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      Guidelines for Discontinuation of Antipsychotics in Patients Who Recover From First-Episode Schizophrenia Spectrum Disorders: Derived From the Aggregated Opinions of Asian Network of Early Psychosis Experts and Literature Review

      review-article
      Asian Network of Early Psychosis Writing Group
      International Journal of Neuropsychopharmacology
      Oxford University Press
      Antipsychotics, discontinuation, first episode, GRADE, non-affective psychosis

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          Abstract

          Objective

          Antipsychotic discontinuation has been a long-standing clinical and medicolegal issue. The Asian Network of Early Psychosis developed guidelines for antipsychotic discontinuation in patients who recover from first-episode non-affective psychosis. We reviewed the existing studies and guidelines on antipsychotic discontinuation to develop guidelines for antipsychotic discontinuation in such patients.

          Methods

          We reviewed the relevant studies, reviews, guidelines, and ongoing trials related to antipsychotic discontinuation in patients with first-episode psychosis or schizophrenia. The quality of randomized controlled trials was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach.

          Results

          Most studies had low to very low quality, and 2 had moderate quality. All studies, except 1, advised against antipsychotic discontinuation because of higher relapse rates in the antipsychotic discontinuation group (19%–82% at 1-year follow-up) than the treatment maintenance group compared with the maintenance group. Based on expert opinion and Grading of Recommendations Assessment, Development, and Evaluation evidence of trials, guidelines have been recommended for future discontinuation studies on patients with first-episode schizophrenia spectrum disorders.

          Conclusions

          Currently, there are no recommendations for antipsychotic discontinuation in patients with first-episode schizophrenia spectrum disorders. However, there is a pressing need to conduct more rigorous research in remitted patients using more stringent criteria of full recovery, which can form the basis of guidelines on when and how antipsychotics should be tapered and discontinued. Studies that evaluate the patient characteristics and biomarkers that predict successful antipsychotic discontinuation are also needed.

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          Most cited references91

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          Mortality in mental disorders and global disease burden implications: a systematic review and meta-analysis.

          Despite the potential importance of understanding excess mortality among people with mental disorders, no comprehensive meta-analyses have been conducted quantifying mortality across mental disorders.
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            Remission in schizophrenia: proposed criteria and rationale for consensus.

            New advances in the understanding of schizophrenia etiology, course, and treatment have increased interest on the part of patients, families, advocates, and professionals in the development of consensus-defined standards for clinical status and improvement, including illness remission and recovery. As demonstrated in the area of mood disorders, such standards provide greater clarity around treatment goals, as well as an improved framework for the design and comparison of investigational trials and the subsequent evaluation of the effectiveness of interventions. Unlike the approach to mood disorders, however, the novel application of the concept of standard outcome criteria to schizophrenia must reflect the wide heterogeneity of its long-term course and outcome, as well as the variable effects of different treatments on schizophrenia symptoms. As an initial step in developing operational criteria, an expert working group reviewed available definitions and assessment instruments to provide a conceptual framework for symptomatic, functional, and cognitive domains in schizophrenia as they relate to remission of illness. The first consensus-based operational criteria for symptomatic remission in schizophrenia are based on distinct thresholds for reaching and maintaining improvement, as opposed to change criteria, allowing for alignment with traditional concepts of remission in both psychiatric and nonpsychiatric illness. This innovative approach for standardizing the definition for outcome in schizophrenia will require further examination of its validity and utility, as well as future refinement, particularly in relation to psychosocial and cognitive function and dysfunction. These criteria should facilitate research and support a positive, longer-term approach to studying outcome in patients with schizophrenia.
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              A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time?

