Marianne Melau

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.

Cognitive and clinical predictors of functional capacity in patients with first episode schizophrenia.

BACKGROUND The predictors of functional capacity in first episode schizophrenia among seven separable cognitive domains and clinical variables are unknown. AIM To investigate predictors of functional capacity in first episode schizophrenia and the associations between functional capacity and measures of real-world functioning. METHODS Socio-demographic, clinical, and cognitive measures from a sample of patients with first episode schizophrenia spectrum disorders aged 18-34years (N=117) were examined at baseline, 4-month follow-up, and 10-month follow-up and used to predict concurrent and longitudinal functional capacity. Symptoms were assessed with the Positive and Negative Syndrome Scale, cognitive functioning with the MATRICS Cognitive Consensus Battery, and functional capacity with the brief version of the University of California San Diego Performance-based Skills Assessment. Linear and logistic regression analyses were adjusted for age, gender, and site. RESULTS Working memory, negative symptoms, and social cognition accounted for 41% of the variance in functional capacity at baseline. Longitudinally, verbal learning, working memory, and negative symptoms predicted 4-month functional capacity. Working memory and visual learning predicted 10-month functional capacity. Functional capacity was associated to global functioning in the univariate analysis, but in multivariable analyses global functioning, financial independence, and independent living were predicted by negative symptoms or general symptoms explaining 15-23% of the variance. CONCLUSIONS The strongest single predictor of functional capacity is working memory, followed by negative symptoms. Clinical symptoms, but not functional capacity, predicted real-world functioning. The usability of the UPSA-B in first episode schizophrenia is discussed. Neurocom, ClinicalTrials.gov Identifier: NCT00472862, http://clinicaltrials.gov/ct2/show/NCT00472862?term=neurocom&rank=1.

Cognitive remediation combined with an early intervention service in first episode psychosis

This randomised clinical trial assessed the effects of a 16‐week cognitive remediation programme (NEUROCOM) combined with an early intervention service (EIS) vs. EIS alone.

Five years of specialised early intervention versus two years of specialised early intervention followed by three years of standard treatment for patients with a first episode psychosis: randomised, superiority, parallel group trial in Denmark (OPUS II)

Objective To compare the effects of five years of specialised early intervention (SEI) treatment for first episode schizophrenia spectrum disorder with the standard two years of SEI plus three years of treatment as usual. Design Randomised, superiority, parallel group trial with blinded outcome assessment. Randomisation was centralised and computerised with concealed randomisation sequence carried out at an external site. Setting Participants were recruited from six OPUS teams in Denmark between 2009 and 2012. OPUS teams provide SEI treatment to all patients diagnosed with a schizophrenia spectrum disorder in Denmark. Participants 400 participants (51% women) with a mean age of 25.6 (standard deviation 4.3) were randomised to five years of SEI (experimental intervention; n=197) or to two years of SEI plus three years of treatment as usual (control; n=203). Interventions OPUS treatment consists of three core elements—modified assertive community treatment, family involvement, and social skill training—with a patient-case manager ratio of no more than 12:1. For participants randomised to five years of OPUS treatment, the treatment was largely unchanged. Participants randomised to the control group were mostly referred to community health centres after two years of SEI treatment. Main outcomes Follow-up assessments were conducted five years after start of OPUS treatment. Primary outcome was negative symptoms measured on the scale for assessment of negative symptoms (avolition-apathy, anhedonia, alogia, and affective blunting). Secondary outcomes were remission of both negative and psychotic symptoms, psychotic symptoms, suicidal ideation, substance abuse, compliance with medical treatment, adherence with treatment, client satisfaction, days in hospital care, and labour market affiliation. Results Levels of negative symptoms did not differ between the intervention group and control group (1.72 v 1.81 points; estimated mean difference −0.10 (95% confidence interval 0.33 to 0.13), P=0.39). Participants receiving five years of OPUS treatment were more likely to remain in contact with specialised mental health services (90.4% v 55.6%, P<0.001), had higher client satisfaction (estimated mean difference 2.57 points (95% confidence interval 1.36 to 3.79), P<0.001), and had a stronger working alliance (estimated mean difference 5.56 points (95% confidence interval 2.30 to 8.82), P=0.001) than the control group. Conclusions This trial tests SEI treatment for up to five years for patients with first episode schizophrenia spectrum disorder; previous trials have found treatment effects for programmes lasting from one to three years. The prolonged SEI treatment had few effects, which could be due to the high level of treatment provided to control participants and the late start of specialised treatment. Trial registration Clinicaltrial.gov NCT00914238.

