Despite convincing evidence of short-term symptom control and functional recovery of patients with psychosis after receiving early intervention (EI) services, little is known about the long-term outcomes of EI for these patients. This review aims to evaluate the effectiveness of EI services in improving long-term outcomes of patients with psychosis. A systematic literature search was conducted on PubMed, PsycINFO, Scopus, Medline, CINAHL, BIOSIS, and EMBASE electronic databases to identify studies that evaluated long-term outcomes of patients with psychosis measured 5 years or beyond after entering the EI service. Of 13,005 articles returned from the search, 14 eligible articles reporting study cohorts from nine EI services in seven countries and regions were identified. Data on study design, patient characteristics, intervention components, and outcomes were extracted and reviewed. Only a few studies reported better longitudinal outcomes for negative symptoms, mortality, employment, and hospitalization in patients received EI services. However, results from cross-sectional measurements provided little evidence for long-term impacts of EI services on clinical and functional outcomes. A dilution effect of benefits over time was also demonstrated in several studies. This review highlights the gap in current EI service provision and suggests possible future directions for service improvement and further research.
IMPORTANCE: Follow-up of participants in randomized trials may be limited by logistic and financial factors. Some important randomized trials have been extended well beyond their original follow-up period by linkage of individual participant information to routinely collected data held in administrative records and registries.
OBJECTIVE: To perform a scoping review of randomized clinical trials extended by record linkage to characterize this literature and explore any additional insights into treatment effectiveness provided by long-term follow-up using record linkage.
DATA SOURCES: A literature search in Embase, CINAHL, MEDLINE, and the Cochrane Register of Controlled Trials was performed for the period January 1, 1945, through November 25, 2016.
STUDY SELECTION: Various combinations of search terms were used, as there is no accepted terminology. Determination of study eligibility and extraction of information about trial characteristics and outcomes, for both original and extended trial reports, were performed in duplicate.
DATA EXTRACTION AND SYNTHESIS: Assessment of study eligibility and data extraction were performed independently by 2 reviewers. All analyses were descriptive.
MAIN OUTCOMES AND MEASURES: Outcomes in the pairs of original and extended trials were categorized according to whether any benefits or harms from interventions were sustained, were lost, or emerged during long-term follow-up.
RESULTS: A total of 113 extended trials were included in the study. Linkage to administrative and registry data extended follow-up by between 1 and 55 years. The most common interventions were pharmaceuticals (47 [41.6%]), surgery (19 [16.8%]), and disease screening (19 [16.8%]). End points most frequently studied through record linkage included mortality (88 [77.9%]), cancer (41 [36.3%]), and cardiovascular events (37 [32.7%]). One hundred four trial extensions (92.0%) were analyzed according to the original trial randomization. The reports provided details of 155 analyses of study outcomes. Seventy-four analyses (47.7%) identified statistically significant benefits in the trial extension phase. In 21 of these (28.4%), benefits were significant only in this period. Null results in both the original and extended trials were seen in 34 of the analyses (21.9%). Loss of significant benefits of an intervention were seen in 12 analyses (7.7%). Statistically significant harms were seen in 16 trial extension analyses (10.3%), and in 14 of these (87.5%), the harms were significant only in the trial extension phase.
CONCLUSIONS AND RELEVANCE: Trial extension by linkage to routinely collected data is a versatile underused approach that may add critical insights beyond those of the original trial. Some beneficial and harmful outcomes of interventions are captured only in the extension phase of randomized trials.
IMPORTANCE: The value of early intervention in psychosis and allocation of public resources has long been debated because outcomes in people with schizophrenia spectrum disorders have remained suboptimal.
OBJECTIVE: To compare early intervention services (EIS) with treatment as usual (TAU) for early-phase psychosis.
DATA SOURCES: Systematic literature search of PubMed, PsycINFO, EMBASE, and ClinicalTrials.gov without language restrictions through June 6, 2017.
