OPUS
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Opus‐project: differences in treatment outcome of a randomised controlled trial of integrated psychiatric treatment of first‐episode psychotic patients.

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Journal Proceedings of the 11th World Congress of Psychiatry
Year 1999
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Opus ‐ project : a randomised controlled trial of first episode psychotic patients better compliance

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Journal Proceedings of the 2nd International Conference on Early Psychosis
Year 2000
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Early detection and assertive community treatment of young psychotics: the Opus Study Rationale and design of the trial.

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Journal Social psychiatry and psychiatric epidemiology
Year 2000
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BACKGROUND: Recent research indicates that early detection of young persons suffering from psychosis and subsequent intensive intervention enhances treatment response and prognosis, but the data are only preliminary and suggestive. METHOD: We present the rationale and design of the largest study to date to evaluate two major issues in the field of secondary prevention: (1) Does education and intensified collaboration with general practice, social services etc. reduce the duration of untreated psychosis? and (2) Can modified assertive community treatment improve the course and outcome in young persons suffering from psychosis as compared to treatment in community mental health centres? The article aims additionally to put the study in context and assist in designing future studies. RESULTS: Preliminary experiences are described. The findings of the first 312 patients show that modified assertive community treatment results in patients adhering to treatment significantly better than standard treatment in community mental health centres. CONCLUSION: The surge of interest in preventively oriented detection and treatment models for untreated psychosis in young people calls for research programmes and evidence. The obstacles to this are manifold. The initial findings of the OPUS study suggest, however, that better adherence to treatment is possible.

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OPUS study: suicidal behaviour, suicidal ideation and hopelessness among patients with first-episode psychosis. One-year follow-up of a randomised controlled trial.

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Journal The British journal of psychiatry. Supplement
Year 2002
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BACKGROUND: Patients with first-episode psychosis comprise a high-risk group in terms of suicide. AIMS: To identify predictive factors for suicidal behaviour and to examine the effect of integrated treatment on suicidal behaviour and hopelessness. METHOD: A total of 341 patients with a first-episode schizophrenia-spectrum disorder were randomised to integrated treatment or treatment as usual. RESULTS: During the 1-year follow-up period, 11% attempted suicide. This was associated with female gender, hopelessness, hallucinations and suicide attempt reported at baseline, with the two latter variables being the only significant ones in the final multivariate model. The integrated treatment reduced hopelessness. CONCLUSIONS: Hallucinations and suicide attempt before inclusion in the study were the most significant predictors of suicide attempt in the follow-up period.

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Opus‐project: a randomised controlled trial of integrated psychiatric treatment in first‐episode psychosis ‐ clinical outcome improved.

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Journal Proceeding of the 3rd International Conference on Early Psychosis
Year 2002
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Integrated treatment ameliorates negative symptoms in first episode psychosis--results from the Danish OPUS trial.

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Journal Schizophrenia research
Year 2005
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PURPOSE: To investigate the effect of integrated treatment on negative, psychotic and disorganised symptoms in patients with first episode psychosis. METHOD: A RCT comparing integrated treatment (IT) with standard treatment (ST) was conducted, including 547 patients, aged 18-45, diagnosed with schizophrenia spectrum disorders. All patients were assessed with SCAN, SAPS and SANS at entry and after 1 and 2 years. The IT consisted of assertive community treatment, multifamily groups, psycho-education and social skills training, and the caseload was 1:10 compared with 1:25 in ST. Since attrition was considerable, a mixed model analysis with repeated measurements was used to examine the possible effects of IT statistically. RESULTS: IT reduced both negative and positive symptoms significantly better than ST. Most marked were the results from the negative dimension, where all five global scores from SANS had a significantly better reduction in IT. Sub-analyses did not single out any one element in the integrated treatment that could explain this result. CONCLUSION: Integrated treatment significantly reduced both negative and psychotic symptoms, assumably due to the different psychosocial treatment elements that were provided in the IT. The results indicate that the integrated approach is crucial, since, most likely, many aspects of the integrated treatment have contributed to the reduction of symptoms.

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Improving 1-year outcome in first-episode psychosis: OPUS trial.

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Journal The British journal of psychiatry. Supplement
Year 2005
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BACKGROUND: Because early illness course and outcome may affect the long-term outcome of schizophrenia-spectrum disorders, it is especially important to address poor outcome in this early critical period. AIMS: To evaluate whether integrated treatment compared with standard treatment reduced the proportion of patients with poor clinical and social outcome after 1 year. METHOD: A total of 547 patients with first-episode psychosis were included in the study, 275 randomly assigned to integrated treatment and 272 to standard treatment. Measures assessed psychotic symptoms and social functioning. RESULTS: There was a significant beneficial effect of integrated treatment v. standard treatment on "any poor outcome". Integrated treatment had a significantly better effect on "any poor outcome" in patients with schizophrenia compared with patients in standard treatment. CONCLUSIONS: The integrated treatment significantly reduced the proportion of patients with poor clinical and social outcome compared with standard treatment.

