A Systematic Review and Meta-Analysis of Recovery in Schizophrenia
TL;DR: The proportion of individuals with schizophrenia and related psychoses who met recovery criteria based on both clinical and social domains and if recovery was associated with factors such as gender, economic index of sites, and selected design features of the study was identified.
Abstract: Objective: Our primary aims were (a) to identify the proportion of individuals with schizophrenia and related psychoses who met recovery criteria based on both clinical and social domains and (b) to examine if recovery was associated with factors such as gender, economic index of sites, and selected design features of the study. We also examined if the proportions who met our definition of recovery had changed over time. Method: A comprehensive search strategy was used to identify potential studies, and data were extracted for those that met inclusion criteria. The proportion who met our recovery criteria (improvements in both clinical and social domains and evidence that improvements in at least 1 of these 2 domains had persisted for at least 2 years) was extracted from each study. Meta-regression techniques were used to explore the association between the recovery proportions and the selected variables. Results: We identified 50 studies with data suitable for inclusion. The median proportion (25%–75% quantiles) who met our recovery criteria was 13.5% (8.1%–20.0%). Studies from sites in countries with poorer economic status had higher recovery proportions. However, there were no statistically significant differences when the estimates were stratified according to sex, midpoint of intake period, strictness of the diagnostic criteria, duration of follow-up, or other design features. Conclusions: Based on the best available data, approximately, 1 in 7 individuals with schizophrenia met our criteria for recovery. Despite major changes in treatment options in recent decades, the proportion of recovered cases has not increased.
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TL;DR: Although schizophrenia is a low prevalence disorder, the burden of disease is substantial, and modeling suggests that significant population growth and aging has led to a large and increasing disease burden attributable to schizophrenia, particularly for middle income countries.
Abstract: The global burden of disease (GBD) studies have derived detailed and comparable epidemiological and burden of disease estimates for schizophrenia. We report GBD 2016 estimates of schizophrenia prevalence and burden of disease with disaggregation by age, sex, year, and for all countries. We conducted a systematic review to identify studies reporting the prevalence, incidence, remission, and/or excess mortality associated with schizophrenia. Reported estimates which met our inclusion criteria were entered into a Bayesian meta-regression tool used in GBD 2016 to derive prevalence for 20 age groups, 7 super-regions, 21 regions, and 195 countries and territories. Burden of disease estimates were derived for acute and residual states of schizophrenia by multiplying the age-, sex-, year-, and location-specific prevalence by 2 disability weights representative of the disability experienced during these states. The systematic review found a total of 129 individual data sources. The global age-standardized point prevalence of schizophrenia in 2016 was estimated to be 0.28% (95% uncertainty interval [UI]: 0.24-0.31). No sex differences were observed in prevalence. Age-standardized point prevalence rates did not vary widely across countries or regions. Globally, prevalent cases rose from 13.1 (95% UI: 11.6-14.8) million in 1990 to 20.9 (95% UI: 18.5-23.4) million cases in 2016. Schizophrenia contributes 13.4 (95% UI: 9.9-16.7) million years of life lived with disability to burden of disease globally. Although schizophrenia is a low prevalence disorder, the burden of disease is substantial. Our modeling suggests that significant population growth and aging has led to a large and increasing disease burden attributable to schizophrenia, particularly for middle income countries.
740 citations
Cites methods from "A Systematic Review and Meta-Analys..."
...To be included in our GBD 2016 analysis, studies needed to: (1) make use of a cross-sectional or longitudinal design, the latter with a minimum follow up period of two years to allow sufficient time for observation of outcomes; (2) report estimates of prevalence, incidence, remission, and/or excess mortality for schizophrenia; or provide sufficient data for these to be estimated; (3) utilize the DSM or ICD diagnostic criteria; (4) report estimates of point (current/past month) or past year prevalence (lifetime estimates were excluded as these are at an increased risk of recall bias15–18); (5) report estimates of incidence in the form of hazard rates with person years of follow up as the denominator; (6) report estimates of excess mortality in the form of relative risks or standardized mortality ratio; and (7) make use of a sample which could be considered representative of the community, region, or country under study (inpatient and clinical samples were excluded, except for estimates of mortality)....
