A Pragmatic Cluster Randomized Controlled Trial of a Multi-element Psychosocial Intervention for Early Psychosis in a 10 Million Inhabitant Catchment Area Aimed to Measure the Treatment's Feasibility and Effectiveness: GET UP-PIANO Trial

BACKGROUND. It has been shown that most clinical and psychosocial deterioration in psychosis occurs within the first 5 years of illness onset, suggesting thereby that this timeframe is a "critical" period for initiating treatment. Research has therefore more recently focused on early detection and intervention for psychosis, showing that the beneficial effects of antipsychotic medication on first-episode psychosis (FEP) are tempered by the fact that, despite initial symptom reduction, functional recovery is typically poor, even when optimal pharmacological treatment is provided. Family members suffer due to the high emotional burden of being caregivers and frequently show signs of psychological distress. Over the last few years, there has been a growing interest in psychosocial intervention as a means of facilitating recovery and reducing long-term disability associated with psychosis. Literature on psychosocial interventions in FEP can be viewed in terms of two broad categories: 1) studies evaluating specific (i.e. single-element) psychosocial interventions (e.g. individual cognitive behavioral therapy), and 2) studies evaluating comprehensive (i.e. multi-element) interventions, which may include early detection strategies, individual, group, and/or family therapy, and case management (in addition to pharmacological treatment). The latter appear very promising and have been found to be associated with symptom reduction/remission, improved quality of life, increased social and cognitive functioning, low inpatient admission rates, improved insight, high degree of satisfaction with treatment, less time spent in hospital, decreased substance abuse, and fewer self- harm episodes. Most multi-element research programs, however, have been conducted on non-epidemiologically representative samples in experimental settings, raising the risk thereby of underestimating the complexities involved in treating FEP in "real world" services. Moreover, these interventions have rarely tested their efficacy against a control group or, if they have done so, they have used historical or prospective comparison groups, or single-group designs, which track the progress of a single group over a given period of time. With respect to practices, over the last 10 years, some countries have implemented specific early psychosis interventions, but even these have not yet become routinely conducted. Few studies have identified barriers that can hinder the feasibility of these interventions or the pinpointing of patient or family conditions that can render this type of ineffective or inappropriate. Hence, efforts to implement these specific multi-element interventions should be accompanied by rigorous scientific methodology, with the aim of better understanding the actual effectiveness of this approach.

AIMS. The PIANO Trial (Psychosis early Intervention and Assessment of Needs and Outcome described herein makes up part of the more broad-based research program Genetics Endophenotypes and Treatment: Understanding early Psychosis (GET UP, National Coordinator: Prof. Mirella Ruggeri, Verona), which is financed by the Italian Ministry of Health as part of a Ricerca Sanitaria Finalizzata and is coordinated by the Azienda Ospedaliera Universitaria Integrata in Verona. GET UP Research Programme consists of 4 partner Projects: PIANO (Psychosis: early Intervention and Assessment of Needs and Outcome); TRUMPET (TRaining and Understanding of service Models for Psychosis Early Treatment); GUITAR (Genetic data Utilization and Implementation of Targeted drug Administration in the clinical Routine); and CONTRABASS (COgnitive Neuroendophenotypes for Treatment and RehAbilitation of psychoses: Brain imaging, inflAmmation and StresS). Each of these partner projects pertains to different areas of research, but are linked together in a high degree of harmonization of effort.

The Trial described herein - which is the main component of GET UP PIANO, and the main data collection axis for the overall GET UP Research Program - aims to: 1) test, at 9 months, the effectiveness, as compared to treatment as usual (TAU) of multi-component psychosocial intervention on a large epidemiologically-based cohort of FEP patients recruited from a 10 million inhabitant catchment area; 2) verify the clinical routine limits of this approach, i.e. to identify barriers that may hinder its feasibility and patient/family conditions that can render this type of treatment ineffective or inappropriate; 3) identify clinical, psychological, and environmental and service predictors of treatment effectiveness in FEP, as undertaken in an Italian community mental health care framework.

Study participants will be recruited from Community Mental Health Centres (CMHCs) operating for the Italian National Health Service and located in several Northern and Central Regions of Italy. Specifically, the Participating Units (PU) will be located in the Veneto Region (subdivided in the Western Veneto and in the Eastern Veneto PU), the Emilia-Romagna Region (subdivided in the Emilia and Romagna PUs) and in the provinces of Florence, Bolzano, and Milano (subdivided in the Milan Niguarda and in the Milan San Paolo PUs), and thus, overall, a 10 million-inhabitant catchment area.

DESIGN. The GET UP PIANO Trial has a pragmatic cluster randomized controlled design, which compares the effectiveness of a multi-element psychosocial treatment for FEP patients and their family members, versus the treatment as usual provided by Italian community mental health services. A cluster design was chosen based on feasibility considerations. In fact, a document drafted by members of the MRC Health Services and Public Health Research Board in 2000 indicated cluster randomisation as the gold standard approach for trials that evaluate complex interventions implemented at the institutional level, with the aim of improving health. The assignment units (clusters) will be the catchment area's CMHC, and the units of observation and analysis will be the Centers' patients and their family members.