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Integrated treatment of first-episode psychosis: effect of treatment on family burden: OPUS trial.

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Journal The British journal of psychiatry. Supplement
Year 2005
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BACKGROUND: The families of patients with first-episode psychosis often play a major role in care and often experience lack of support. AIMS: To determine the effect of integrated treatment v. standard treatment on subjective burden of illness, expressed emotion (EE), knowledge of illness and satisfaction with treatment in key relatives of patients with a first episode of schizophrenia-spectrum disorder. METHOD: Patients with ICD-10 schizophrenia-spectrum disorders (first episode) were randomly assigned to integrated treatment or to standard treatment. Integrated treatment consisted of assertive community treatment, psychoeducational multi-family groups and social skills training. Key relatives were assessed with the Social Behaviour Assessment Schedule (SBAS, burden of illness), the 5-min speech sample (EE), and a multiple choice questionnaire at entry and after 1 year. RESULTS: Relatives in integrated treatment felt less burdened and were significantly more satisfied with treatment than relatives in standard treatment. There were no significant effects of intervention groups on knowledge of illness and EE. CONCLUSIONS: The integrated treatment reduced family burden of illness and improved satisfaction with treatment.

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A randomised multicentre trial of integrated versus standard treatment for patients with a first episode of psychotic illness.

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Journal BMJ (Clinical research ed.)
Year 2005
Links Pubmed DOI PubMed Central
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OBJECTIVES: To evaluate the effects of integrated treatment for patients with a first episode of psychotic illness. DESIGN: Randomised clinical trial. SETTING: Copenhagen Hospital Corporation and Psychiatric Hospital Aarhus, Denmark. PARTICIPANTS: 547 patients with first episode of schizophrenia spectrum disorder. INTERVENTIONS: Integrated treatment and standard treatment. The integrated treatment lasted for two years and consisted of assertive community treatment with programmes for family involvement and social skills training. Standard treatment offered contact with a community mental health centre. MAIN OUTCOME MEASURES: Psychotic and negative symptoms (each scored from 0 to a maximum of 5) at one and two years' follow-up. RESULTS: At one year's follow-up, psychotic symptoms changed favourably to a mean of 1.09 (standard deviation 1.27) with an estimated mean difference between groups of -0.31 (95% confidence interval -0.55 to -0.07, P = 0.02) in favour of integrated treatment. Negative symptoms changed favourably with an estimated difference between groups of -0.36 (-0.54 to -0.17, P < 0.001) in favour of integrated treatment. At two years' follow-up the estimated mean difference between groups in psychotic symptoms was -0.32 (-0.58 to -0.06, P = 0.02) and in negative symptoms was -0.45 (-0.67 to -0.22, P < 0.001), both in favour of integrated treatment. Patients who received integrated treatment had significantly less comorbid substance misuse, better adherence to treatment, and more satisfaction with treatment. CONCLUSION: Integrated treatment improved clinical outcome and adherence to treatment. The improvement in clinical outcome was consistent at one year and two year follow-ups.

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The opus trial: a randomised multi‐centre trial of integrated versus standard treatment for 547 first‐episode psychotic patients.

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Journal Schizophrenia Bulletin
Year 2005
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Duration of untreated psychosis predicts psychotic symptoms but not negative symptoms.

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Journal Schizophrenia Bulletin
Year 2005
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[OPUS: a randomised multicenter trial of integrated versus standard treatment for patients with a first-episode psychosis--secondary publication].

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Journal Ugeskrift for laeger
Year 2006
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A total of 547 patients with first-episode psychosis were included in a randomised clinical trial comparing integrated treatment with standard treatment. The integrated treatment consisted of assertive community treatment with programmes for family involvement and social skills training. Patients in integrated treatment had significantly fewer psychotic and negative symptoms, less comorbid substance abuse, better adherence to treatment and more satisfaction with treatment at one-year and two-year follow-ups.

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Substance abuse in first‐episode schizophrenia‐spectrum disorders

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Journal Schizophrenia Research
Year 2006
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Social network among young adults with first-episode schizophrenia spectrum disorders: results from the Danish OPUS trial.

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Journal Social psychiatry and psychiatric epidemiology
Year 2006
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BACKGROUND: Social network has considerable impact on physical and mental health. Patients experiencing first-episode psychosis early in adult life may experience severe problems concerning development and maintenance of their social network. METHODS: A total of 547 first-episode psychotic patients (18-45) were randomised to standard or integrated treatment, (ACT, social skills training and family intervention), and followed up at 2 years. RESULTS: Service use or psychotic symptom score did not influence the social network size, measured after the first 2 years of treatment. Small network size was associated with long duration of untreated psychosis (DUP), poor premorbid adjustment, male gender and severe negative symptoms. The number of friends at 2-year follow-up was predicted by age, A-level status, negative symptoms and number of friends at entry, while the determinants for number of family contacts were age, gender, disorganised dimension and family contacts at entry. CONCLUSIONS: Premorbid functioning, network size at entry and DUP is closely related to small social network size. The integrated psychosocial treatment programme was not sufficient to address this problem.

