Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia.

BACKGROUND: One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study. METHODS/DESIGN: The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome. DISCUSSION: The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.

[Heterogeneity of the Departments of Mental Health in the Veneto Region ten years after the National Plan 1994-96 for Mental Health. Which implication for clinical practice? Findings from the PICOS Project]. / Eterogeneità dei DSM veneti a dieci anni dal Progetto Obiettivo "Tutela Salute Mentale 1994-96". Quali implicazioni per la pratica clinica? Indagine sui servizi partecipanti al Progetto PICOS-Veneto.

AIMS: This study aims to present data on structural and human resources of public mental health services located in the Veneto Region, Italy, and to discuss them in the light of implementation of the first National Target Plan for Mental Health ("Progetto Obiettivo 1994-1996") ten years after its launch. METHODS: The study was conducted in the context of the PICOS (Psychosis Incident Cohort Outcome Study) Project, a large first-presentation multisite study on patients with psychotic disorders attending community mental heath services in the Veneto Region. Human and structural resources were surveyed in 26 study sites using a structured interview administered by the PICOS local referents. RESULTS: CMHCs and Day Centres were homogeneously distributed across the Region and their overall rates per resident population met the national standards; a wide variability in the distribution of Day Hospitals was found, with the overall rate per resident population very far from meeting the national standard; the overall rate for Residential Facilities beds was higher than the recommended national standard, showing however an high variability across sites. The overall rate of mental health professionals per resident population was only slightly below the national standard: this was mainly achieved thanks to non-profit organizations which supplement the public system with unspecialised professionals; however, a wide variability in the local rates per resident population was found, with the 50% of the sites showing rates far lower the national standard. Specific lack of trained professionals involved in the provision of psychosocial interventions was found in most sites. CONCLUSIONS: A marked variability in human and structural resources across community mental health services in the Veneto Region was found. Possible reasons for this heterogeneity were analysed and implications for mental health care provision were further discussed.