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Systematic review

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Journal Psychiatry research
Year 2023
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The population of persons of color (POC) are increasing in the United States. Unfortunately, POC are significantly impacted by serious mental illness; psychosis represents a mental health disparity among POC. Fortunately, first episode coordinated specialty care (CSC) is an effective treatment for individuals who are in the early phases of a psychotic disorder. This systematic review of the literature examined POC inclusion rates in randomized controlled trials (RCT) examining First Episode Psychosis (FEP) programs. Our review yielded seven articles that met inclusion criteria. Our findings were mixed-researchers conducting RCTs on FEP programs did an excellent job including African American participants suggesting that findings from RCTs on FEP programs may generalize to African American participants. Regarding Latines, they were broadly underrepresented in RCTs on FEP CSC. Based on the data, we cannot definitively conclude to what extent findings from RCTs on FEP CSC generalize to Latines although results from studies that included a reasonable number of Latines offer promising results. Asians were overrepresented in three of the seven studies included in this review; thus it seems that the findings from RCTs on FEP CSC generalize to the Asian population in the United States.

Systematic review

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Journal The Cochrane database of systematic reviews
Year 2020
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BACKGROUND: Psychosis is an illness characterised by the presence of hallucinations and delusions that can cause distress or a marked change in an individual's behaviour (e.g. social withdrawal, flat or blunted effect). A first episode of psychosis (FEP) is the first time someone experiences these symptoms that can occur at any age, but the condition is most common in late adolescence and early adulthood. This review is concerned with first episode psychosis (FEP) and the early stages of a psychosis, referred to throughout this review as 'recent-onset psychosis.' Specialised early intervention (SEI) teams are community mental health teams that specifically treat people who are experiencing, or have experienced a recent-onset psychosis. The purpose of SEI teams is to intensively treat people with psychosis early in the course of the illness with the goal of increasing the likelihood of recovery and reducing the need for longer-term mental health treatment. SEI teams provide a range of treatments including medication, psychotherapy, psychoeducation, and occupational, educational and employment support, augmented by assertive contact with the service user and small caseloads. Treatment is time limited, usually offered for two to three years, after which service users are either discharged to primary care or transferred to a standard adult community mental health team. A previous Cochrane Review of SEI found preliminary evidence that SEI may be superior to standard community mental health care (described as 'treatment as usual (TAU)' in this review) but these recommendations were based on data from only one trial. This review updates the evidence for the use of SEI services. OBJECTIVES: To compare specialised early intervention (SEI) teams to treatment as usual (TAU) for people with recent-onset psychosis. SEARCH METHODS: On 3 October 2018 and 22 October 2019, we searched Cochrane Schizophrenia's study-based register of trials, including registries of clinical trials. SELECTION CRITERIA: We selected all randomised controlled trials (RCTs) comparing SEI with TAU for people with recent-onset psychosis. We entered trials meeting these criteria and reporting useable data as included studies. DATA COLLECTION AND ANALYSIS: We independently inspected citations, selected studies, extracted data and appraised study quality. For binary outcomes we calculated the risk ratios (RRs) and their 95% confidence intervals (CIs). For continuous outcomes we calculated the mean difference (MD) and their 95% CIs, or if assessment measures differed for the same construct, we calculated the standardised mean difference (SMD) with 95% CIs. We assessed risk of bias for included studies and created a 'Summary of findings' table using the GRADE approach. MAIN RESULTS: We included three RCTs and one cluster-RCT with a total of 1145 participants. The mean age in the trials was between 23.1 years (RAISE) and 26.6 years (OPUS). The included participants were 405 females (35.4%) and 740 males (64.6%). All trials took place in community mental healthcare settings. Two trials reported on recovery from psychosis at the end of treatment, with evidence that SEI team care may result in more participants in recovery than TAU at the end of treatment (73% versus 52%; RR 1.41, 95% CI 1.01 to 1.97; 2 studies, 194 participants; low-certainty evidence). Three trials provided data on disengagement from services at the end of treatment, with fewer participants probably being disengaged from mental health services in SEI (8%) in comparison to TAU (15%) (RR 0.50, 95% CI 0.31 to 0.79; 3 studies, 630 participants; moderate-certainty evidence). There was low-certainty evidence that SEI may result in fewer admissions to psychiatric hospital than TAU at the end of treatment (52% versus 57%; RR 0.91, 95% CI 0.82 to 1.00; 4 studies, 1145 participants) and low-certainty evidence that SEI may result in fewer psychiatric hospital days (MD -27.00 days, 95% CI -53.68 to -0.32; 1 study, 547 participants). Two trials reported on general psychotic symptoms at the end of treatment, with no evidence of a difference between SEI and TAU, although this evidence is very uncertain (SMD -0.41, 95% CI -4.58 to 3.75; 2 studies, 304 participants; very low-certainty evidence). A different pattern was observed in assessment of general functioning with an end of trial difference that may favour SEI (SMD 0.37, 95% CI 0.07 to 0.66; 2 studies, 467 participants; low-certainty evidence). It was uncertain whether the use of SEI resulted in fewer deaths due to all-cause mortality at end of treatment (RR 0.21, 95% CI 0.04 to 1.20; 3 studies, 741 participants; low-certainty evidence). There was low risk of bias for random sequence generation and allocation concealment in three of the four included trials; the remaining trial had unclear risk of bias. Due to the nature of the intervention, we considered all trials at high risk of bias for blinding of participants and personnel. Two trials had low risk of bias and two trials had high risk of bias for blinding of outcomes assessments. Three trials had low risk of bias for incomplete outcome data, while one trial had high risk of bias. Two trials had low risk of bias, one trial had high risk of bias, and one had unclear risk of bias for selective reporting. AUTHORS' CONCLUSIONS: There is evidence that SEI may provide benefits to service users during treatment compared to TAU. These benefits probably include fewer disengagements from mental health services (moderate-certainty evidence), and may include small reductions in psychiatric hospitalisation (low-certainty evidence), and a small increase in global functioning (low-certainty evidence) and increased service satisfaction (moderate-certainty evidence). The evidence regarding the effect of SEI over TAU after treatment has ended is uncertain. Further evidence investigating the longer-term outcomes of SEI is needed. Furthermore, all the eligible trials included in this review were conducted in high-income countries, and it is unclear whether these findings would translate to low- and middle-income countries, where both the intervention and the comparison conditions may be different.