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Transition rates from schizotypal disorder to psychotic disorder for first-contact patients included in the OPUS trial. A randomized clinical trial of integrated treatment and standard treatment.

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Journal Schizophrenia research
Year 2006
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BACKGROUND: Only a few randomized clinical trials have tested the effect on transition rates of intervention programs for patients with sub-threshold psychosis-like symptoms. AIM: To examine whether integrated treatment reduced transition to psychosis for first-contact patients diagnosed with schizotypal disorder. METHODS: Seventy-nine patients were randomized to integrated treatment or standard treatment. Survival analysis with multivariate Cox-regression was used to identify factors determinant for transition to psychotic disorder. RESULTS: In the multivariate model, male gender increased risk for transition to psychotic disorder (relative risk=4.47, (confidence interval 1.30-15.33)), while integrated treatment reduced the risk (relative risk=0.36 (confidence interval 0.16-0.85)). At two-year follow-up, the proportion diagnosed with a psychotic disorder was 25.0% for patients randomized to integrated treatment compared to 48.3% for patients randomized to standard treatment. CONCLUSION: Integrated treatment postponed or inhibited onset of psychosis in significantly more cases than standard treatment.

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The OPUS trial: results from the five‐year follow‐up

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Journal Schizophrenia Research
Year 2006
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Intensive treatment models and coercion.

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Journal Nordic journal of psychiatry
Year 2007
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Little evidence exists concerning the optimal treatment for patients with first-episode schizophrenia-spectrum disorders and the effect on traditional outcomes. The aim was to investigate whether optimal treatment models have an effect on the level of use of coercion and on traditional outcomes. Hospital-based Rehabilitation, an intensified inpatient treatment model, Integrated Treatment, an intensified model of Assertive Community Treatment, and standard treatment were compared for patients with first-episode schizophrenia-spectrum disorders. Ninety-four patients with first-episode schizophrenia-spectrum disorders estimated to benefit from long-term hospitalization were included consecutively from the Copenhagen OPUS-trial and randomized to the three treatment models. At 1-year follow-up, Hospital-based Rehabilitation and Integrated Treatment had better scores on symptoms in the negative dimension and on client satisfaction. Integrated Treatment had fewer bed-days, more patients living in non-supervised accommodation, and better score on quality of life. No differences were found as to the use of coercion. This study adds to the evidence that intensified treatment models are superior to standard treatment. A higher number of bed-days in Hospital-based Rehabilitation did not influence the effect on the outcomes measured.

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Substance abuse and first-episode schizophrenia-spectrum disorders. The Danish OPUS trial.

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Journal Early intervention in psychiatry
Year 2007
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AIM: To evaluate whether integrated treatment (given by OPUS), in comparison with standard treatment, significantly reduced the number of patients with substance abuse and improved clinical and social outcome in the group of substance abusers after 2 years. METHODS: A total of 547 patients with first-episode schizophrenia-spectrum disorders were included in the study, 275 randomly assigned to OPUS treatment and 272 to standard treatment. OPUS treatment consisted of assertive community treatment with family involvement and social skills training. Standard treatment offered contact with a community mental health centre. Main outcome measure was reduction in comorbid substance abuse. RESULTS: At 2-year follow up, 42 (17.3%) patients from OPUS and 40 (20.7%) patients from standard treatment met criteria for substance abuse (odds ratio=0.5, 95% confidence interval 0.3-1.0). OPUS treatment compared with standard treatment significantly reduced negative and disorganized symptoms in the substance abuser group. Patients with substance abuse in the OPUS treatment spent significantly fewer days in hospital during the 2-year period than patients given standard treatment (109 days vs. 167 days) and adhered to treatment significantly more often. CONCLUSIONS: Results from this trial indicate that integrated treatment given by OPUS reduced substance abuse and improved clinical outcome in the substance abuser group. Supplementing the OPUS treatment with therapeutic programmes for patients with a comorbid substance abuse would probably further improve outcome.

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The association between pre-morbid adjustment, duration of untreated psychosis and outcome in first-episode psychosis.

