Long-acting antipsychotics: patient\u2019s features and prescribing attitudes in Italy. Findings from the cross-sectional phase of an observational, longitudinal, multicenter study.

Scientific background. Long-acting injectable antipsychotics (LAIs) are considered one of the most important tools for ensuring medication adherence in people with chronic psychosis. In recent times many authors promoted an earlier and broader use of LAIs, considering not only their efficacy in preventing non-adherence (and therefore relapses), but also their potential role in simplifying the daily medication routine, ultimately ameliorating patient\u2019s quality of life. On this background, this study aims at describing how this new perspective influenced prescribing pattern in Community Psychiatry Services, with a specific interest in comparing first- and second-generation antipsychotics. Methods. The STAR Network \u201cDepot\u201d Study is an observational, longitudinal, multicenter study involving 35 Italian Community Psychiatry Services. Adult patients initiating a new LAI were recruited over a 12-months period and assessed for relevant socio-demographic and clinical features (employing also validated rating scales) at baseline, after 6 and 12 months. Descriptive statistics and a stepped multivariate logistic model accounting for the inter-center variability were employed. Results. Only results from the recruitment (or cross-sectional) phase will be discussed here. Four-hundred-fifty-one patients, mostly males over their 30s, were recruited. Patients were heterogeneously distributed between higher and lower levels of education, social functioning, overall symptom profiles and medication adherence. Beside schizophrenia, also bipolar disorders, personality disorders and mental organic conditions were well represented. Paliperidone and aripiprazole were the most frequently prescribed medications. Analyses showed that, compared to first-generation LAIs, second-generation LAIs were more likely to be prescribed to younger, employed patients, with higher affective symptoms, a diagnosis different from schizophrenia or bipolar disorder, and fewer previous LAI prescriptions. Discussion. LAIs are prescribed to heterogeneous populations of patients, often even off-label. The advocated paradigm shift is under way in clinical practice, although it appears to be largely limited to second-generation LAIs

Calling for policy actions to increase access to long-acting antipsychotics in low-income and middle-income countries

Schizophrenia-spectrum disorders are associated with substantial impairment and disability. Lack of treatment adherence is a major issue, especially in low- and middle-income countries (LMICs). Despite growing evidence supporting second-generation long-acting antipsychotics (LAIs) as an effective strategy to ensure continued maintenance treatment in schizophrenia, access to these technologies has been very limited in constrained-resource settings. Including second-generation LAIs in national and international essential medicines lists and evidence-based guidelines, promoting public health-oriented patent pooling and extending their availability to primary health care settings, are key actions that should urgently be implemented to increase access to long-acting technologies. Implementing these policy actions can pragmatically improve treatment adherence, ultimately tackling schizophrenia-related impairment and disability in LMICs, which can be regarded as a global health priority

Ground-breaking change to the mental health section of the WHO Model List of Essential Medicines: implications for low- and middle-income countries

[no abstract available

Crossroads of methodological choices in research synthesis: insights from two network meta-analyses on preventing relapse in schizophrenia

In recent years, network meta-analyses have been increasingly carried out to inform clinical guidelines and policy. This approach is under constant development, and a broad consensus on how to carry out several of its methodological and statistical steps is still lacking. Therefore, different working groups might often make different methodological choices based on their clinical and research experience, with possible advantages and shortcomings. In this contribution, we will critically assess two network meta-analyses on the topic of pharmacological prevention of relapse in schizophrenia, carried out by two different research groups. We will highlight the implications of different methodological choices on the analysis results and their clinical-epidemiological interpretation. Moreover, we will discuss some of the most relevant technical issues of network meta-analyses for which there is not a broad methodological agreement, including the assessment of transitivity

Poor implementation of the EU clinical trial regulation is a major threat for pragmatic trials in European countries

