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Background: Childhood trauma history has frequently been linked to eating disorders (EDs); nevertheless, the scientific literature calls for extending knowledge regarding mediators between EDs and childhood trauma. This study explored whether ED symptoms and early maladaptive schemas were more severe in ED patients with severe childhood trauma than in ED patients with no/mild childhood trauma and whether early maladaptive schemas mediated the relationship between childhood trauma and ED symptom severity., Methods: Data were extracted from the Regional Centre for Eating Disorders registry at the University Hospital of Verona. The extracted data included self-reported data, including the Eating Disorder Inventory-3 score, Young Schema Questionnaire score, Childhood Experience and Experience of Care and Abuse Questionnaire score, and sociodemographic and clinical information on the ED outpatients seeking care. A mediation analysis using the structural equation modeling procedure was conducted., Results: Forty-two outpatients, 31% of whom exhibited severe childhood trauma, satisfied the criteria for registry data extraction. The severity of ED symptoms, as well as the early maladaptive schemas' scores for emotional deprivation, defectiveness, failure, vulnerability, insufficient self-control, and negativity, were greater in ED outpatients with severe childhood trauma. Furthermore, early maladaptive schemas related to defectiveness, failure, and negativity had a mediating role in the relationship between severe childhood trauma and ED symptom severity., Conclusions: This exploratory study provides preliminary evidence about the importance of early maladaptive schemas in the relationship between trauma history and ED psychopathology. In addition, ED symptoms may represent a dysfunctional attempt to avoid unpleasant emotions associated with schema activation. The results support the need to consider early maladaptive schemas in the treatment of traumatized patients with ED symptoms. Study limitations, research and clinical implications are discussed., (© 2024. The Author(s).)

Background: The COVID-19 pandemic has had an impact on population-wide mental health and well-being. Although people experiencing socioeconomic disadvantage may be especially vulnerable, they experience barriers in accessing mental health care. To overcome these barriers, the World Health Organization (WHO) designed two scalable psychosocial interventions, namely the web-based Doing What Matters in Times of Stress (DWM) and the face-to-face Problem Management Plus (PM+), to help people manage stressful situations. Our study aims to test the effectiveness of a stepped-care program using DWM and PM + among individuals experiencing unstable housing in France - a majority of whom are migrant or have sought asylum., Methods: This is a randomised controlled trial to evaluate the effectiveness and cost effectiveness of a stepped-care program using DWM and PM + among persons with psychological distress and experiencing unstable housing, in comparison to enhanced care as usual (eCAU). Participants (N = 210) will be randomised to two parallel groups: eCAU or eCAU plus the stepped-care program. The main study outcomes are symptoms of depression and anxiety measured using the Patient Health Questionnaire Anxiety and Depression Scale (PHQ-ADS)., Discussion: This randomised controlled trial will contribute to a better understanding of effective community-based scalable strategies that can help address the mental health needs of persons experiencing socioeconomic disadvantage, whose needs are high yet who frequently have limited access to mental health care services., Trial Registration: this randomised trial has been registered at ClinicalTrials.gov under the number NCT05033210., (© 2023. The Author(s).)

Background: The COVID-19 pandemic has negatively affected the mental health of international migrant workers (IMWs). IMWs experience multiple barriers to accessing mental health care. Two scalable interventions developed by the World Health Organization (WHO) were adapted to address some of these barriers: Doing What Matters in times of stress (DWM), a guided self-help web application, and Problem Management Plus (PM +), a brief facilitator-led program to enhance coping skills. This study examines whether DWM and PM + remotely delivered as a stepped-care programme (DWM/PM +) is effective and cost-effective in reducing psychological distress, among Polish migrant workers with psychological distress living in the Netherlands., Methods: The stepped-care DWM/PM + intervention will be tested in a two-arm, parallel-group, randomized controlled trial (RCT) among adult Polish migrant workers with self-reported psychological distress (Kessler Psychological Distress Scale; K10 > 15.9). Participants (n = 212) will be randomized into either the intervention group that receives DWM/PM + with psychological first aid (PFA) and care-as-usual (enhanced care-as-usual or eCAU), or into the control group that receives PFA and eCAU-only (1:1 allocation ratio). Baseline, 1-week post-DWM (week 7), 1-week post-PM + (week 13), and follow-up (week 21) self-reported assessments will be conducted. The primary outcome is psychological distress, assessed with the Patient Health Questionnaire Anxiety and Depression Scale (PHQ-ADS). Secondary outcomes are self-reported symptoms of depression, anxiety, posttraumatic stress disorder (PTSD), resilience, quality of life, and cost-effectiveness. In a process evaluation, stakeholders' views on barriers and facilitators to the implementation of DWM/PM + will be evaluated., Discussion: To our knowledge, this is one of the first RCTs that combines two scalable, psychosocial WHO interventions into a stepped-care programme for migrant populations. If proven to be effective, this may bridge the mental health treatment gap IMWs experience., Trial Registration: Dutch trial register NL9630, 20/07/2021, https://www.onderzoekmetmensen.nl/en/trial/27052., (© 2023. The Author(s).)