STUDY SELECTION: Randomized trials comparing EIS vs TAU in first-episode psychosis or early-phase schizophrenia spectrum disorders.
DATA EXTRACTION AND SYNTHESIS: This systematic review was conducted according to PRISMA guidelines. Three independent investigators extracted data for a random-effects meta-analysis and prespecified subgroup and meta-regression analyses.
MAIN OUTCOMES AND MEASURES: The coprimary outcomes were all-cause treatment discontinuation and at least 1 psychiatric hospitalization during the treatment period.
RESULTS: Across 10 randomized clinical trials (mean [SD] trial duration, 16.2 [7.4] months; range, 9-24 months) among 2176 patients (mean [SD] age, 27.5 [4.6] years; 1355 [62.3%] male), EIS was associated with better outcomes than TAU at the end of treatment for all 13 meta-analyzable outcomes. These outcomes included the following: all-cause treatment discontinuation (risk ratio [RR], 0.70; 95% CI, 0.61-0.80; P < .001), at least 1 psychiatric hospitalization (RR, 0.74; 95% CI, 0.61-0.90; P = .003), involvement in school or work (RR, 1.13; 95% CI, 1.03-1.24; P = .01), total symptom severity (standardized mean difference [SMD], -0.32; 95% CI, -0.47 to -0.17; P < .001), positive symptom severity (SMD, -0.22; 95% CI, -0.32 to -0.11; P < .001), and negative symptom severity (SMD, -0.28; 95% CI, -0.42 to -0.14; P < .001). Superiority of EIS regarding all outcomes was evident at 6, 9 to 12, and 18 to 24 months of treatment (except for general symptom severity and depressive symptom severity at 18-24 months).
CONCLUSIONS AND RELEVANCE: In early-phase psychosis, EIS are superior to TAU across all meta-analyzable outcomes. These results support the need for funding and use of EIS in patients with early-phase psychosis.
OBJECTIVES: This systematic review (SR) provides evidence on pharmacological and psychosocial treatments for schizophrenia.
DATA SOURCES: MEDLINE®, the Cochrane Library databases, PsycINFO®, and included studies through February 2017.
STUDY SELECTION: We included studies comparing second-generation antipsychotics (SGA) with each other or with a first-generation antipsychotic (FGA) and studies comparing psychosocial interventions with usual care in adults with schizophrenia.
DATA EXTRACTION: We extracted study design, year, setting, country, sample size, eligibility criteria, population, clinical and intervention characteristics, results, and funding source.
RESULTS: We included 1 SR of 138 trials (N=47,189) and 24 trials (N=6,672) for SGAs versus SGAs, 1 SR of 111 trials (N=118,503) and 5 trials (N=1,055) for FGAs versus SGAs, and 13 SRs of 271 trials (N=25,050) and 27 trials (n=6,404) for psychosocial interventions. Trials were mostly fair quality and strength of evidence was low or moderate. For drug therapy, the majority of the head-to-head evidence was on older SGAs, with sparse data on SGAs approved in the last 10 years (asenapine, lurasidone, iloperidone, cariprazine, brexpiprazole) and recent long-acting injection (LAI) formulations of aripiprazole and paliperidone. Older SGAs were similar in measures of function, quality of life, mortality, and overall adverse events, except that risperidone LAI had better social function than quetiapine. Core illness symptoms were improved more with olanzapine and risperidone than asenapine, quetiapine, and ziprasidone, and more with paliperidone than lurasidone and iloperidone; all were superior to placebo. Risperidone LAI and olanzapine had less withdrawal due to adverse events. Compared with olanzapine and risperidone, haloperidol, the most studied FGA, had similar improvement in core illness symptoms, negative symptoms, symptom response, and remission but greater incidence of adverse event outcomes. In comparison with usual care, most psychosocial interventions reviewed were more effective in improving intervention-targeted outcomes, including core illness symptoms. Various functional outcomes were improved more with assertive community treatment, cognitive behavioral therapy, family interventions, psychoeducation, social skills training, supported employment, and early interventions for first episode psychosis (FEP) than with usual care. Quality of life was improved more with cognitive behavioral therapy and early interventions for FEP than usual care. Relapse was reduced with family interventions, psychoeducation, illness self-management, family interventions, and early interventions for FEP.