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Journal Psychological medicine
Year 2008
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BACKGROUND: The association between the duration of untreated psychosis (DUP) and outcome of schizophrenia may be confounded by other factors such as poor pre-morbid adjustment. The aim of the present study was to examine the independent contributions of DUP and of pre-morbid adjustment to the clinical and social outcomes of schizophrenia. METHOD: A longitudinal, prospective, 2-year follow-up study of 423 patients with first-episode schizophrenia-spectrum psychosis was conducted. Patients were comprehensively assessed at entry, 1-year and 2-year follow-up. At entry, DUP was measured by IRAOS (an instrument for the assessment of onset and early course of schizophrenia) and pre-morbid adjustment was measured by the Pre-morbid Adjustment Scale (PAS) as 'pre-morbid social adaptation' and 'pre-morbid school adaptation'. Outcome measures included the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), the Social Network Schedule and social information. Multiple linear regression models were used for data analysis. RESULTS: The median DUP was 48 weeks, which is long compared to other studies. Longer DUP was independently associated with more psychotic symptoms at entry, 1-year and 2-year follow-up. Poorer pre-morbid social adaptation was independently associated with more negative symptoms and smaller social network at entry and 1-year follow-up. Poorer pre-morbid school adaptation was independently associated with poor vocational outcome at 1-year and 2-year follow-up. CONCLUSIONS: Longer DUP is associated with poorer 2-year outcome of psychosis in schizophrenia-spectrum disorders, when pre-morbid functioning and other prognostic factors are controlled for. Impaired pre-morbid development is independently associated with more negative symptoms and poorer social outcome.

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Five-year follow-up of a randomized multicenter trial of intensive early intervention vs standard treatment for patients with a first episode of psychotic illness: the OPUS trial.

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Journal Archives of general psychiatry
Year 2008
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CONTEXT: Intensive early treatment for first-episode psychosis has been shown to be effective. It is unknown if the positive effects are sustained for 5 years. OBJECTIVE: To determine the long-term effects of an intensive early-intervention program (OPUS) for first-episode psychotic patients. DESIGN: Single-blinded, randomized, controlled clinical trial of 2 years of an intensive early-intervention program vs standard treatment. Follow-up periods were 2 and 5 years. SETTING: Copenhagen Hospital Corporation and Psychiatric Hospital, Aarhus, Denmark. Patients A total of 547 patients with a first episode of psychosis. Of these, 369 patients were participating in a 2-year follow-up, and 301 were participating in a 5-year follow-up. A total of 547 patients were followed for 5 years. INTERVENTIONS: Two years of an intensive early-intervention program vs standard treatment. The intensive early-intervention treatment consisted of assertive community treatment, family involvement, and social skills training. Standard treatment offered contact with a community mental health center. MAIN OUTCOME MEASURES: Psychotic and negative symptoms were recorded. Secondary outcome measures were use of services and social functioning. RESULTS: Analysis was based on the principles of intention-to-treat. Assessment was blinded for previous treatment allocation. At the 5-year follow-up, the effect of treatment seen after 2 years (psychotic dimension odds ratio [OR], -0.32; 95% confidence interval [CI], -0.58 to -0.06; P = .02; negative dimension OR, -0.45; 95% CI, -0.67 to -0.22; P = .001) had equalized between the treatment groups. A significantly smaller percentage of patients from the experimental group were living in supported housing (4% vs 10%, respectively; OR, 2.3; 95% CI, 1.1-4.8; P = .02) and were hospitalized fewer days (mean, 149 vs 193 days; mean difference, 44 days; 95% CI, 0.15-88.12; P = .05) during the 5-year period. CONCLUSIONS: The intensive early-intervention program improved clinical outcome after 2 years, but the effects were not sustainable up to 5 years later. Secondary outcome measures showed differences in the proportion of patients living in supported housing and days in hospital at the 5-year follow-up in favor of the intensive early-intervention program.

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Effect of integrated treatment on the use of coercive measures in first-episode schizophrenia-spectrum disorder. A randomized clinical trial.

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Journal International journal of law and psychiatry
Year 2008
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Abstract: The effect of integrated treatment on the use of coercive measures in first-episode schizophrenia-spectrum disorder in Denmark is not known. A total of 328 patients were randomly assigned to integrated treatment (167 patients) or standard treatment (161 patients). Integrated treatment consisted of assertive community treatment, psycho-educational multi-family groups, and social skills training. Data on coercion were extracted from the register from the National Board of Health, and data on continuity from medical records. Even though the level of continuity seemed higher in integrated treatment, this did not reduce the use of coercive measures compared to the use in standard treatment.