Background: The COVID-19 pandemic has had major and potentially long-lasting effects on mental health and wellbeing across populations worldwide. However, these impacts were not felt equally, leading to an exacerbation of health inequalities, especially affecting vulnerable populations such as migrants, refugees and asylum seekers. Aiming to inform the adaptation and implementation of psychological intervention programmes, the present study investigated priority mental health needs in this population group., Methods: Participants were adult asylum seekers, refugees and migrants (ARMs) and stakeholders with experience in the field of migration living in Verona, Italy, and fluent in Italian and English. A two-stage process was carried out to examine their needs using qualitative methods including free listing interviews and focus group discussions, according to Module One of the DIME (Design, Implementation, Monitoring, and Evaluation) manual. Data were analyzed using an inductive thematic analyses approach., Results: A total of 19 participants (12 stakeholders, 7 ARMs) completed the free listing interviews and 20 participants (12 stakeholders and 8 ARMs) attended focus group discussions. Salient problems and functions that emerged during free listing interviews were discussed during the focus group discussions. During the COVID-19 pandemic, ARMs struggled with many everyday living difficulties in their resettlement country due to social and economic issues, revealing a strong influence of contextual factors in determining mental health. Both ARMs and stakeholders highlighted a mismatch between needs, expectations and interventions as factors that may hamper proper implementation of health and social programmes., Conclusions: The present findings could help in the adaptation and implementation of psychological interventions targeting the needs of asylum seekers, refugees and migrants aiming to find a match between needs, expectations, and the corresponding interventions., Trial Registration: Registration number 2021-UNVRCLE-0106707, February 11 2021., (© 2023. The Author(s).)

Introduction: The COVID-19 pandemic has posed a serious health risk, especially in vulnerable populations. Even before the pandemic, people with mental disorders had worse physical health outcomes compared to the general population. This umbrella review investigated whether having a pre-pandemic mental disorder was associated with worse physical health outcomes due to the COVID-19 pandemic., Methods: Following a pre-registered protocol available on the Open Science Framework platform, we searched Ovid MEDLINE All, Embase (Ovid), PsycINFO (Ovid), CINAHL, and Web of Science up to the 6th of October 2021 for systematic reviews on the impact of COVID-19 on people with pre-existing mental disorders. The following outcomes were considered: risk of contracting the SARS-CoV-2 infection, risk of severe illness, COVID-19 related mortality risk, risk of long-term physical symptoms after COVID-19. For meta-analyses, we considered adjusted odds ratio (OR) as effect size measure. Screening, data extraction and quality assessment with the AMSTAR 2 tool have been done in parallel and duplicate., Results: We included five meta-analyses and four narrative reviews. The meta-analyses reported that people with any mental disorder had an increased risk of SARS-CoV-2 infection (OR: 1.71, 95% CI 1.09-2.69), severe illness course (OR from 1.32 to 1.77, 95%CI between 1.19-1.46 and 1.29-2.42, respectively) and COVID-19 related mortality (OR from 1.38 to 1.52, 95%CI between 1.15-1.65 and 1.20-1.93, respectively) as compared to the general population. People with anxiety disorders had an increased risk of SAR-CoV-2 infection, but not increased mortality. People with mood and schizophrenia spectrum disorders had an increased COVID-19 related mortality but without evidence of increased risk of severe COVID-19 illness. Narrative reviews were consistent with findings from the meta-analyses., Discussion and Conclusions: As compared to the general population, there is strong evidence showing that people with pre-existing mental disorders suffered from worse physical health outcomes due to the COVID-19 pandemic and may therefore be considered a risk group similar to people with underlying physical conditions. Factors likely involved include living accommodations with barriers to social distancing, cardiovascular comorbidities, psychotropic medications and difficulties in accessing high-intensity medical care., (© 2023. The Author(s).)