Systematic review

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Journal International review of psychiatry (Abingdon, England)
Year 2019
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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.

Systematic review

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Journal JAMA network open
Year 2018
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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.

Systematic review

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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.

Systematic review

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Book AHRQ Comparative Effectiveness Reviews
Year 2017
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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.

Systematic review

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Journal World Psychiatry
Year 2017
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Outcomes of psychotic disorders are associated with high personal, familiar, societal and clinical burden. There is thus an urgent clinical and societal need for improving those outcomes. Recent advances in research knowledge have opened new opportunities for ameliorating outcomes of psychosis during its early clinical stages. This paper critically reviews these opportunities, summarizing the state‐of‐the‐art knowledge and focusing on recent discoveries and future avenues for first episode research and clinical interventions. Candidate targets for primary universal prevention of psychosis at the population level are discussed. Potentials offered by primary selective prevention in asymptomatic subgroups (stage 0) are presented. Achievements of primary selected prevention in individuals at clinical high risk for psychosis (stage 1) are summarized, along with challenges and limitations of its implementation in clinical practice. Early intervention and secondary prevention strategies at the time of a first episode of psychosis (stage 2) are critically discussed, with a particular focus on minimizing the duration of untreated psychosis, improving treatment response, increasing patients’ satisfaction with treatment, reducing illicit substance abuse and preventing relapses. Early intervention and tertiary prevention strategies at the time of an incomplete recovery (stage 3) are further discussed, in particular with respect to addressing treatment resistance, improving well‐being and social skills with reduction of burden on the family, treatment of comorbid substance use, and prevention of multiple relapses and disease progression. In conclusion, to improve outcomes of a complex, heterogeneous syndrome such as psychosis, it is necessary to globally adopt complex models integrating a clinical staging framework and coordinated specialty care programmes that offer pre‐emptive interventions to high‐risk groups identified across the early stages of the disorder. Only a systematic implementation of these models of care in the national health care systems will render these strategies accessible to the 23 million people worldwide suffering from the most severe psychiatric disorders.

Systematic review

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Journal Cochrane Database of Systematic Reviews
Year 2017
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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.

Systematic review

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Authors Bond GR , Drake RE , Luciano A
Journal Epidemiology and psychiatric sciences
Year 2015
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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.

Systematic review

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Journal Schizophrenia bulletin
Year 2015
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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.