CONCLUSIONS: Most comparative evidence on pharmacotherapy relates to the older drugs, with clozapine, olanzapine, and risperidone superior on more outcomes than other SGAs. Older SGAs were similar to haloperidol on benefit outcomes but had fewer adverse event outcomes. Most psychosocial interventions improved functional outcomes, quality of life, and core illness symptoms, and several reduced relapse compared with usual care.
BACKGROUND: Intensive Case Management (ICM) is a community-based package of care aiming to provide long-term care for severely mentally ill people who do not require immediate admission. Intensive Case Management evolved from two original community models of care, Assertive Community Treatment (ACT) and Case Management (CM), where ICM emphasises the importance of small caseload (fewer than 20) and high-intensity input.
OBJECTIVES: To assess the effects of ICM as a means of caring for severely mentally ill people in the community in comparison with non-ICM (caseload greater than 20) and with standard community care. We did not distinguish between models of ICM. In addition, to assess whether the effect of ICM on hospitalisation (mean number of days per month in hospital) is influenced by the intervention's fidelity to the ACT model and by the rate of hospital use in the setting where the trial was conducted (baseline level of hospital use).
SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Register (last update search 10 April 2015).
SELECTION CRITERIA: All relevant randomised clinical trials focusing on people with severe mental illness, aged 18 to 65 years and treated in the community care setting, where ICM is compared to non-ICM or standard care.
DATA COLLECTION AND ANALYSIS: At least two review authors independently selected trials, assessed quality, and extracted data. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated mean difference (MD) between groups and its 95% CI. We employed a random-effects model for analyses.We performed a random-effects meta-regression analysis to examine the association of the intervention's fidelity to the ACT model and the rate of hospital use in the setting where the trial was conducted with the treatment effect. We assessed overall quality for clinically important outcomes using the GRADE approach and investigated possible risk of bias within included trials.
MAIN RESULTS: The 2016 update included two more studies (n = 196) and more publications with additional data for four already included studies. The updated review therefore includes 7524 participants from 40 randomised controlled trials (RCTs). We found data relevant to two comparisons: ICM versus standard care, and ICM versus non-ICM. The majority of studies had a high risk of selective reporting. No studies provided data for relapse or important improvement in mental state.1. ICM versus standard careWhen ICM was compared with standard care for the outcome service use, ICM slightly reduced the number of days in hospital per month (n = 3595, 24 RCTs, MD -0.86, 95% CI -1.37 to -0.34,low-quality evidence). Similarly, for the outcome global state, ICM reduced the number of people leaving the trial early (n = 1798, 13 RCTs, RR 0.68, 95% CI 0.58 to 0.79, low-quality evidence). For the outcome adverse events, the evidence showed that ICM may make little or no difference in reducing death by suicide (n = 1456, 9 RCTs, RR 0.68, 95% CI 0.31 to 1.51, low-quality evidence). In addition, for the outcome social functioning, there was uncertainty about the effect of ICM on unemployment due to very low-quality evidence (n = 1129, 4 RCTs, RR 0.70, 95% CI 0.49 to 1.0, very low-quality evidence).2. ICM versus non-ICMWhen ICM was compared with non-ICM for the outcome service use, there was moderate-quality evidence that ICM probably makes little or no difference in the average number of days in hospital per month (n = 2220, 21 RCTs, MD -0.08, 95% CI -0.37 to 0.21, moderate-quality evidence) or in the average number of admissions (n = 678, 1 RCT, MD -0.18, 95% CI -0.41 to 0.05, moderate-quality evidence) compared to non-ICM. Similarly, the results showed that ICM may reduce the