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TL;DR: This guideline takes a holistic approach, addressing all aspects of the care of people with schizophrenia and related disorders, not only correct diagnosis and symptom relief but also optimal recovery of social function, and uses a clinical staging model as a framework for recommendations regarding assessment, treatment and ongoing care.
Abstract: Objectives:This guideline provides recommendations for the clinical management of schizophrenia and related disorders for health professionals working in Australia and New Zealand. It aims to encou...
641 citations
Cites background from "A Systematic Review and Meta-Analys..."
...Despite the high risk of chronic disability, loss of developmental potential and diminished quality of life associated with schizophrenia, and despite widespread neglect of the care of people with schizophrenia around the world, about one in seven of those who meet the diagnostic criteria for schizophrenia ultimately attain nearly complete recovery (Jaaskelainen et al., 2013)....
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...…diminished quality of life associated with schizophrenia, and despite widespread neglect of the care of people with schizophrenia around the world, about one in seven of those who meet the diagnostic criteria for schizophrenia ultimately attain nearly complete recovery (Jaaskelainen et al., 2013)....
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TL;DR: In this article , a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals was conducted, and the authors reported common variant associations at 287 distinct genomic loci.
Abstract: Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies. A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.
558 citations
TL;DR: Comprehensive care for first-episode psychosis can be implemented in U.S. community clinics and improves functional and clinical outcomes, and effects are more pronounced for those with shorter duration of untreated psychosis.
Abstract: Objective:The primary aim of this study was to compare the impact of NAVIGATE, a comprehensive, multidisciplinary, team-based treatment approach for first-episode psychosis designed for implementation in the U.S. health care system, with community care on quality of life.Method:Thirty-four clinics in 21 states were randomly assigned to NAVIGATE or community care. Diagnosis, duration of untreated psychosis, and clinical outcomes were assessed via live, two-way video by remote, centralized raters masked to study design and treatment. Participants (mean age, 23) with schizophrenia and related disorders and ≤6 months of antipsychotic treatment (N=404) were enrolled and followed for ≥2 years. The primary outcome was the total score of the Heinrichs-Carpenter Quality of Life Scale, a measure that includes sense of purpose, motivation, emotional and social interactions, role functioning, and engagement in regular activities.Results:The 223 recipients of NAVIGATE remained in treatment longer, experienced greater ...
549 citations
Cites background from "A Systematic Review and Meta-Analys..."
...Introduction Schizophrenia is associated with enormous personal suffering, disability, family burden, premature death, and societal cost (1,2)....
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...Site eligibility criteria included (1) experience treating people with schizophrenia; (2) interest in offering early intervention services for first episode psychosis; (3) sufficient staff to implement the experimental intervention; (4) ability to recruit an adequate number of subjects; and (5) institutional assurance that research assessments would be completed....
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...Subject attrition was minimized though (1) regular contact by the coordinating team with research staff to reinforce retention efforts and (2) a progressive reimbursement schedule for trial participants completing outcome assessments....
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TL;DR: The small but mostly consistent correlation between long DUP and poor outcome indicates that early intervention in psychosis may have at least subtle positive effects on the long-term course of illness.
Abstract: Background
Duration of untreated psychosis (DUP) is one of the few potentially modifiable predictors of outcomes of schizophrenia. Long DUP as a predictor of poor short-term outcome has been addressed in previous meta-analyses, but the long-term effects of DUP remain unclear.
Aims
To analyse the associations between DUP and long-term outcomes of schizophrenia.
Method
A systematic literature search was performed using seven electronic databases and manual searches. Random effects weighted meta-analysis with correlation coefficients was used to pool the results.