Background: To compare the medicines for mental disorders included in national essential medicines lists with the World Health Organization (WHO) essential medicines list and assess the extent to which economic status and WHO Region account for the differences., Methods: We searched WHO repository and government sites for national essential medicines lists and we abstracted medicines for mental disorders. We calculated the proportion of WHO essential medicines included, the total number of differences (counting both additions and deletions) between national and WHO model list and the proportion of lists including one second-generation oral antipsychotic plus one new-generation antidepressant. Non-parametric statistics was used to investigate whether these indicators were dependent on economic status and WHO Region., Results: Amongst the 121 identified national lists, the total number of medicines for mental disorders ranged from 2 to 63 (median: 18; IQR: 14 to 25). The median proportion of WHO essential medicines for mental disorders included was 86% (IQR: 71-93%), with 16 countries (13%, 95% CI 7.75-20.5%) including all WHO essential medicines, while the median number of differences with the WHO EML was 11 (IQR: 7 to 15). Country economic level was positively associated with both the proportion of WHO essential medicines included (Spearman's rho = 0.417, p < 0.001) and the number of differences (Spearman's rho = 0.345, p < 0.001), implying that countries with higher income level included more WHO essential medicines, but also more additional medicines. Significant differences were observed in relation to WHO Region, with the African and Western Pacific Region showing the lowest proportions of WHO essential medicines, and the European Region showing the highest median number of differences. Overall, 88 national lists (73%, 95% CI 63-80%) included at least one second-generation oral antipsychotic and new-generation antidepressant, with differences by income level and WHO Region., Conclusions: The degree of alignment of national lists with the WHO model list is substantial, but there are considerable differences in relation to economic status and WHO Region. These findings may help decision-makers to identify opportunities to improve national lists, aiming to increase access to essential medicines for mental disorders., (© 2023. The Author(s).)

Backgrounds: Individuals with chronic medical conditions are considered highly exposed to COVID-19 pandemic stress, but emerging evidence is demonstrating that resilience is common even among them. We aimed at identifying sustained resilient outcomes and their predictors in chronically ill people during the first year of the pandemic., Methods: This international 4-wave 1-year longitudinal online survey included items on socio-demographic characteristics, economic and living situation, lifestyle and habits, pandemic-related issues, and history of mental disorders. Adherence to and approval of imposed restrictions, trust in governments and in scientific community during the pandemic were also investigated. The following tools were administered: the Patient Health Questionnaire, the Generalized Anxiety Disorder scale, the PTSD Checklist DSM-5, the Oslo Social Support Scale, the Padua Inventory, and the Portrait Values Questionnaire., Results: One thousand fifty-two individuals reporting a chronic condition out of 8011 total participants from 13 countries were included in the study, and 965 had data available for the final model. The estimated probability of being "sustained-resilient" was 34%. Older male individuals, participants employed before and during the pandemic or with perceived social support were more likely to belong to the sustained-resilience group. Loneliness, a previous mental disorder, high hedonism, fear of COVID-19 contamination, concern for the health of loved ones, and non-approving pandemic restrictions were predictors of not-resilient outcomes in our sample., Conclusions: We found similarities and differences from established predictors of resilience and identified some new ones specific to pandemics. Further investigation is warranted and could inform the design of resilience-building interventions in people with chronic diseases., (© 2022. The Author(s).)

Introduction: Information on the off-label use of Long-Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on- vs off-label LAIs and predictors of off-label First- or Second-Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice., Method: In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off- or on-label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off-label group., Results: SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on- and off-label use. Approximately 1 in 4 patients received an off-label prescription. In the off-label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale., Conclusion: Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off-label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co-morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns., (© 2022. The Author(s).)