number of participants leaving the intervention early (n = 1970, 7 RCTs, RR 0.70, 95% CI 0.52 to 0.95,low-quality evidence) and that ICM may make little or no difference in reducing death by suicide (n = 1152, 3 RCTs, RR 0.88, 95% CI 0.27 to 2.84, low-quality evidence). Finally, for the outcome social functioning, there was uncertainty about the effect of ICM on unemployment as compared to non-ICM (n = 73, 1 RCT, RR 1.46, 95% CI 0.45 to 4.74, very low-quality evidence).3. Fidelity to ACTWithin the meta-regression we found that i.) the more ICM is adherent to the ACT model, the better it is at decreasing time in hospital ('organisation fidelity' variable coefficient -0.36, 95% CI -0.66 to -0.07); and ii.) the higher the baseline hospital use in the population, the better ICM is at decreasing time in hospital ('baseline hospital use' variable coefficient -0.20, 95% CI -0.32 to -0.10). Combining both these variables within the model, 'organisation fidelity' is no longer significant, but the 'baseline hospital use' result still significantly influences time in hospital (regression coefficient -0.18, 95% CI -0.29 to -0.07, P = 0.0027).
AUTHORS' CONCLUSIONS: Based on very low- to moderate-quality evidence, ICM is effective in ameliorating many outcomes relevant to people with severe mental illness. Compared to standard care, ICM may reduce hospitalisation and increase retention in care. It also globally improved social functioning, although ICM's effect on mental state and quality of life remains unclear. Intensive Case Management is at least valuable to people with severe mental illnesses in the subgroup of those with a high level of hospitalisation (about four days per month in past two years). Intensive Case Management models with high fidelity to the original team organisation of ACT model were more effective at reducing time in hospital.However, it is unclear what overall gain ICM provides on top of a less formal non-ICM approach.We do not think that more trials comparing current ICM with standard care or non-ICM are justified, however we currently know of no review comparing non-ICM with standard care, and this should be undertaken.
Aims. Young adults with early psychosis want to pursue normal roles - education and employment. This paper summarises the empirical literature on the effectiveness of early intervention programmes for employment and education outcomes. Methods. We conducted a systematic review of employment/education outcomes for early intervention programmes, distinguishing three programme types: (1) those providing supported employment, (2) those providing unspecified vocational services and (3) those without vocational services. We summarised findings for 28 studies. Results. Eleven studies evaluated early intervention programmes providing supported employment. In eight studies that reported employment outcomes separately from education outcomes, the employment rate during follow-up for supported employment patients was 49%, compared with 29% for patients receiving usual services. The two groups did not differ on enrolment in education. In four controlled studies, meta-analysis showed that the employment rate for supported employment participants was significantly higher than for control participants, odds ratio = 3.66 [1.93-6.93], p < 0.0001. Five studies (four descriptive and one quasi-experimental) of early intervention programmes evaluating unspecified vocational services were inconclusive. Twelve studies of early intervention programmes without vocational services were methodologically heterogeneous, using diverse methods for evaluating vocational/educational outcomes and precluding a satisfactory meta-analytic synthesis. Among studies with comparison groups, 7 of 11 (64%) reported significant vocational/education outcomes favouring early intervention over usual services. Conclusions. In early intervention programmes, supported employment moderately increases employment rates but not rates of enrolment in education. These improvements are in addition to the modest effects early programmes alone have on vocational/educational outcomes compared with usual services.