The principle of pragmatism in clinical trials has been broadly recognised as a way to close the gap between research and practice. In this contribution, we argue that the conduct of pragmatic clinical trials in Europe may be hampered by poor implementation of current European Union's Clinical Trial Regulation No. 536/2014

Predicted Electronic Shifts in Flourinated Naphthalenes

BACKGROUND: In recent years there has been a progressive rise in the number of asylum seekers and refugees displaced from their country of origin, with significant social, economic, humanitarian and public health implications. In this population, up-to-date information on the rate and characteristics of mental health conditions, and on interventions that can be implemented once mental disorders have been identified, are needed. This umbrella review aims at systematically reviewing existing evidence on the prevalence of common mental disorders and on the efficacy of psychosocial and pharmacological interventions in adult and children asylum seekers and refugees resettled in low, middle and high income countries. METHODS: We conducted an umbrella review of systematic reviews summarizing data on the prevalence of common mental disorders and on the efficacy of psychosocial and pharmacological interventions in asylum seekers and/or refugees. Methodological quality of the included studies was assessed with the AMSTAR checklist. RESULTS: Thirteen reviews reported data on the prevalence of common mental disorders while fourteen reviews reported data on the efficacy of psychological or pharmacological interventions. Although there was substantial variability in prevalence rates, we found that depression and anxiety were at least as frequent as post-traumatic stress disorder, accounting for up to 40% of asylum seekers and refugees. In terms of psychosocial interventions, cognitive behavioral interventions, in particular narrative exposure therapy, were the most studied interventions with positive outcomes against inactive but not active comparators. CONCLUSIONS: Current epidemiological data needs to be expanded with more rigorous studies focusing not only on post-traumatic stress disorder but also on depression, anxiety and other mental health conditions. In addition, new studies are urgently needed to assess the efficacy of psychosocial interventions when compared not only with no treatment but also each other. Despite current limitations, existing epidemiological and experimental data should be used to develop specific evidence-based guidelines, possibly by international independent organizations, such as the World Health Organization or the United Nations High Commission for Refugees. Guidelines should be applicable to different organizations of mental health care, including low and middle income countries as well as high income countries

Early pharmacological interventions for preventing post-traumatic stress disorder (PTSD): a network meta-analysis

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the efficacy and acceptability of pharmacological interventions for preventing post‐traumatic stress disorder (PTSD) in adults exposed to a traumatic event and to generate a clinically useful ranking of pharmacological interventions according to their efficacy and acceptability by performing a network meta‐analysis

Mapping the evidence on pharmacological interventions for non-affective psychosis in humanitarian non-specialised settings: a UNHCR clinical guidance.

BACKGROUND: Populations exposed to humanitarian emergencies are particularly vulnerable to mental health problems, including new onset, relapse and deterioration of psychotic disorders. Inadequate care for this group may lead to human rights abuses and even premature death. The WHO Mental Health Gap Action Programme Intervention Guide (mhGAP-IG), and its adaptation for humanitarian settings (mhGAP-HIG), provides guidance for management of mental health conditions by non-specialised healthcare professionals. However, the pharmacological treatment of people with non-affective psychosis who do not improve with mhGAP first-line antipsychotic treatments is not addressed. In order to fill this gap, UNHCR has formulated specific guidance on the second-line pharmacological treatment of non-affective psychosis in humanitarian, non-specialised settings. METHODS: Following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, a group of international experts performed an extensive search and retrieval of evidence on the basis of four scoping questions. Available data were critically appraised and summarised. Clinical guidance was produced by integrating this evidence base with context-related feasibility issues, preferences, values and resource-use considerations. RESULTS: When first-line treatments recommended by mhGAP (namely haloperidol and chlorpromazine) are not effective, no other first-generation antipsychotics are likely to provide clinically meaningful improvements. Risperidone or olanzapine may represent beneficial second-line options. However, if these second-line medications do not produce clinically significant beneficial effects, there are two possibilities. First, to switch to the alternative (olanzapine to risperidone or vice versa) or, second, to consider clozapine, provided that specialist supervision and regular laboratory monitoring are available in the long term. If clinically relevant depressive, cognitive or negative symptoms occur, the use of a selective serotonin reuptake inhibitor may be considered in addition or as an alternative to standard psychological interventions. CONCLUSIONS: Adapting scientific evidence into practical guidance for non-specialised health workers in humanitarian settings was challenging due to the paucity of relevant evidence as well as the imprecision and inconsistency of results between studies. Pragmatic outcome evaluation studies from low-resource contexts are urgently needed. Nonetheless, the UNHCR clinical guidance is based on best available evidence and can help to address the compelling issue of undertreated, non-affective psychosis in humanitarian settings