Background: Low- and middle-income countries (LMICs) host the majority of the world's refugees. Evidence suggests that refugees and asylum seekers have high mental health needs compared to the host country population. However, they face many social, economic and culture barriers to receiving mental health care and benefitting from mental health interventions. This paper examines how these contextual factors affect the implementation of mental health interventions for refugees and asylum seekers in LMICs., Methods: We conducted a qualitative systematic review searching 11 databases and 24 relevant government and non-governmental organisation (NGO) websites. We spoke with academic experts and NGO professionals for recommendations, and conducted forwards and backwards citation tracking., Results: From 2055 records in abstract and title screening, and then 99 in full-text screening, 18 eligible studies were identified. Qualitative thematic synthesis was conducted on eligible papers. Three main thematic clusters were identified around: (1) support during a time of pressure and insecurity, and the need for intervention flexibility through facilitator and participant autonomy; (2) different cultural conceptions of mental health, and how interventions negotiated these differences; and (3) the importance of facilitator skills, knowledge, characteristics and relationships to intervention implementation., Conclusion: Evidence suggests that intervention coordinators and developers should continue to: (1) think broadly about the range of social influences on mental health, addressing structural issues where possible; (2) offer flexibility with intervention style, content and timings; and (3) encourage building research capacity in LMICs while acknowledging pre-existing mental health knowledge and practice., (© 2021. The Author(s).)

Background: People with severe mental disorders (SMD) experience premature mortality mostly from preventable physical causes. The World Health Organization (WHO) have recently produced guidelines on the prevention and management of physical health conditions in SMD. This paper presents the evidence which led to the recommendations presented in the guidelines., Methods: The work followed the methodological principles for WHO guideline development. Systematic reviews in relation to the treatment of seven key priority physical health conditions and associated risk factors in persons with SMD were systematically sourced. The quality of this evidence was assessed, and compiled into evidence profiles. Existing guidelines and treatment recommendations were also considered. Based on this information, specific recommendations were developed on the prevention and management of physical health conditions and their risk factors amongst people with SMD., Results: Nineteen recommendations were made in relation to the seven key priority physical health conditions and risk factors, alongside best practice statements for each condition. A mixture of conditional and strong recommendations were made, the quality of evidence underpinning these was generally low or very low. This is owing to the dearth of direct evidence relating to people living with SMD and comorbidities., Conclusions: This paper presents evidence-based recommendations to prevent and manage physical health conditions in people with SMD. The recommendations are designed to inform policy makers, healthcare providers as well as other stakeholders about what they can do to improve the management of physical health conditions in adults with SMD and support the promotion of individual health behaviors to reduce the risk factors for these conditions. If implemented, these recommendations can improve the care that people with SMD receive for their physical health conditions in an equitable and person-centered manner, so that in future in relation to premature mortality 'no-one is left behind'.

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, public health and mental health implications. The aim of this study is to (1) describe the level of psychological distress and frequency of psychiatric disorders in a sample of male asylum seekers and refugees across different ethnic groups resettled in Italy; (2) establish whether the number of traumatic events experienced before, during and after the migration process is associated with level of psychological distress and depressive symptoms., Methods: In two large Italian catchment areas, over a period of 1 year a consecutive series of male asylum seekers and refugees, aged 18 or above and included in the Italian protection system, were screened for psychological distress and psychiatric disorders using validated questionnaires., Results: During the study period, 252 male asylum seekers or refugees were recruited. More than one-third of the participants (34.5%) showed clinically relevant psychological distress, and one-fourth (22.2%), met the criteria for a psychiatric diagnosis, mainly Post Traumatic Stress Disorder and depressive disorders. The number of traumatic events turned out to be a risk factor for both clinically relevant psychological distress and depressive disorders. Receiving good social support emerged as a protective factor, while migrants with unclear status were at higher risk of psychological distress than those holding or awaiting a permission., Discussion: In an unselected sample of male asylum seekers and refugees, after around 1 year of resettlement in Italy, the frequency of psychological distress and psychiatric disorders was substantial and clinically relevant. The association between traumatic events, especially post-migration problems, and mental health conditions suggests the need of developing services to assist refugees and asylum seekers to address the multi-faceted problems they experience, such as social support in host country, legal problems concerning permit status and asylum procedure, and family reunification, as well as addressing trauma and mental health issues.

An amendment to this paper has been published and can be accessed via the original article.

