Aripiprazole, Olanzapine and Haloperidol in the Long-Term Treatment of Schizophrenia: The Rationale and Development of the GiSAS Pragmatic Randomized Controlled Trial, a Consideration and Empirical Study of Factors Associated With Recruitment (the GiSAS Survey) and the Concept of Endpoints Using a Secondary Analysis of Existing Data and a Preliminary Analysis of GiSAS Trial Data

This thesis described the development of a pragmatic, randomized clinical trial evaluating the safety and efficacy of antipsychotic treatment in schizophrenia. In the perspective of highlighting some critical issues of the trial design, the thesis focused on the trial's planning and conduct and on the preliminary analysis of the first followed-up subjects. Having experienced significant problems in patient recruitment a survey on perceived inclusion barriers and antipsychotic preference was performed. Investigators mainly complained about system-related barriers, and believed in the superiority of second-generation antipsychotics. Taking the cue from these results, strategies were adopted in order to reach the planned target of 800 subjects. Remedial actions included study promotion activities, education initiatives and bursaries, and resulted in a significant improvement of the recruitment rate. Nevertheless, we had to reduce the sample to one third of the original size. The second part of the thesis focused on the concept of endpoints using a secondary analysis of existing data and a preliminary analysis of GiSAS trial data. The assumption that differences in discontinuation rates reflect differences in effectiveness was reinforced by the results of a pharmaco-epidemiological study comparing the use of reboxetine and SSRIs in a large population sample. The established lack of efficacy of this antidepressant was mirrored by a higher proportion of treatment discontinuations. We explored the baseline characteristics of 114 included subjects and compared the baseline and follow-up variables between those who discontinued study drugs at follow-up and those who did not. Discontinues' worse outcome was mainly attributable to self reported side-effects. This thesis highlighted some critical issues on the execution of a pragmatic trial in schizophrenia. The feasibility of the trial design and the concept of endpoints were critically analyzed. The trial mechanism is now fully functional and most problems of its implementation have been identified and contained

Use of standardised outcome measures in adult mental health services - Randomised controlled trial

This is an author-produced electronic version of an article accepted for publication in the British Journal of Psychiatry. The definitive publisher-authenticated version is available online at http://bjp.rcpsych.or

The Italian version of the 16-item Prodromal Questionnaire (PQ-16) and its psychometric features in help-seeking ultra-high-risk subjects and in the general population.

BACKGROUND Increasing attention to the early stages of psychosis and the identification of symptomatic prodromal states have led to the development of a growing number of screening tools. The 16-item version of the Prodromal Questionnaire (PQ-16) is a worldwide used self-administered tool for this purpose. However, to date, fundamental psychometric properties of PQ-16 were not thoroughly investigated. This study aimed to examine the structural validity, measurement invariance, reliability and other psychometrical properties of the Italian version of the PQ-16 (iPQ-16) in help-seeking individuals and in the general population. METHODS The iPQ-16 was administered to 449 young outpatients attending six community mental health services and to 318 control participants enrolled in educational environment. Confirmatory factor analyses (CFAs), measurement invariance (MI) between the help-seeking group and the general population sample, convergent validity, test-retest reliability, internal consistency, and prevalence analyses were performed. Lastly, the validity of the adopted PQ-16 cut-offs through Receiver Operating Characteristic (ROC) curves plotted against CAARMS diagnoses was also tested. RESULTS CFAs confirmed the single-factor structure for the iPQ-16 and scalar MI was reached. The iPQ-16 showed high internal consistency, test-retest reliability, convergent validity, and acceptable diagnostic accuracy. ROC analysis suggested a score of ≥4 as best cut-off. CONCLUSIONS The iPQ-16 represents a valid and reliable questionnaire for the assessment of high mental risk in both Italian outpatients and general student population. It has good psychometric properties and is easy to implement as UHR screening for clinical as well as research purposes

Satisfaction with community and hospital-based emergency services amongst severely mentally ill service users