Pharmacological treatment of hyperactive delirium in people with COVID-19: rethinking conventional approaches

People with coronavirus disease (COVID-19) might have several risk factors for delirium, which could in turn notably worsen the prognosis. Although pharmacological approaches for delirium are debated, haloperidol and other first-generation antipsychotics are frequently employed, particularly for hyperactive presentations. However, the use of these conventional treatments could be limited in people with COVID-19, due to the underlying medical condition and the risk of drug-drug interactions with anti-COVID treatments. On these premises, we carried out a rapid review in order to identify possible alternative medications for this particular population. By searching PubMed and the Cochrane Library, we selected the most updated systematic reviews of randomised trials on the pharmacological treatment of delirium in both intensive and non-intensive care settings, and on the treatment of agitation related to acute psychosis or dementia. We identified medications performing significantly better than placebo or haloperidol as the reference treatment in each population considered, and assessed the strength of association according to validated criteria. In addition, we collected data on other relevant clinical elements (i.e. common adverse events, drug-drug interactions with COVID-19 medications, daily doses) and regulatory elements (i.e. therapeutic indications, contra-indications, available formulations). A total of 10 systematic reviews were included. Overall, relatively few medications showed benefits over placebo in the four selected populations. As compared with placebo, significant benefits emerged for quetiapine and dexmedetomidine in intensive care unit (ICU) settings, and for none of the medications in non-ICU settings. Considering also data from indirect populations (agitation related to acute psychosis or dementia), aripiprazole, quetiapine and risperidone showed a potential benefit in two or three different populations. Despite limitations related to the rapid review methodology and the use of data from indirect populations, the evidence retrieved can pragmatically support treatment choices of frontline practitioners involved in the COVID-19 outbreak, and indicate future research directions for the treatment of delirium in particularly vulnerable populations

Clinical trajectories of individuals with severe mental illness continuing and discontinuing long-acting antipsychotics: a one-year mirror-image analysis from the STAR Network Depot study

Evidence on long-acting antipsychotics (LAIs) in unselected populations with severe mental illness is scant. In this mirror-image study, we compared multiple clinical outcomes 1 year before and after a first LAI prescription in adults with severe mental illness, describing clinical trajectories of LAI continuers and discontinuers. We compared LAI continuers and discontinuers through Mann–Whitney U test, Kaplan–Meier survival curves, regression for interval-censored data, and a maximum-likelihood mixed-model with individual random-effect and time as predictor. Of the 261 participants analyzed, 71.3% had schizophrenia-spectrum disorders, and 29.5% discontinued the LAI before 1 year. At baseline, LAI discontinuers had a shorter illness duration, lower attitude and adherence scores. The mirror-image analysis showed reduced hospital admissions only for LAI continuers. Over time, continuers spent less days hospitalized, but had more adverse events and more antipsychotics prescribed, with higher overall doses. In conclusion, this study shows that LAIs might be beneficial in unselected patient populations, provided that adherence is maintained. LAI continuers spent less time hospitalized, but received more antipsychotics and suffered from more cumulative adverse events over time. Therefore, the choice of initiating and maintaining a LAI should be carefully weighed on a case-by-case basis