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Course of illness in a sample of 265 patients with first-episode psychosis-Five-year follow-up of the Danish OPUS trial

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Journal Schizophrenia research
Year 2009
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There is an ongoing debate as to whether psychosis is a progressively deteriorating illness or one of progressive amelioration. This paper aims at investigating the rate of recovery and institutionalization and predicting a continuous illness course in a descriptive prospective study of a sub-sample of the OPUS trial of 265 first-episode psychotic patients after five years. Recovery, defined as no psychotic or negative symptoms, living independently, GAF (f) > 59, working or studying, was reached for 18% after five years, whereas 13% were institutionalized either at hospital or supported housing after five years. Male gender (OR 1.9, 95% CI 1.06 to 3.23), premorbid social functioning (OR 1.2, 95% CI 1.01 to 1.33), psychotic symptoms (OR 1.3, 95% CI 1.07 to 1.66), and negative symptoms (OR 1.3, 95% CI 1.01 to 1.67) were found to predict a continuous illness course at five-year follow-up. Rates of recovery and institutionalization contradict the assumption that the illness deteriorates progressively, since no changes in the rates are seen from two to five years. © 2008 Elsevier B.V. All rights reserved.

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The quality of life among first-episode psychotic patients in the opus trial

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Journal Schizophrenia research
Year 2010
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Background: From an 'objective' perspective, treatment of first-episode psychosis has improved in many ways with the development of specialised early and intensive team-based treatment like e.g. the 'OPUS' treatment. However, the patients' perspective is also important and was investigated in the 'OPUS' study by analysing data concerning quality of life. Aim: We aimed to investigate the 'quality of life from patients' perspective' among a cohort of young adults with a first-episode psychosis at the time of treatment initiation and after two years. Especially, we were interested in analysing if there were any significant effects on the subjective quality of life of receiving an intensive psychosocial assertive community treatment called 'OPUS' compared to standard treatment (ST). Method: This study is part of the Danish 'OPUS' trial, a randomised controlled trial (RCT) comparing 'treatment as usual' (standard treatment, ST) with 'OPUS' treatment. The Lancashire Quality of Life Profile (LQoLP), which is a combined objective and subjective instrument, was administered at baseline and after two years of treatment, N = 280. Results: The intensive 'OPUS' treatment did not affect the quality of life measured by Lancashire QoLP in a significantly different way from the standard treatment (ST). There were no significant differences in quality of life between the ST group and the OPUS group concerning the 9 life domains. Quality of life correlated with psychopathology (both psychotic and negative symptoms) to a minor extent and more strongly with the affective balance and level of self-esteem. © 2009 Elsevier B.V. All rights reserved.

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Deinstitutionalization revisited: a 5-year follow-up of a randomized clinical trial of hospital-based rehabilitation versus specialized assertive intervention (OPUS) versus standard treatment for patients with first-episode schizophrenia spectrum disorders

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Journal Psychological medicine
Year 2010
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BACKGROUND: The effects of hospital-based rehabilitation including weekly supportive psychodynamic therapy compared with specialized assertive intervention and standard treatment has not previously been investigated in first-episode psychosis. The aim of the study was to examine long-term effect on use of institutional care of different intensive interventions for patients with first-episode schizophrenia spectrum disorder on use of psychiatric bed days and days in supported housing. METHOD: A total of 94 severely ill patients with first-episode schizophrenia spectrum disorders were included in a special part of the Copenhagen OPUS trial and randomized to either the specialized assertive intervention program (OPUS), standard treatment or hospital-based rehabilitation. RESULTS: It was a stable pattern that patients randomized to hospital-based rehabilitation spent more days in psychiatric wards and in supported housing throughout the 5-year follow-up period compared with the two other groups. Patients in OPUS treatment spent significantly fewer days in psychiatric wards and supported housing in the first 3 years compared with patients in hospital-based rehabilitation. Due to attrition and small sample size, differences in level of psychotic and negative symptoms at 5-year follow-up could not be evaluated. CONCLUSIONS: The study indicates that hospital-based rehabilitation together with weekly supportive psychodynamic therapy was associated with a continued increased use of psychiatric bed days and days in supported housing. The data cannot justify using hospital-based rehabilitation in first-episode psychosis.

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Reduction of crime in first-onset psychosis: a secondary analysis of the OPUS randomized trial.

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Journal The Journal of clinical psychiatry
Year 2013
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OBJECTIVE: Violence and criminality are adverse outcomes for some persons who develop psychotic illnesses. The extent to which treatment can reduce offending has rarely been studied. The aim of this study was to evaluate whether assertive specialized treatment would reduce the rate of crime in patients with a first episode of psychotic illness. METHOD: From January 1998 to December 2000, a total of 547 patients aged 18-45 years with a first episode of schizophrenia spectrum disorder (ICD-10 diagnostic code within F2) were randomized to assertive specialized treatment or standard treatment in an outpatient setting. In the current secondary analysis of the data, levels of criminality during the 2-year treatment period and the 3 years following were assessed using official records from Danish registers. Main outcome measures were any offending and violent offending. RESULTS: No significant reduction in violent offending or any offending was found in the assertive specialized treatment group (adjusted hazard ratio = 1.06; 95% CI, 0.72-1.56) compared with the control group. Prevalence of offending was low and had often commenced prior to inclusion in the trial. CONCLUSIONS: While assertive specialized treatment has shown good treatment effects, it had no impact on rates of offending, thereby calling into question the potential efficacy of universally applied improvements in outpatient services with respect to reducing crime and violence. More specific interventions that address criminogenic needs in a more narrowly defined group of high-risk patients may be considered.

