Per Jørgensen

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

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.

Gender differences in young adults with first-episode schizophrenia spectrum disorders at baseline in the danish opus study

Gender differences in age at first onset, duration of untreated psychosis, psychopathology, social functioning, and self-esteem were investigated in a group of 578 young adults with a first-episode schizophrenia spectrum disorder. The mean age at first-onset of symptoms, age at first contact, and duration of untreated psychosis were similar for men and women. Men had more severe negative symptoms, poorer premorbid functioning, and poorer social networks, whereas women had more severe hallucinations. More men than women were substance abusers, were unemployed, and lived alone. Women had poorer self-esteem than men, in spite of better scores in functioning. Premorbid social adjustment was significantly related to the level of negative symptoms and number of friends. Conclusion is that men and women with first-episode psychosis showed different psychopathological characteristics and different social functioning, which cannot be explained by older age of onset for women. Women make more suicide attempts and experience lower self-esteem in spite of better social functioning.

Integrated treatment ameliorates negative symptoms in first episode psychosis—results from the Danish OPUS trial

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.

Suicidal behaviour and mortality in first-episode psychosis: the OPUS trial

BACKGROUND Those with first-episode psychosis are at high-risk of suicide. AIMS To identify predictive factors for suicidal thoughts, plans and attempts, and to investigate the rate of suicides and other deaths during the 5 years after first diagnosis and initiation of treatment. METHOD A longitudinal, prospective, 5-year follow-up study of 547 individuals with first-episode schizophrenia spectrum psychosis. Individuals presenting for their first treatment in mental health services in two circumscribed urban areas in Denmark were included in a randomised controlled trial of integrated v. standard treatment. All participants were followed in the Danish Cause of Death Register for 5 years. Suicidal behaviour and clinical and social status were assessed using validated interviews and rating scales at entry, and at 1- and 2-year follow-ups. RESULTS Sixteen participants died during the follow-up. We found a strong association between suicidal thoughts, plans and previous attempts, depressive and psychotic symptoms and young age, and with suicidal plans and attempts at 1- and 2-year follow-up. CONCLUSIONS In this first-episode cohort depressive and psychotic symptoms, especially hallucinations, predicted suicidal plans and attempts, and persistent suicidal behaviour and ideation were associated with high risk of attempted suicide.

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

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.

Predictors of recovery from psychosis Analyses of clinical and social factors associated with recovery among patients with first-episode psychosis after 5 years

INTRODUCTION This paper aims to investigate the predictors of good outcome after first-episode non-affective psychosis and the clinical and social trajectories of those that recover. METHODS A cohort of 255 patients with first-episode non-affective psychosis was interviewed 5 years after first diagnosis and treatment. Recovery was defined as working or studying, having a GAF-function score of 60 or above, having remission of negative and psychotic symptoms, and not living in a supported housing facility or being hospitalized during the last 2 years before the five-year follow-up interview. RESULTS A total of 40 (15.7%) were found to be recovered, and 76 (29.8%) had a job or were studying after 5 years. Of those working, as many as 20 still had psychotic symptoms. Also notable is that out of the 40 recovered, less than half were recovered after 2 years. Recovery after 5 years was predicted by female sex (OR 2.4, 95% CI 1.0-5.8), higher age (OR 0.91, 95% CI 0.83-0.99), pre-morbid social adaptation (OR 0.72, 95% CI 0.56-0.93), growing up with both parents (OR 2.6, 95% CI 1.0-6.8) and low level of negative symptoms (OR 0.51, 95% CI 0.33 to 0.77) at baseline. DISCUSSION Our findings suggest that a stable social life with normal social functioning has a predictive value for good outcome. These measures might be influenced by negative symptoms, but in the multivariate analysis with negative symptoms included they have an independent effect. Also our findings suggest that, after first-episode psychosis, some patients can still experience psychotic symptoms, but have a job and a fairly stable life.

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

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.

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

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.

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

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.

Predictors of poor adherence to medication among patients with first-episode schizophrenia-spectrum disorder.

Aim: This study sought to identify predictors for poor adherence to medication among patients with first‐episode schizophrenia‐spectrum disorder.