Results
We identified 3493 unique publications, from which 33 samples met our predefined selection criteria. Long DUP correlated statistically significantly with poor general symptomatic outcome, more severe positive and negative symptoms, lesser likelihood of remission and poor social functioning and global outcome (correlations 0.13-0.18). Long DUP was not associated with employment, quality of life or hospital treatment.
Conclusions
The small but mostly consistent correlation between long DUP and poor outcome indicates that early intervention in psychosis may have at least subtle positive effects on the long-term course of illness.
494 citations
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TL;DR: Moher et al. as mentioned in this paper introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses, which is used in this paper.
Abstract: David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses
62,157 citations
Journal Article•
TL;DR: The QUOROM Statement (QUality Of Reporting Of Meta-analyses) as mentioned in this paper was developed to address the suboptimal reporting of systematic reviews and meta-analysis of randomized controlled trials.
Abstract: Systematic reviews and meta-analyses have become increasingly important in health care. Clinicians read them to keep up to date with their field,1,2 and they are often used as a starting point for developing clinical practice guidelines. Granting agencies may require a systematic review to ensure there is justification for further research,3 and some health care journals are moving in this direction.4 As with all research, the value of a systematic review depends on what was done, what was found, and the clarity of reporting. As with other publications, the reporting quality of systematic reviews varies, limiting readers' ability to assess the strengths and weaknesses of those reviews.
Several early studies evaluated the quality of review reports. In 1987, Mulrow examined 50 review articles published in 4 leading medical journals in 1985 and 1986 and found that none met all 8 explicit scientific criteria, such as a quality assessment of included studies.5 In 1987, Sacks and colleagues6 evaluated the adequacy of reporting of 83 meta-analyses on 23 characteristics in 6 domains. Reporting was generally poor; between 1 and 14 characteristics were adequately reported (mean = 7.7; standard deviation = 2.7). A 1996 update of this study found little improvement.7
In 1996, to address the suboptimal reporting of meta-analyses, an international group developed a guidance called the QUOROM Statement (QUality Of Reporting Of Meta-analyses), which focused on the reporting of meta-analyses of randomized controlled trials.8 In this article, we summarize a revision of these guidelines, renamed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), which have been updated to address several conceptual and practical advances in the science of systematic reviews (Box 1).
Box 1
Conceptual issues in the evolution from QUOROM to PRISMA
46,935 citations
TL;DR: A new quantity is developed, I 2, which the authors believe gives a better measure of the consistency between trials in a meta-analysis, which is susceptible to the number of trials included in the meta- analysis.
Abstract: Cochrane Reviews have recently started including the quantity I 2 to help readers assess the consistency of the results of studies in meta-analyses. What does this new quantity mean, and why is assessment of heterogeneity so important to clinical practice?
Systematic reviews and meta-analyses can provide convincing and reliable evidence relevant to many aspects of medicine and health care.1 Their value is especially clear when the results of the studies they include show clinically important effects of similar magnitude. However, the conclusions are less clear when the included studies have differing results. In an attempt to establish whether studies are consistent, reports of meta-analyses commonly present a statistical test of heterogeneity. The test seeks to determine whether there are genuine differences underlying the results of the studies (heterogeneity), or whether the variation in findings is compatible with chance alone (homogeneity). However, the test is susceptible to the number of trials included in the meta-analysis. We have developed a new quantity, I 2, which we believe gives a better measure of the consistency between trials in a meta-analysis.
Assessment of the consistency of effects across studies is an essential part of meta-analysis. Unless we know how consistent the results of studies are, we cannot determine the generalisability of the findings of the meta-analysis. Indeed, several hierarchical systems for grading evidence state that the results of studies must be consistent or homogeneous to obtain the highest grading.2–4
Tests for heterogeneity are commonly used to decide on methods for combining studies and for concluding consistency or inconsistency of findings.5 6 But what does the test achieve in practice, and how should the resulting P values be interpreted?
A test for heterogeneity examines the null hypothesis that all studies are evaluating the same effect. The usual test statistic …
45,105 citations
Book•
27 Apr 200910,518 citations