Gertrud Krarup

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.

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.

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.

The effect of five years versus two years of specialised assertive intervention for first episode psychosis - OPUS II: study protocol for a randomized controlled trial

BackgroundThe Danish OPUS I trial randomized 547 patients with first-episode psychosis to a two-year early-specialised assertive treatment programme (OPUS) versus standard treatment. The two years OPUS treatment had significant positive effects on psychotic and negative symptoms, secondary substance abuse, treatment adherence, lower dosage of antipsychotic medication, and a higher treatment satisfaction. However, three years after end of the OPUS treatment, the positive clinical effects were not sustained, except that OPUS-treated patients were significantly less likely to be institutionalised compared with standard-treated patients. The major objective of the OPUS II trial is to evaluate the effects of five years of OPUS treatment versus two years of OPUS treatment.MethodsThe OPUS II trial is designed as a randomized, open label, parallel group trial with blinded outcome assessment. Based on our sample size estimation, 400 patients treated in OPUS for two years will be randomized to further three years of OPUS treatment versus standard treatment. The specialized assertive OPUS treatment consists of three core elements: assertive community treatment, psycho-educational family treatment, and social skills training.DiscussionIt has been hypothesized that there is a critical period from onset up to five years, which represents a window of opportunity where a long-term course can be influenced. Extending the specialized assertive OPUS treatment up to five years may allow the beneficial effects to continue beyond the high-risk period, through consolidation of improved social and functional outcome.Trial registrationClinical Trial.gov NCT00914238

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.

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

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.