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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods/Design</p> <p>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.</p> <p>Discussion</p> <p>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.</p> <p>Trial Registration</p> <p><b>Clincaltrials.gov Identifier</b>: NCT00395915</p

Are PID-5 personality traits and self-harm attitudes related? A study on a young adult sample pre-post COVID-19 pandemic

Introduction: Different studies confirm a stronger link between maladaptive personality traits and Non-suicidal Self-injury (NSSI). Additionally, the interest in the relationship between the experience of the COVID-19 pandemic and NSSI is growing. The present study aims (a) to investigate differences in personality traits between individuals with NSSI, suicidal ideation, NSSI and suicidal ideation co-occurrence and none; (b) to observe which personality traits predominantly influence the occurrence of self-harm acts; (c) to evaluate the difference in self-harm attitudes pre and post COVID-19 pandemic Method: 270 (108 males and 162 females) participants aged between 18 and 25 were included in the study. Everyone participated in a clinical interview and completed an assessment consisting of the Personality Inventory for DSM-5 (PID-5) and the Health of the Nation Outcome Scales (HoNOS). A multivariate analysis of variance (MANOVA), a multiple hierarchical regression analysis, controlling for age and gender and a T-test for independent samples were conducted. Results: The individuals with the highest levels of negative affectivity, detachment, antagonism, and psychoticism are those who simultaneously present suicidal ideation and NSSI. Moreover, age and detachment predicted higher scores in self-harm attitudes. Our results unexpectedly do not confirm an upward trend of NSSI and suicidal ideation during the pandemic period. Limitations: The study is cross-sectional, and no causal links can be assumed; the groups involved were not homogeneous for numerosity. Conclusions: The results testify that the study of maladaptive traits is fundamental to a greater understanding of NSSIs. Working clinically on those could potentially reduc

Personality traits and transition to psychosis one year after the first assessment

IntroductionSeveral studies have identified ultra-high-risk criteria that may characterize an at-risk mental state and predict the transition of psychotic evolution. Personality traits may play a crucial role in this process.AimsThe current study aims to: (a) explore the evolution of an initial diagnosis over 12 months; (b) assess differences in social and occupational functioning; (c) identify common (trans-diagnostic) personality traits of psychotic risk.MethodsThe sample includes 97 (44 males and 53 females) young adults. They completed an assessment that consists of socio-demographic data, the Social and Occupational Functioning Scale, the Early Recognition Inventory-retrospective assessment onset of schizophrenia, and the Personality Inventory for DSM-5 (PID-5). According to the tests’ assessment, the sample was divided into three different groups: Ultra-High Risk (UHR), At-Risk, and Not at risk. One year after the first evaluation, psychiatrists administered the QuickSCID-5 to verify the diagnostic trajectories of the sample.ResultsOverall, the most prevalent category diagnoses were anxiety/depression, personality disorders, and psychosis. Specifically, the most common diagnosis in the UHR group was psychosis. Moreover, in the UHR group, the social and occupational functioning score was the lowest. In terms of differences in PID-5 personality traits, the At-risk and UHR groups scored highest in detachment and disinhibition. No statistically significant differences were found between the groups for negative affectivity, antagonism, and psychoticism traits.ConclusionResults obtained by the current study should be considered an attempt to better understand the diagnostic trajectories and trans-diagnostic personality traits in a group of young help-seekers, specifically in UHR. Findings highlight both the importance of diagnosis and personality traits evaluation to customize a specific intervention based on the level of psychotic risk. Clinical suggestions are reported

Renaming ultra-high risk (UHR): Italian patients’, caregivers’, and clinicians’ attitudes towards established and newly generated terms to describe psychosis risk status

Introduction: Diagnostic terms in psychiatry can potentially deliver useful information and offer a basic understanding of clinical concepts for young individuals under care in mental health services, carers (i.e., close family members who care for the young patient), and clinicians. However, the use of stigmatizing labels has frequently been associated with poor engagement with clinical services and poor outcomes. Further, using informative and non-stigmatizing terms is crucial in youth with a clinical high-risk for psychosis (CHR-P) status since they both risk being stigmatized and receiving inappropriate treatments (i.e., antipsychotics). Based on pivotal research conducted in Australia, this study aimed to explore the acceptability and preference of both already used and newly generated diagnostic terms, as well as the most appropriate timing and context of diagnosis disclosure in an Italian sample of CHR-P patients, their carers, and clinicians. Methods: In a focus group with individuals with a lived experience of mental disorder, three alternative diagnostic terms were generated: “Tendenza alla psicosi,” “Alterazione della realtà personale,” and “Accenni di disregolazione della soggettività.” Then, a questionnaire was constructed and administered to 31 patients, 45 carers, and 59 clinicians in order to explore attitudes towards both newly generated and well-established terms (i.e., "Ad alto rischio di psicosi – Ultra high risk for psychosis [UHR]," "Sindrome psicotica attenuata," and "Stato mentale a rischio"). T- tests or Chi-square tests were used to analyze descriptive data gathered from the three groups. One- way ANOVA was performed to identify between-group differences, followed by post-hoc Bonferroni test. Results: We found the term "UHR" was considered stigmatizing and did not explain youth difficulties according to both patients and carers (although clinicians reported it was illustrative of the youth's difficulties). On the contrary, "Stato mentale a rischio" was one of the most preferred and illustrative terms for patients and clinicians. Concerning the new terms, "Tendenza alla psicosi" was one of the most preferred by patients and carers – even though clinicians considered it a stigmatizing term. Mixed results were found among groups about the opinions on "Alterazioni della soggettività." All groups agreed that diagnostic terms should be disclosed when the patient has established a trusting relationship with the clinician. Feedback on the diagnosis context varied among groups (nevertheless, more than half of the participants of each group agreed that the presence of the psychiatrist was necessary for the diagnosis disclosing). Conclusion: Findings highlighted the need for "renaming" the term UHR – at least in our Italian sample. Attitudes towards newly generated terms were mixed, with "Tendenza alla psicosi" being one the most appreciated by both youth and carers (but not clinicians). The already used "Stato mentale a rischio" showed to be one of the most preferred and not associated with high stigma – confirming its usefulness in clinical practice. Further research with broader samples is warranted to shed light on mixed results. Nevertheless, in order to promote engagement with early prevention services, the use of less stigmatizing terms and specific attention to the preferences over the diagnosis disclosure context are strongly needed