Introduction: Depression is a highly prevalent condition in the elderly, with a vast impact on quality of life, life expectancy, and medical outcomes. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed agents in this condition and, although generally safe, tolerability issues cannot be overlooked. Vortioxetine is an antidepressant with a novel mechanism of action. Based on studies to date, it may have a promising tolerability profile in the elderly, as it does not adversely affect psychomotor or cognitive performance and does not alter cardiovascular and endocrine parameters. The present study aims to assess the tolerability profile of vortioxetine in comparison with the SSRIs considered as a single group in elderly participants with depression. The rate of participants withdrawing from treatment due to adverse events after 6 months of follow up will be the primary outcome., Methods and Analysis: This is a pragmatic, multicentre, open-label, parallel-group, superiority, randomized trial funded by the Italian Medicines Agency (AIFA - Agenzia Italiana del Farmaco). Thirteen Italian Community Psychiatric Services will consecutively enrol elderly participants suffering from an episode of major depression over a period of 12 months. Participants will be assessed at baseline and after 1, 3 and 6 months of follow up. At each time point, the following validated rating scales will be administered: Montgomery-Åsberg Depression Rating Scale (MADRS), Antidepressant Side-Effect Checklist (ASEC), EuroQual 5 Dimensions (EQ-5D), Short Blessed Test (SBT), and Charlson Age-Comorbidity Index (CACI). Outcome assessors and the statistician will be masked to treatment allocation. A total of 358 participants (179 in each group) will be enrolled., Ethics and Dissemination: This study will fully adhere to the ICH E6 Guideline for Good Clinical Practice. Participants' data will be managed and safeguarded according to the European Data Protection Regulation 2016/679. An external Ethical Advisory Board will help guarantee high ethical standards., Trial Registration: Clinicaltrials.gov: NCT03779789 , Registered on 19 December 2018. Submitted on 19 December. EudraCT number: 2018-001444-66., Trial Status: Protocol version 1.5; 09/06/2018. Recruitment started In February 2019 and it is ongoing. It is expected to end approximately on 30 September 2021.

Background: The novel coronavirus pandemic calls for a rapid adaptation of conventional medical practices to meet the evolving needs of such vulnerable patients. People with coronavirus disease (COVID-19) may frequently require treatment with psychotropic medications, but are at the same time at higher risk for safety issues because of the complex underlying medical condition and the potential interaction with medical treatments., Methods: In order to produce evidence-based practical recommendations on the optimal management of psychotropic medications in people with COVID-19, an international, multi-disciplinary working group was established. The methodology of the WHO Rapid Advice Guidelines in the context of a public health emergency and the principles of the AGREE statement were followed. Available evidence informing on the risk of respiratory, cardiovascular, infective, hemostatic, and consciousness alterations related to the use of psychotropic medications, and drug-drug interactions between psychotropic and medical treatments used in people with COVID-19, was reviewed and discussed by the working group., Results: All classes of psychotropic medications showed potentially relevant safety risks for people with COVID-19. A set of practical recommendations was drawn in order to inform frontline clinicians on the assessment of the anticipated risk of psychotropic-related unfavorable events, and the possible actions to take in order to effectively manage this risk, such as when it is appropriate to avoid, withdraw, switch, or adjust the dose of the medication., Conclusions: The present evidence-based recommendations will improve the quality of psychiatric care in people with COVID-19, allowing an appropriate management of the medical condition without worsening the psychiatric condition and vice versa.

Background: People with severe mental disorders (SMD) experience premature mortality mostly from preventable physical causes. The World Health Organization (WHO) have recently produced guidelines on the management of physical health conditions in SMD. This paper presents the evidence which led to the recommendations for tobacco cessation and management of substance use disorders in SMD., Methods: Scoping reviews informed 2 PICO (Population Intervention, Comparator, Outcome) questions relating to tobacco cessation and management of substance use disorders in SMD. Systematic searches led to the identification of systematic reviews with relevant evidence to address these questions. Retrieved evidence was assessed using GRADE methodology, informing the development of guidelines., Results: One thousand four hundred thirty-four records were identified through systematic searches for SMD and tobacco cessation, of which 4 reviews were included in GRADE tables and 18 reviews in narrative synthesis. For SMD and substance use disorders, 4268 records were identified, of which 4 studies from reviews were included in GRADE tables and 16 studies in narrative synthesis. People with SMD who use tobacco should be offered combined pharmacological (Varenicline, Bupropion or Nicotine Replacement Therapy) and non-pharmacological interventions such as tailored directive and supportive behavioural interventions. For people with SMD and substance use disorders (drug and/or alcohol), interventions should be considered in accordance with WHO mhGAP guidelines. Prescribers should note potential drug-drug interactions. Recommendation were conditional and based on low/very low certainty of evidence with a scarcity of evidence from low- and middle-income settings., Conclusions: These guidelines mark an important step towards addressing premature mortality in people with SMD. The dearth of high-quality evidence and evidence from LMIC settings must inform the future research agenda., Guidelines: https://www.who.int/mental&#95;health/evidence/guidelines&#95;physical&#95;health&#95;and&#95;severe&#95;mental&#95;disorders/en https://www.who.int/publications-detail/mhgap-intervention-guide%2D%2D-version-2.0.