OBJECTIVES: To review and synthesize the currently available research on whether early intervention for psychosis programs reduce the use of inpatient services. METHODS: A systematic review was conducted using keywords searches on PubMed, Embase (Ovid), PsycINFO (ProQuest), Scopus, CINAHL (EBSCO), Social Work Abstracts (EBSCO), Social Science Citations Index (Web of Science), Sociological Abstracts (ProQuest), and Child Development & Adolescent Studies (EBSCO). To be included, studies had to be peer-reviewed publications in English, examining early intervention programs using a variant of assertive community treatment, with a control/comparison group, and reporting inpatient service use outcomes. The primary outcome extracted number hospitalized and total N. Secondary outcome extracted means and standard deviations. Data were pooled using random effects models. Primary outcome was the occurrence of any hospitalization during treatment. A secondary outcome was the average bed-days used during treatment period. RESULTS: Fifteen projects were identified and included in the study. Results of meta-analysis supported the occurrence of a positive effect for intervention for both outcome measures (any hospitalization OR.: 0.33; 95% CI 0.18-0.63, bed-days usage SMD -0.38, 95% CI -0.53 to -0.24). There was significant heterogeneity of effect across the studies. This heterogeneity is due to a handful of studies with unusually positive responses. CONCLUSION: These results suggest that early intervention programs are superior to standard of care, with respect to reducing inpatient service usage. Wider use of these programs may prevent the occurrence of admission for patients experiencing the onset of psychotic symptoms.
BACKGROUND: In many countries, national, regional and local inter- and intra-agency collaborations have been introduced to improve health outcomes. Evidence is needed on the effectiveness of locally developed partnerships which target changes in health outcomes and behaviours.
OBJECTIVES: To evaluate the effects of interagency collaboration between local health and local government agencies on health outcomes in any population or age group.
SEARCH METHODS: We searched the Cochrane Public Health Group Specialised Register, AMED, ASSIA, CENTRAL, CINAHL, DoPHER, EMBASE, ERIC, HMIC, IBSS, MEDLINE, MEDLINE In-Process, OpenGrey, PsycINFO, Rehabdata, Social Care Online, Social Services Abstracts, Sociological Abstracts, TRoPHI and Web of Science from 1966 through to January 2012. 'Snowballing' methods were used, including expert contact, citation tracking, website searching and reference list follow-up.
SELECTION CRITERIA: Randomized controlled trials (RCTs), controlled clinical trials (CCTs), controlled before-and-after studies (CBAs) and interrupted time series (ITS) where the study reported individual health outcomes arising from interagency collaboration between health and local government agencies compared to standard care. Studies were selected independently in duplicate, with no restriction on population subgroup or disease.
DATA COLLECTION AND ANALYSIS: Two authors independently conducted data extraction and assessed risk of bias for each study.
MAIN RESULTS: Sixteen studies were identified (28,212 participants). Only two were considered to be at low risk of bias. Eleven studies contributed data to the meta-analyses but a narrative synthesis was undertaken for all 16 studies. Six studies examined mental health initiatives, of which one showed health benefit, four showed modest improvement in one or more of the outcomes measured but no clear overall health gain, and one showed no evidence of health gain. Four studies considered lifestyle improvements, of which one showed some limited short-term improvements, two failed to show health gains for the intervention population, and one showed more unhealthy lifestyle behaviours persisting in the intervention population. Three studies considered chronic disease management and all failed to demonstrate health gains. Three studies considered environmental improvements and adjustments, of which two showed some health improvements and one did not.
Meta-analysis of three studies exploring the effect of collaboration on mortality showed no effect (pooled relative risk of 1.04 in favour of control, 95% CI 0.92 to 1.17). Analysis of five studies (with high heterogeneity) looking at the effect of collaboration on mental health resulted in a standardised mean difference of -0.28, a small effect favouring the intervention (95% CI -0.51 to -0.06). From two studies, there was a statistically significant but clinically modest improvement in the global assessment of function symptoms score scale, with a pooled mean difference (on a scale of 1 to 100) of -2.63 favouring the intervention (95% CI -5.16 to -0.10).