OBJECTIVE: This study compares the satisfaction with emergency interventions among severely mentally ill (SMI) service users of a community-based and a hospital-based mental health service (South-Verona, Italy and Nunhead, South-London, UK). METHODS: A measurement of the satisfaction with psychiatric emergency services was conducted among all those users in the two catchment areas who, in a 1-year period: (1) had at least two contacts with the service; (2) had a diagnosis of psychosis according to ICD10; (3) had not been living in hospital or sheltered apartment for most of the time. These users completed seven items belonging to the Verona Service Satisfaction Scale (VSSS) regarding their satisfaction with crisis response during and out of office hours and their satisfaction with the different interventions, which may be provided during emergencies, such as consultation for the user, consultation for the relative, day-centre attendance, informal and compulsory admission. RESULTS: Users in South-Verona were generally more satisfied with emergency interventions. The main differences between the two samples were due to contacts outside the hospital setting, whilst satisfaction scores for informal admission were similar. The number of users who did not receive, but would have liked, different types of emergency intervention was smaller in South-Verona than in Nunhead. In South-Verona, users wishes mainly concerned consultation for the relatives during emergencies; in the Nunhead sample, the most requested types of intervention were consultation for the user and the possibility of day-centre attendance during crisis. CONCLUSIONS: The findings suggest that users of a service with a well developed community-oriented approach and with crisis intervention outside the hospital setting are more satisfied of the emergency interventions than users of a mental health service relying mostly on hospital facilities during emergencies

Outcome of patients dropping out from community-based mental health care: A 6-year multiwave follow-up study

OBJECTIVE: To test three hypotheses: i) is dropping out of community mental health care due to dissatisfaction? ii) Do those who appropriately interrupt mental health care need any more help? iii) Do those who need treatment continue to receive it? METHOD: A cohort from a Community Mental Health Service in Verona, Italy, was followed up for 6 years, interviewing patients at follow-up who are both in contact and not in contact with the service. RESULTS: The main reason for dropping out was service dissatisfaction. Patients still in contact with the service were more often psychotic. Many patients no longer in contact had mild-to-moderate problems, especially anxiety and depression and some social disability. Patients out of contact rarely sought help from other agencies. CONCLUSION: Comprehensive community mental health services seem to offer good continuity of mental health care to patients with psychosis, but dedicate less attention to patients with less severe problems. Some of these patients will go on experiencing a burden of symptoms and disability, over the years

Association of Antipsychotic Polypharmacy and Two-Year All-Cause Mortality: A Population-Based Cohort Study of 33,221 Italian Continuous Users

Background: Differences in survival between patients treated with antipsychotic monotherapy vs. polytherapy are debated. This study aimed to examine the association of antipsychotic polytherapy with 2-year all-cause mortality in a population-based cohort. Methods: Data were retrieved from healthcare databases of four local health units of Lombardy, Italy. Subjects aged 18–79 years who received continuous antipsychotic prescriptions in 2018 were identified. Overall survival among patients with antipsychotic monotherapy vs. polytherapy was compared. A multivariate Cox PH model was used to estimate the association between antipsychotic therapy, or antipsychotic use (continuous vs. non-continuous), and all-cause mortality. Adjustments were made for the presence of metabolic disturbances, total antipsychotic dosage amount (olanzapine equivalent doses), age, and sex. Results: A total of 49,875 subjects receiving at least one prescription of antipsychotics during 2018 were identified. Among the 33,221 patients receiving continuative antipsychotic prescriptions, 1958 (5.9%) experienced death from any cause at two years. Patients with continuous antipsychotic use had a 1.13-point increased mortality risk compared with non-continuous users. Patients treated with antipsychotic polytherapy showed an adjusted mortality risk increased by 17% (95% CI: 2%, 33%) compared to monotherapy. Conclusions: The study highlights the potential risks associated with antipsychotic polypharmacy, emphasizing the importance of optimizing drug prescriptions to improve patient safety and reduce mortality rates in individuals receiving antipsychotic therapy