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Cost-effectiveness of early intervention in first-episode psychosis: economic evaluation of a randomised controlled trial (the OPUS study).

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Journal The British journal of psychiatry : the journal of mental science
Year 2013
Links Pubmed Health Technology Assessment (HTA) DOI crd.york.ac.uk
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BACKGROUND: Information about the cost-effectiveness of early intervention programmes for first-episode psychosis is limited. AIMS: To evaluate the cost-effectiveness of an intensive early-intervention programme (called OPUS) (trial registration NCT00157313) consisting of enriched assertive community treatment, psychoeducational family treatment and social skills training for individuals with first-episode psychosis compared with standard treatment. METHOD: An incremental cost-effectiveness analysis of a randomised controlled trial, adopting a public sector perspective was undertaken. RESULTS: The mean total costs of OPUS over 5 years (€123,683, s.e. = 8970) were not significantly different from that of standard treatment (€148,751, s.e. = 13073). At 2-year follow-up the mean Global Assessment of Functioning (GAF) score in the OPUS group (55.16, s.d. = 15.15) was significantly higher than in standard treatment group (51.13, s.d. = 15.92). However, the mean GAF did not differ significantly between the groups at 5-year follow-up (55.35 (s.d. = 18.28) and 54.16 (s.d. = 18.41), respectively). Cost-effectiveness planes based on non-parametric bootstrapping showed that OPUS was less costly and more effective in 70% of the replications. For a willingness-to-pay up to €50,000 the probability that OPUS was cost-effective was more than 80%. CONCLUSIONS: The incremental cost-effectiveness analysis showed that there was a high probability of OPUS being cost-effective compared with standard treatment.

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Gender differences in first-episode psychosis at 5-year follow-up--two different courses of disease? Results from the OPUS study at 5-year follow-up.

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Journal European psychiatry : the journal of the Association of European Psychiatrists
Year 2014
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OBJECTIVE: Gender differences in psychosis have been investigated, and the results have contributed to a better understanding of the disease, but many questions are unanswered. In clinical terms, women and men with psychosis differ in terms of access to social support, tendency of substance abuse, level of functioning and symptom patterns. We aimed to investigate how gender differences at onset of psychosis develop during the first 5years of treatment. METHOD: A total of 578 patients with a first-episode psychosis in the schizophrenia spectrum were included in the Danish OPUS trial--a randomized clinical trial comparing 2 years of intensive early-intervention programme with standard treatment. All patients were assessed with validated instruments at inclusion, and after 2 and 5 years. Data were analysed for significant gender differences. RESULTS: Males have significantly higher levels of negative symptoms at all times, and are more likely to live alone and suffer from substance abuse. Females reach higher levels of social functioning at follow-up, and show a greater tendency to be employed or in education than males. Markedly more women than men live with children. More women than men reach a state of recovery and are more compliant with medication. CONCLUSION: There are significant gender differences at 2- and 5-year follow-up in this large cohort of first-episode psychotic patients. Males and females show different symptomatology and different levels of social functioning.

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Long-term trajectories of positive and negative symptoms in first episode psychosis: A 10year follow-up study in the OPUS cohort.

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Journal Schizophrenia research
Year 2015
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OBJECTIVE: Knowledge about course of illness can help clinicians to develop effective interventions and improve treatment outcomes. The goal of this study was to construct positive and negative symptom trajectories based on structured clinical assessments collected over 10years within a cohort of people with first episode psychosis. METHOD: A cohort of 496 people with first episode psychosis (ICD-10, F20-28) originally recruited for the OPUS study (1998-2000) and treated in community psychiatric services were rated on clinical symptoms at 5 different occasions across ten years. Psychopathology was assessed using the Scales for Assessment of Positive and Negative Symptoms. Symptom trajectories were constructed using Latent Class Analysis. RESULTS: Five distinct trajectories were identified for positive symptoms (response - 47%, delayed response - 12%, relapse - 15%, non-response - 13% and episodic response - 13%). Four distinct trajectories were identified for negative symptoms (response - 28%, delayed response - 19%, relapse - 26% and non-response - 27%). Multivariable regression analysis of baseline characteristics identified that longer duration of untreated psychosis (OR 1.27-1.47, p<0.05) and substance abuse (OR 3.47-5.90, p<0.01) were associated with poorer positive symptom trajectories (higher levels of psychotic symptoms) while poor social functioning (OR 1.34-5.55, p<0.05), disorganized symptoms (OR 2.01-2.38, p<0.05) and schizophrenia diagnosis (OR 5.70-8.86, p<0.05) were associated with poorer negative symptom trajectories (higher levels of negative symptoms). A proportion of people displayed significant changes in symptoms several years after diagnosis. CONCLUSIONS: Trajectories of illness for positive and negative symptoms were heterogeneous among people with first episode psychosis. Positive symptoms showed a general pattern of reduction and stabilization over time while negative symptoms typically showed less variation over the ten years. Results have implications for the focus, timing and length of interventions in first episode psychosis.