For physical health (6 studies) and quality of life (4 studies) the results were not statistically significant, the standardised mean differences were -0.01 (95% CI -0.10 to 0.07) and -0.08 (95% CI -0.44 to 0.27), respectively.
AUTHORS' CONCLUSIONS: Collaboration between local health and local government is commonly considered best practice. However, the review did not identify any reliable evidence that interagency collaboration, compared to standard services, necessarily leads to health improvement. A few studies identified component benefits but these were not reflected in overall outcome scores and could have resulted from the use of significant additional resources. Although agencies appear enthusiastic about collaboration, difficulties in the primary studies and incomplete implementation of initiatives have prevented the development of a strong evidence base. If these weaknesses are addressed in future studies (for example by providing greater detail on the implementation of programmes; using more robust designs, integrated process evaluations to show how well the partners of the collaboration worked together, and measurement of health outcomes) it could provide a better understanding of what might work and why. It is possible that local collaborative partnerships delivering environmental Interventions may result in health gain but the evidence base for this is very limited.
Evaluations of interagency collaborative arrangements face many challenges. The results demonstrate that collaborative community partnerships can be established to deliver interventions but it is important to agree goals, methods of working, monitoring and evaluation before implementation to protect programme fidelity and increase the potential for effectiveness.
OBJECTIVE: Early-intervention units have proliferated over the last decade, justified in terms of cost as well as treatment effect. Strong claims for extension of these programmes on economic grounds motivate a systematic review of economic evaluations of early-intervention programmes.
METHOD: Searches were undertaken in the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and PsycINFO with keywords including 'early intervention', 'ultra-high risk', 'prodrome', 'cost-effectiveness', 'psychosis', 'economic', and 'at-risk mental state'. Relevant journals, editorials, and the references of retrieved articles were hand-searched for appropriate research.
RESULTS: Eleven articles were included in the review. The more rigorous research (two randomized control trials and two quasi-experimental studies) suggested no difference in resource utilization or costs between early-intervention and treatment-as-usual groups. One small case-control study with evidence of significant bias concluded annual early-intervention costs were one-third of treatment-as-usual costs. Modelling studies projected reduced costs of early intervention but were based on assumptions since definitively revised. Cost-effectiveness analyses did not strongly support the cost-effectiveness of early intervention. No studies appropriately valued outpatient costs or addressed the feasibility of realizing reduced hospitalization in reduced costs.
CONCLUSIONS: The published literature does not support the contention that early intervention for psychosis reduces costs or achieves cost-effectiveness. Past failed attempts to reduce health costs by reducing hospitalization, and increased outpatient costs in early-intervention programmes suggest such programmes may increase costs. Future economic evaluation of early-intervention programmes would need to correctly value outpatient costs and accommodate uncertainty regarding reduced hospitalization costs, perhaps by sensitivity analysis. The current research hints that cost differences may be greater early in treatment and in patients with more severe illness.
Despite convincing evidence of short-term symptom control and functional recovery of patients with psychosis after receiving early intervention (EI) services, little is known about the long-term outcomes of EI for these patients. This review aims to evaluate the effectiveness of EI services in improving long-term outcomes of patients with psychosis. A systematic literature search was conducted on PubMed, PsycINFO, Scopus, Medline, CINAHL, BIOSIS, and EMBASE electronic databases to identify studies that evaluated long-term outcomes of patients with psychosis measured 5 years or beyond after entering the EI service. Of 13,005 articles returned from the search, 14 eligible articles reporting study cohorts from nine EI services in seven countries and regions were identified. Data on study design, patient characteristics, intervention components, and outcomes were extracted and reviewed. Only a few studies reported better longitudinal outcomes for negative symptoms, mortality, employment, and hospitalization in patients received EI services. However, results from cross-sectional measurements provided little evidence for long-term impacts of EI services on clinical and functional outcomes. A dilution effect of benefits over time was also demonstrated in several studies. This review highlights the gap in current EI service provision and suggests possible future directions for service improvement and further research.
