cross-sectional vs. longitudinal study design (p=0.03). In a meta-regression, inpatient status (p<0.0001), FGA use (0.046), and schizophrenia diagnosis (p=0.004) independently predicted APP (N=66, R(2)=0.44, p<0.0001). APP is common with different rates and time trends by region over the last four decades. APP is associated with greater anticholinergic requirement, shorter observation time, greater illness severity and lower antidepressant use. Copyright © 2012 Elsevier B.V. All rights reserved.
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              Association of Antipsychotic Polypharmacy vs Monotherapy With Psychiatric Rehospitalization Among Adults With Schizophrenia

              Key Points Question Are there specific antipsychotic combinations that are superior to monotherapies in the maintenance treatment of schizophrenia? Findings This cohort study on 62 250 individuals with schizophrenia with up to 20-year follow-up used within-individual analysis to minimize selection bias and showed that antipsychotic polypharmacy in general was associated with slightly lower risk of psychiatric rehospitalization than monotherapy. Clozapine plus aripiprazole combination was associated with the best outcome, having 14% to 23% lower risk of rehospitalization than clozapine alone, which was the monotherapy associated with the best outcomes. Meaning The findings of this study suggest that certain types of polypharmacy may be associated with fewer rehospitalizations than monotherapies.

                Author and article information

                Journal
                Chonnam Med J
                Chonnam Med J
                CMJ
                Chonnam Medical Journal
                Chonnam National University Medical School
                2233-7385
                2233-7393
                September 2020
                24 September 2020
                : 56
                : 3
                : 157-165
                Affiliations
                [1 ]Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Korea.
                [2 ]Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.
                Author notes
                Corresponding Author: Chi-Un Pae. Department of Psychiatry, Bucheon St. Mary's Hospital, The Catholic University of Korea College of Medicine, 327 Sosa-ro, Wonmi-gu, Bucheon 14647, Korea. Tel: +82-32-340-7067, Fax: +82-32-340-2255, pae@ 123456catholic.ac.kr
                Article
                10.4068/cmj.2020.56.3.157
                7520369
                33014754
                978257d6-9478-4af4-b61a-80ecdd23b5ed
                © Chonnam Medical Journal, 2020

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

                History
                : 02 August 2020
                : 19 August 2020
                : 19 August 2020
                Categories
                Review Article

                Medicine
                antipsychotic agents,polypharmacy,schizophrenia,cohort studies
                Medicine
                antipsychotic agents, polypharmacy, schizophrenia, cohort studies

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