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Ten-year follow-up of the OPUS specialized early intervention trial for patients with a first episode of psychosis.

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Journal Schizophrenia bulletin
Year 2015
Links Pubmed DOI PubMed Central
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INTRODUCTION: Specialized early intervention programs such as The Danish OPUS treatment are efficient in treating patients with a first episode of psychosis (FEP) at least after 2 and 5 years. Few studies have examined long-term outcomes of these interventions. AIM: To examine the effect of 2 years of OPUS vs treatment as usual (TAU) within an FEP cohort, 10 years after inclusion into the OPUS trial. METHODS: From 1998 to 2000, participants were randomized to OPUS or TAU. Ten years later, we conducted comprehensive interviews and performed register-based follow-up on all participants in national Danish registers. We analyzed participants according to the intention-to-treat principle. RESULTS: Of the 547 participants included in the study, 347 (63.4%) took part in this follow-up. While there was evidence of a differential 10-year course in the development of negative symptoms, psychiatric bed days, and possibly psychotic symptoms in favor of OPUS treatment, differences were driven by effects at earlier follow-ups and had diminished over time. Statistically significant differences in the course of use of supported housing were present even after 8-10 years. There were no differences between OPUS and TAU regarding income, work-related outcomes, or marital status. CONCLUSION: Most of the positive short-term effects of the OPUS intervention had diminished or vanished at this long-term follow-up. We observed a clear tendency that OPUS treatment leads to fewer days in supported housing. There is a need for further studies investigating if extending the intervention will improve outcomes more markedly at long-term follow-ups.

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From research to practice: how OPUS treatment was accepted and implemented throughout Denmark.

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Journal Early intervention in psychiatry
Year 2015
Links Pubmed DOI www.epistemonikos.org
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BACKGROUND: The early phases of psychosis have been hypothesized to constitute a critical period, a window of opportunity. At the same time, the early phases of psychosis are associated with increased risk of unwanted outcome, such as suicidal behaviour and social isolation. This was the background for the emergence of early intervention services, and in Denmark, the OPUS trial was initiated as part of that process. METHODS: Modified assertive community treatment, together with family involvement and social skills training, constituted the core elements in the original programme. A total of 547 patients with first-episode psychosis were included in the trial. RESULTS: To summarize briefly the results of the OPUS trial: the OPUS treatment was superior to standard treatment in reducing psychotic and negative symptoms and substance abuse, in increasing user satisfaction and adherence to treatment, and in reducing use of bed days and days in supported housing. Moreover, relatives included in the OPUS treatment were less strained and had a higher level of knowledge about schizophrenia and higher user satisfaction. DISCUSSION: The OPUS treatment was implemented throughout Denmark. Training courses were developed and manuals and books were published. Regional health authorities had access to national grants for implementing early intervention services; as a result, OPUS teams were disseminated throughout the country. The content of the treatment is now further developed, and new elements are being tried out - such as individual placement and support, lifestyle changes, cognitive remediation, specialized treatment for substance abuse and different kinds of user involvement.

Primary study

Unclassified

Trajectories of suicidal ideation in patients with first-episode psychosis: secondary analysis of data from the OPUS trial.