Cognitive training plus a comprehensive psychosocial programme (OPUS) versus the comprehensive psychosocial programme alone for patients with first-episode schizophrenia (the NEUROCOM trial): a study protocol for a centrally randomised, observer-blinded multi-centre clinical trial.

BackgroundUp to 85% of patients with schizophrenia demonstrate cognitive dysfunction in at least one domain. Cognitive dysfunction plays a major role in functional outcome. It is hypothesized that addition of cognitive training to a comprehensive psychosocial programme (OPUS) enhances both cognitive and everyday functional capacity of patients more than the comprehensive psychosocial programme alone.MethodsThe NEUROCOM trial examines the effect on cognitive functioning and everyday functional capacity of patients with schizophrenia of a 16-week manualised programme of individual cognitive training integrated in a comprehensive psychosocial programme versus the comprehensive psychosocial programme alone. The cognitive training consists of four modules focusing on attention, executive functioning, learning, and memory. Cognitive training involves computer-assisted training tasks as well as practical everyday tasks and calendar training. It takes place twice a week, and every other week the patient and trainer engage in a dialogue on the patients cognitive difficulties, motivational goals, and progress in competence level. Cognitive training relies on errorless learning principles, scaffolding, and verbalisation in its effort to improve cognitive abilities and teach patients how to apply compensation strategies as well as structured problem solving techniques. At 16-week post-training and at ten-months follow-up, assessments are conducted to investigate immediate outcome and possible long-term effects of cognitive training. We conduct blinded assessments of cognition, everyday functional capacity and associations with the labour market, symptom severity, and self-esteem.DiscussionResults from four-month and ten-month follow-ups have the potential of reliably providing documentation of the long-term effect of CT for patients with schizophrenia.Trial RegistrationClinicaltrials.gov NCT00472862.

The effect of duration of untreated psychosis and treatment delay on the outcomes of prolonged early intervention in psychotic disorders

The duration of untreated psychosis (DUP) has been shown to have an effect on outcome after first-episode psychosis. The premise of specialized early intervention (SEI) services is that intervention in the early years of illness can affect long-term outcomes. In this study, we investigate whether DUP affects treatment response after 5 years of SEI treatment compared to 2 years of SEI treatment. As part of a randomized controlled trial testing the effect of prolonged SEI treatment 400 participants diagnosed within the schizophrenia spectrum were recruited. For this specific study participants were dichotomized based on DUP, treatment delay, and time from first symptom until start of SEI treatment. The groups were analyzed with regard to treatment response on psychopathology, level of functioning, and cognitive functioning. The participants with a short DUP had a tendency to respond better to the prolonged treatment with regards to disorganized and negative dimension. For participants with short duration from first symptom until start of SEI treatment there was a significant difference on the negative dimension favoring the prolonged OPUS treatment. The finding of an effect of prolonged treatment for participants with a short total treatment delay could mean that prolonged SEI treatment is more beneficial than treatment as usual (TAU) so long as it is provided in the early years of illness and not just in the early years after diagnosis.Treatment timing: The earlier the betterThe duration of untreated psychosis influences the long-term outcomes of treatment. Nikolai Albert, at the Copenhagen Mental Health Centre, and a team of Danish researchers have investigated the effects of a specialized early intervention program (OPUS) in 400 patients diagnosed with schizophrenia spectrum disorders and compared the effects of OPUS after two and five years. Their findings suggest that five years of specialized early intervention was most beneficial when the total duration from symptom start to treatment was shorter than 6 months. The treatment was particularly effective at improving patients’ disorganized behavior and negative symptoms such as blunted emotions and lack of motivation. These findings support previous studies suggesting that patients are more responsive to treatment in the early years of illness and highlight the importance of avoiding delays within the mental health service provision.

