Anne Thorup

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

Abstract Objectives To evaluate the effects of integrated treatment for patients with a first episode of psychotic illness. Table 2 Clinical outcomes and user satisfaction of patients with a first episode of psychotic illness who received integrated treatment or standard treatment. Values are means (SD) unless stated otherwise 1 year follow-up (n=419) 2 year follow-up (n=369) Integrated treatment (n=227) Standard treatment (n=192) Estimated mean difference (95% CI) P value of difference Integrated treatment (n=205) Standard treatment (n=164) Estimated mean difference (95% CI) P value of difference Psychopathology*: Psychotic dimension 1.09 (1.27) 1.35 (1.39) -0.31 (−0.55 to −0.07) 0.02 1.06 (1.26) 1.27 (1.40) -0.32 (−0.58 to −0.06) 0.02 Negative dimension 1.68 (1.10) 2.02 (1.12) -0.36 (−0.54 to −0.17) <0.001 1.41 (1.15) 1.82 (1.23 -0.45 (−0.67 to −0.22 <0.001 Disorganised dimension 0.40 (0.59) 0.42 (0.56) -0.04 (−0.14 to 0.07) 0.5 0.37 (0.56) 0.50 (0.73) -0.12 (−0.25 to 0.00) 0.06 GAF, symptom 48.2 (14.9) 44.9 (16.0) 3.00 (0.37 to 5.63) 0.03 51.18 (15.01) 48.67 (15.92) 2.45 (−0.32 to 5.22) 0.08 GAF, function 51.7 (15.1) 49.4 (14.6) 2.61 (0.11 to 5.15) 0.04 55.16 (15.15) 51.13 (15.92) 3.12 (0.37 to 5.88) 0.03 User satisfaction† 24.9 (4.5) 23.0 (7.2) 1.88 (0.73 to 3.02) 0.001 26.1 (3.7) 22.9 (5.2) 3.09 (2.10 to 4.04) <0.001 GAF=global assessment of functioning. * Estimated mean differences are based on a repeated measurements model with treatment site, sex, substance misuse, diagnosis at baseline, and baseline values of the scale included as covariates (see text for details). † Based on client satisfaction questionnaire score. Estimated mean differences calculated by analysis of variance with treatment site as covariate. 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 years 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.

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

CONTEXTnIntensive early treatment for first-episode psychosis has been shown to be effective. It is unknown if the positive effects are sustained for 5 years.nnnOBJECTIVEnTo determine the long-term effects of an intensive early-intervention program (OPUS) for first-episode psychotic patients.nnnDESIGNnSingle-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.nnnSETTINGnCopenhagen 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.nnnINTERVENTIONSnTwo 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.nnnMAIN OUTCOME MEASURESnPsychotic and negative symptoms were recorded. Secondary outcome measures were use of services and social functioning.nnnRESULTSnAnalysis 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.nnnCONCLUSIONSnThe 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

PURPOSEnTo investigate the effect of integrated treatment on negative, psychotic and disorganised symptoms in patients with first episode psychosis.nnnMETHODnA 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.nnnRESULTSnIT 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.nnnCONCLUSIONnIntegrated 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

BACKGROUNDnThose with first-episode psychosis are at high-risk of suicide.nnnAIMSnTo 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.nnnMETHODnA 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.nnnRESULTSnSixteen 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.nnnCONCLUSIONSnIn 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

BACKGROUNDnOnly a few randomized clinical trials have tested the effect on transition rates of intervention programs for patients with sub-threshold psychosis-like symptoms.nnnAIMnTo examine whether integrated treatment reduced transition to psychosis for first-contact patients diagnosed with schizotypal disorder.nnnMETHODSnSeventy-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.nnnRESULTSnIn 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.nnnCONCLUSIONnIntegrated treatment postponed or inhibited onset of psychosis in significantly more cases than standard treatment.

Young males have a higher risk of developing schizophrenia: a Danish register study.

BACKGROUNDnGender differences are commonly reported in schizophrenia research, especially with regard to age at onset. Few studies have reported the age- and gender-specific incidence of schizophrenia in people aged up to 71 years, and no studies have reported the cumulative incidence of schizophrenia in people aged up to 71 years.nnnMETHODnTwo cohorts were established by linking data from the Danish Civil Registration System (DCRS) with data from the Danish Psychiatric Central Register (DPCR), which covers all incident cases of schizophrenia from 15 to 71 years. We estimated the gender- and age-specific incidence rates of schizophrenia for people aged up to 71 years. We also estimated the cumulative incidences.nnnRESULTSnThe incidence rates for males significantly exceeded those for females in the age range from 17 to 40 years. By their 72nd birthday, 1.59% of males and 1.17% of females had developed schizophrenia.nnnCONCLUSIONnMale sex is a major risk factor for the development of schizophrenia.

Predictors of remission and recovery in a first-episode schizophrenia spectrum disorder sample: 2-year follow-up of the OPUS trial.

Objective: To examine the frequency and predictors of good outcome for patients with first-episode schizophrenia spectrum disorder (SSD). Method: We conducted a 2-year follow-up of a cohort of patients (n = 547) with first-episode SSD. We evaluated the patients on demographic variables, diagnosis, duration of untreated psychosis (DUP), premorbid functioning, psychotic and negative symptoms, substance abuse, adherence to medication, and service use. ORs were calculated with logistic regression analyses. Results: A total of 369 patients (67%) participated in the follow-up interview. After 2 years, 36% remitted and 17% were considered fully recovered. Full recovery was associated with shorter DUP, better premorbid adjustment, fewer negative symptoms at baseline, no substance abuse at baseline, and adherence to medication and OPUS treatment. Conclusions: Several predictive factors were identified, and focus should be on potentially malleable predictors of outcome, for example, reducing DUP and paying special attention to patients who are unlikely to achieve good outcome, for example, patients with a substance abuse problem and poor premorbid adjustment.

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

BACKGROUNDnInformation about the cost-effectiveness of early intervention programmes for first-episode psychosis is limited.nnnAIMSnTo 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.nnnMETHODnAn incremental cost-effectiveness analysis of a randomised controlled trial, adopting a public sector perspective was undertaken.nnnRESULTSnThe 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%.nnnCONCLUSIONSnThe incremental cost-effectiveness analysis showed that there was a high probability of OPUS being cost-effective compared with standard treatment.

How successful are first episode programs? A review of the evidence for specialized assertive early intervention.

Purpose of review It has been hypothesized that the first 5 years after first episode of psychosis are a critical period with opportunities for ameliorating the course of illness. On the basis of this rationale, specialized assertive early intervention services were developed. We wanted to investigate the evidence basis for such interventions. Recent findings The evidence for the effectiveness of specialized assertive early intervention services is mainly based on one large randomized clinical trial, the OPUS trial, but it is supported by the findings in smaller trials, such as the Lambeth Early Onset trial, the Croydon Outreach and Assertive Support Team trial and the Norwegian site of Optimal Treatment trial. There are positive effects on psychotic and negative symptoms, on substance abuse and user satisfaction, but the clinical effects are not sustainable when patients are transferred to standard treatment. However, the positive effects on service use and ability to live independently seem to be durable. Summary Implementation of specialized assertive early intervention services is recommended, but the evidence basis needs to be strengthened through replication in large high-quality trials. Recommendation regarding the duration of treatment must await results of ongoing trials comparing 2 years of intervention with extended treatment periods.