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Journal The lancet. Psychiatry
Year 2016
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BACKGROUND: Heterogeneity in suicidal ideation over time in patients with first-episode psychosis is expected, but prototypical trajectories of this have not yet been established. We aimed to identify trajectories of suicidal ideation over a 3-year period and to examine how these trajectories relate to subsequent suicidality. METHODS: We used longitudinal data from the prospective 10-year follow-up OPUS trial of young Danish patients with first-episode psychosis. Participants were recruited between January, 1998, and December, 2000, from all inpatient and outpatient mental health services in Copenhagen and Aarhus County, were aged between 18 and 45 years, and had a diagnosis in the schizophrenia spectrum. Randomisation was done by a computer-generated randomisation list, stratified in alternating blocks for five centres. In Aarhus, a secretary drew lots when the researcher phoned her. Patients were randomly assigned to a treatment group (modified assertive community treatment) or a control group (standard treatment at community mental health centres) and assessed at treatment initiation, and after 1, 2, 5, and 10 years. We included all patients' data on suicidal ideation from the first three assessments in a latent growth mixture modelling analysis to empirically identify trajectories of suicidal ideation. Multivariable logistic regression analyses were applied to estimate associations between trajectories and subsequent suicidality. This trial is registered with ClinicalTrials.gov, number NCT00157313. FINDINGS: Three trajectories for suicidal ideation were identified in 521 patients. 317 of 521 members (61%) of the largest trajectory, low-decreasing, consisted of patients who initially reported suicidal ideation once-to-a-few-times in the past year followed by a decrease in suicidal ideation. 172 of 521 (33%) members of the frequent-stable trajectory reported suicidal ideation sometimes-to-frequently at the first assessment and remained stable over time. Finally, 32 of 521 (6%) members of the frequent-increasing trajectory reported frequent suicidal ideation initially followed by worsening. Compared with the low-decreasing class, the risk of persistent suicidal ideation was higher for patients in the frequent-stable and frequent-increasing classes at 5 years (Odds ratio=4·5, 95% CI 2·50-8·02 and 4·7, 1·55-14·24 respectively) and at 10 years (4·2, 2·42-7·13 and 3·2, 1·20-8·70 respectively). Also the risk of suicide attempt at 5 years was higher for patients in the frequent-stable (2·8, 1·07-7·43) and frequent-increasing classes (6·6, 1·69-25·54) compared with the low-decreasing class. There was no difference in suicide rate at 5 or 10 years between trajectories. INTERPRETATION: Because up to 40% of patients experienced frequent suicidal ideations that persisted or increased during the first years of treatment, our findings warrant special focus on suicidal issues as an integral part of treatment along with treatment to target psychotic symptoms. FUNDING: The Danish Council for Independent Research (Medical Sciences), Trygfonden, The Mental Health Services of the Capital Region of Denmark, The Danish Ministry of Health, The Danish Ministry of Social Affairs, the Psychiatry and Social Service Department in Central Denmark Region, and The Lundbeck Foundation.

Primary study

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Predictors and longitudinal course of cognitive functioning in schizophrenia spectrum disorders, 10years after baseline: The OPUS study.

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Journal Schizophrenia research
Year 2016
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BACKGROUND: Identifying baseline predictors of the long-term course of cognitive functioning in schizophrenia spectrum disorders is important because of associations between cognitive functioning (CF) and functional outcome. Determining whether CF remains stable or change during the course of illness is another matter of interest. METHODS: Participants from The Danish OPUS Trial, aged 18-45years, with a baseline ICD-10 schizophrenia spectrum diagnosis, were assessed on psychopathology, social and vocational functioning at baseline, and cognitive functioning 5 (N=298) and 10years (N=322) after baseline. Uni- and multi-variable regression analyses of potential baseline predictors of 10-year CF were performed. Also, changes in CF and symptomatology between 5 and 10years of follow-up were assessed. FINDINGS: Baseline predictors of impaired CF after 10years included male gender, unemployment, poor premorbid achievement and later age of onset. Having finished high school and receiving early intervention treatment was associated with better CF. Age, growing up with both parents, number of family and friends, primary caregivers education, premorbid social function, negative symptoms, GAF (symptoms, function) and substance abuse, were associated with CF in univariable analyses. Non-participants generally suffered from more severe dysfunction. Longitudinally, amelioration in negative symptoms was associated with improved speed of processing and executive functions. Symptom scores generally improved with time, while scores for all cognitive tests remained stable. CONCLUSION: The current study identifies several robust associations between baseline characteristics and 10-year cognitive outcome. Several other variables were univariably associated with 10-year cognitive outcome. Also, we found evidence for stability of CF over time.

Primary study

Unclassified

Antipsychotic medication and remission of psychotic symptoms 10years after a first-episode psychosis.

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Journal Schizophrenia research
Year 2017
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BACKGROUND: Several national guidelines recommend continuous use of antipsychotic medication after a psychotic episode in order to minimize the risk of relapse. However some studies have identified a subgroup of patients who obtain remission of psychotic symptoms while not being on antipsychotic medication for a period of time. This study investigated the long-term outcome and characteristics of patients in remission of psychotic symptoms with no use of antipsychotic medication at the 10-year follow-up. METHODS: The study was a cohort study including 496 patients diagnosed with schizophrenia spectrum disorders (ICD 10: F20 and F22-29). Patients were included in the Danish OPUS Trial and followed up 10years after inclusion, where patient data was collected on socio-demographic factors, psychopathology, level of functioning and medication. FINDINGS: 61% of the patients from the original cohort attended the 10-year follow up and 30% of these had remission of psychotic symptoms at the time of the 10-year follow up with no current use of antipsychotic medication. This outcome was associated with female gender, high GAF-F score, participation in the labour market and absence of substance abuse. CONCLUSION: Our results describe a subgroup of patients who obtained remission while not being on antipsychotic medication at the 10-year follow-up. The finding calls for further investigation on a more individualized approach to long-term treatment with antipsychotic medication.