              Despite improvements in mental health services in recent decades, it is unclear whether the risk of mortality in schizophrenia has changed over time. To explore the distribution of standardized mortality ratios (SMRs) for people with schizophrenia. Broad search terms were used in MEDLINE, PsychINFO, Web of Science, and Google Scholar to identify all studies that investigated mortality in schizophrenia, published between January 1, 1980, and January 31, 2006. References were also identified from review articles, reference lists, and communication with authors. Population-based studies that reported primary data on deaths in people with schizophrenia. Operationalized criteria were used to extract key study features and mortality data. We examined the distribution of SMRs and pooled selected estimates using random-effects meta-analysis. We identified 37 articles drawn from 25 different nations. The median SMR for all persons for all-cause mortality was 2.58 (10%-90% quantile, 1.18-5.76), with a corresponding random-effects pooled SMR of 2.50 (95% confidence interval, 2.18-2.43). No sex difference was detected. Suicide was associated with the highest SMR (12.86); however, most of the major causes-of-death categories were found to be elevated in people with schizophrenia. The SMRs for all-cause mortality have increased during recent decades (P = .03). With respect to mortality, a substantial gap exists between the health of people with schizophrenia and the general community. This differential mortality gap has worsened in recent decades. In light of the potential for second-generation antipsychotic medications to further adversely influence mortality rates in the decades to come, optimizing the general health of people with schizophrenia warrants urgent attention.
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                Author and article information

                Journal
                Int J Neuropsychopharmacol
                Int J Neuropsychopharmacol
                ijnp
                International Journal of Neuropsychopharmacology
                Oxford University Press (US )
                1461-1457
                1469-5111
                September 2022
                22 April 2022
                22 April 2022
                : 25
                : 9
                : 737-758
                Affiliations
                Department of Psychiatry Unive, University of Hong Kong , Hong Kong, SAR, China
                Department of Psychiatry Unive, University of Hong Kong , Hong Kong, SAR, China
                State Key Laboratory of Brain and Cognitive Sciences, University of Hong Kong , Hong Kong, SAR, China
                Institute of Mental Health , Singapore
                Duke-NUS Medical School , Singapore
                Department of Neuropsychiatry, Toho University School of Medicine , Tokyo, Japan
                Department of Neuropsychiatry, Toho University School of Medicine , Tokyo, Japan
                Tokyo Metropolitan Matsuzawa Hospital , Tokyo, Japan
                Department of Psychiatry, National Taiwan University Hospital , Taipei, Taiwan
                Department of Psychiatry, College of Medicine, National Taiwan University , Taipei, Taiwan
                Department of Neuropsychiatry, Keio University School of Medicine , Tokyo, Japan
                Schizophrenia Program, Centre for Addiction and Mental Health , Toronto, ON, Canada
                Mindlink, Gwangju Bukgu Mental Health Center , Gwangju, Korea
                Department of Psychiatry, Chonnam National University Medical School , Gwangju, Korea
                Department of Psychiatry, Jeonbuk National University Medical School , Jeonju, Korea
                Research Institute of Clinical Medicine of Jeonbuk National University – Biomedical Research Institute of Jeonbuk National University Hospital , Jeonju, Korea
                Author notes
                Correspondence: Dr Young Chul Chung, MD, PhD, Department of Psychiatry, Jeonbuk National University Medical School, Keumam Dong 634-18, Jeonju 561-712, Republic of Korea ( chungyc@ 123456jbnu.ac.kr ).
                Article
                pyac002
                10.1093/ijnp/pyac002
                9515132
                35451023
                5421d4c8-3cee-4782-a566-ca9c2d0922c2
                © The Author(s) 2022. Published by Oxford University Press on behalf of CINP.

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

                History
                : 25 October 2021
                : 01 December 2021
                : 20 April 2022
                : 08 August 2022
                Page count
                Pages: 22
                Funding
                Funded by: Korean Mental Health Technology R&D Project;
                Award ID: HL19C0015
                Funded by: Ministry of Health and Welfare, Republic of Korea;
                Award ID: HI18C2383
                Categories
                Review
                AcademicSubjects/MED00415
                AcademicSubjects/SCI01870

                Pharmacology & Pharmaceutical medicine
                antipsychotics,discontinuation,first episode,grade,non-affective psychosis

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