Cuando la asistencia no sigue a la evidencia: el caso de la falta de programas de intervención temprana en psicosis en España

There is now sufficient evidence to support the importance of interventions in the early stages of psychosis. The delay in the detection and treatment of the first-episode psychosis is related to a lower and slower recovery, as well as a higher risk of relapse. Despite this fact, early intervention units or teams are still not regularly implemented in mental health service settings in Spain. In this opinion article, a review is presented of the main arguments for defending the need to implement these programs and strategies in order to achieve this aim. There are a number of programs for early intervention for psychosis currently working in other countries, with a therapeutic program that includes pharmacological and psychosocial interventions, together with public awareness, information dissemination, and family-professional collaboration activities. Published literature on the experience of these programs indicates that early intervention is not only effective in terms of the improvement of health status, but is also economically efficient. The main steps and recommendations needed to implement such early intervention programs in our country are described.

Course of illness in a sample of patients diagnosed with a schizotypal disorder and treated in a specialized early intervention setting. Findings from the 3.5 year follow-up of the OPUS II study

BACKGROUND Previous studies report that 20% to 30% of those initially diagnosed with schizotypal disorder go on to develop a psychotic disorder (predominantly schizophrenia). Schizotypal disorder share some traits of those used to identify patients at ultra-high risk for psychosis. METHOD As part of a randomized clinical trial testing the effect of prolonged specialized early intervention, we recruited 83 participants diagnosed with a schizotypal disorder. Participants were recruited 18 months into their two-year treatment program, and follow-up interviews were conducted three and a half year later. They were randomized to either discontinuation after the standard two year treatment or continuation of the specialized treatment for totally five year. The study investigated whether prolonged treatment could affect the rate of transition to psychosis and other clinical outcomes, and what would predict transition to psychosis. RESULTS Of those 59 who attended the follow-up interview 19 (32%) developed a psychotic disorder at follow-up. There were no differences between the two treatment groups on transition rates or clinical outcomes. We found that lower level of functioning at baseline predicted transition to psychosis. DISCUSSION Comparable to previous ultra-high risk studies, we found that level of functioning was the strongest predictor of transition to psychosis. Prior studies have found effect of specialized early intervention on transition rates, but we were not able to reproduce this finding. This may be attributable to the intervention in our study occurring at a later stage in the illness than prior studies.

Fidelity scales and performance measures to support implementation and quality assurance for first episode psychosis services

The purpose of this paper is to review fidelity and outcome measures which can be used to support broad implementation of first episode psychosis services and ensure quality of existing services. First episode psychosis services use a combination of evidence‐based practices to improve the outcome of a first episode of psychosis and the early stages of schizophrenia. Now that there is an established international evidence base to show that they are effective, efforts are being made to make such services widely available as a routine part of health care.

Development of a fidelity scale for Danish specialized early interventions service

BACKGROUND The efficacy of the Specialized Early Intervention (SEI) treatment in Denmark, the OPUS treatment, has in a randomized clinical trial proved to be very effective compared to treatment as usual, and the dissemination of SEI services is increasing in Denmark. A prerequisite for upholding positive effects along with creating new teams and preserving critical components is to ensure fidelity to the model. Currently there is no Danish fidelity scale for SEI services. AIM To establish a fidelity scale for SEI teams, in a brief and easily manageable form, for the use of evaluating and assessing the critical components in Danish SEI services. METHOD We identified essential evidence-based components of SEI services internationally and interviewed experts from five Danish SEI teams, using an adapted version of the Delphi Consensus method. RESULTS An 18-point fidelity scale was constructed. The scale was divided into two dimensions: one relating to the structure of the SEI team and one relating to the character and content of the SEI treatment. Each component can be rated either 1 or 0 (1 point = fulfilling the requirements for the components; and 0 point = the requirements were not met). The maximum score was a total of 18 points with 5 of the components being mandatory. CONCLUSION The development of the fidelity scale is an important tool for securing the quality of SEI treatment in Denmark.