Personality traits and transition to psychosis one year after the first assessment

Introduction: Several studies have identified ultra-high-risk criteria that may characterize an at-risk mental state and predict the transition of psychotic evolution. Personality traits may play a crucial role in this process. Aims: The current study aims to: (a) explore the evolution of an initial diagnosis over 12 months; (b) assess differences in social and occupational functioning; (c) identify common (trans-diagnostic) personality traits of psychotic risk. Methods: The sample includes 97 (44 males and 53 females) young adults. They completed an assessment that consists of socio-demographic data, the Social and Occupational Functioning Scale, the Early Recognition Inventory-retrospective assessment onset of schizophrenia, and the Personality Inventory for DSM-5 (PID-5). According to the tests’ assessment, the sample was divided into three different groups: Ultra-High Risk (UHR), At-Risk, and Not at risk. One year after the first evaluation, psychiatrists administered the QuickSCID-5 to verify the diagnostic trajectories of the sample. Results: Overall, the most prevalent category diagnoses were anxiety/depression, personality disorders, and psychosis. Specifically, the most common diagnosis in the UHR group was psychosis. Moreover, in the UHR group, the social and occupational functioning score was the lowest. In terms of differences in PID-5 personality traits, the At-risk and UHR groups scored highest in detachment and disinhibition. No statistically significant differences were found between the groups for negative affectivity, antagonism, and psychoticism traits. Conclusion: Results obtained by the current study should be considered an attempt to better understand the diagnostic trajectories and trans-diagnostic personality traits in a group of young help-seekers, specifically in UHR. Findings highlight both the importance of diagnosis and personality traits evaluation to customize a specific intervention based on the level of psychotic risk. Clinical suggestions are reported

At-risk mental states and personality traits: A cluster analysis approach on a group of help-seeking young adults

IntroductionResearch on the relationship between personality and psychosis onset is growing, with the goal of preventing or intervening early in patients' vulnerability. The identification of individuals with at-risk mental states has enabled the development of early intervention strategies, such as Programma 2000, a youth mental health service that was implemented in Milan (Italy). AimsFocusing on the 18-25 age range-the time window with the highest incidence of psychotic onset-this study aims to identify the personality traits that may characterize the at-risk mental states and the social functioning of a group of help-seeking young adults. MethodsThe sample includes 169 people (48.5% males and 51.5% females). Data were collected during an initial assessment that comprised the Social and Occupational Functioning Assessment Scale, the Personality Inventory for DSM-5, the Checklist ERIraos and a clinical session. ResultsResults identified a three-cluster solution based on the Checklist scores: Cluster 1 'Not at psychotic risk'; Cluster 2 'At intermediate risk'; Cluster 3 'With psychotic onset'. The multivariate analysis of the variance of personality traits shows significant differences among the clusters in negative affect, detachment and disinhibition. Higher scores in these traits may distinguish individuals, not at psychotic risk from those at intermediate risk or with psychotic onset. Moreover, social functioning was found to be negatively associated with clusters of psychotic risk. ConclusionFindings from this study highlighted the need to evaluate personalized interventions targeting such personality traits that could prevent psychotic transition and promote psychological well-being

Consequences of the COVID-19 pandemic on admissions to general hospital psychiatric wards in Italy: Reduced psychiatric hospitalizations and increased suicidality

Aims: The present investigation aimed at evaluating differences in psychiatric hospitalizations in Italy during and after the lockdown due to the novel coronavirus disease 2019 (COVID-19), compared to the same periods in 2018 and 2019. Methods: We obtained and analyzed anonymized data on psychiatric admissions (n = 4550) from 12 general hospital psychiatric wards (GHPWs) in different Italian regions (catchment area = 3.71 millions of inhabitants). Using a mixed-effects Poisson regression model, we compared admission characteristics across three periods: (a) March 1-June 30, 2018 and 2019; (b) March 1-April 30, 2020 (i.e., lockdown); and (c) May 1-June 30, 2020 (i.e., post-lockdown). Results: During the COVID-19 lockdown, there was a 41% reduction (IRR = 0.59; p 65 years) was observed in the lockdown (40%; IRR = 0.60; 95% CI: 0.44-0.82) and post-lockdown (28%; IRR = 0.72; 95% CI: 0.54-0.96) periods. Long-stay admissions (>14 days) increased (63%; IRR = 1.63; 95% CI: 1.32-2.02) during the lockdown and decreased by 39% thereafter (IRR = 0.61; 95% CI: 0.49-0.75). A significant 35% increase in patients reporting suicidal ideation was observed in the post-lockdown period, compared to the rate observed in the 2018 and 2019 control period (IRR = 1.35; 95% CI: 1.01-1.79). Conclusion: The COVID-19 lockdown was associated with changes in the number of psychiatric admissions, particularly for older patients and long-stay hospitalizations. Increased admission of patients reporting suicidal ideation in the post-lockdown period merits special attention. Further studies are required to gain insight into the observed phenomena