Background: Autism Spectrum Disorder (ASD) is a neuro-developmental disorder that affects communication and behavior with a prevalence of approximately 1% worldwide. Health outcomes of interventions for ASD are largely Participant Reported Outcomes (PROs). Specific guidelines can help support the best care for people with ASD to optimize these health outcomes but they have to adhere to standards for their development to be trustworthy., Objective: The goal of this article is to describe the new methodological standards of the Italian National Institute of Health and novel aspects of this guideline development process. This article will serve as a reference standard for future guideline development in the Italian setting., Methods: We applied the new standards of the Italian National Institute of Health to the two guidelines on diagnosis and management of children/adolescents and adults with ASD, with a focus on the scoping, panel composition, management of conflict of interest, generation and prioritization of research questions, early stakeholders' involvement, and PROs. Recommendations are based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence-to-Decision frameworks., Results: Following a public application process, the ISS established two multidisciplinary panels including people with ASD and/or their caregivers. Seventy-nine research questions were identified as potentially relevant for the guideline on children and adolescents with ASD and 31 for the one on adults with ASD. Questions deemed to have the highest priority were selected for inclusion in the guidelines. Other stakeholders valued their early involvement in the process which will largely focus on PROs. The panels then successfully piloted the development of recommendations using the methodological standards and process set by the ISS with a focus on PROs., Conclusions: In this article, we describe the development of practice guidelines that focus on PROs for the diagnosis and management of ASD based on novel methods for question prioritization and stakeholder involvement. The recommendations allow for the adoption or adaptation to international settings.

Background: Cognitive behavioural therapy has been used for schizophrenia, but to which extent it is effective is still controversial. Results of existing meta-analyses are of difficult interpretation, because they mainly present effect sizes in the form of standardized mean differences between intervention and control groups based on rating scales, which are of unclear clinical meaning. No meta-analysis has considered the number of patients responding to treatment yet. Based on this ground, we present the first meta-analysis examining the response rates of patients with schizophrenia and positive symptoms to cognitive behavioural therapy., Methods: We searched multiple databases for randomized controlled trials on psychological interventions of schizophrenia including patients with positive symptoms, and included for this analysis the studies on cognitive behavioural therapy (last search: January 2018). We applied a validated imputation method to calculate the number of responders from rating scales for the outcomes overall symptoms and positive symptoms, based on two criteria, at least 20% and at least 50% reduction from baseline on PANSS or BPRS total scores. Data were pooled in a single-group summary meta-analysis using R software. Additionally, several potential moderators of response to cognitive behavioural therapy were examined by subgroup and meta-regression analyses. The protocol has been registered in PROSPERO (CRD42017067795)., Results: We included 33 studies with a total of 1142 participants receiving cognitive behavioural therapy. On average, 44.5 and 13.2% of the patients reached a 20% (minimally improved) and 50% (much improved) reduction of overall symptoms. Similarly, 52.9 and 24.8% of the patients reached a 20%/50% reduction of positive symptoms. Subgroup and meta-regression analyses revealed a better treatment response in overall symptoms for patients that were not treatment resistant and in studies with researchers' allegiance. Of borderline significance was the better response in studies employing expert therapists and in patients that were more severely ill at baseline. Blinding of outcome assessor, number of sessions, treatment duration, age and gender were not significant moderators of response., Conclusions: Our findings suggest that adding cognitive behavioural therapy to pharmacotherapy brings about a minimal improvement in overall symptoms among 44.5% of its recipients. Several study and patients characteristics can moderate response rates.

In 1978 Italy implemented Law Number 180, the reform law that blocked all new admissions to public mental hospitals. After 40 years without mental hospitals, we aim at understanding the consequences of the Italian reform in terms of mental health care facility and staff availability. We compared the organization of the Italian mental health system with that of countries belonging to the Group of 7 (G7) major advanced economies. Italy has nearly 8 psychiatrists, 20 nurses, 2 social workers and less than 3 psychologists per 100,000 population, while for example in France there were 22 psychiatrists, in Japan 102 nurses, in the United States 18 social workers, and in Canada and France more than 45 psychologists per 100,000 population. In terms of inpatient facilities, no beds in mental hospitals were available in Italy, while in the other G7 countries mental hospital beds ranged from 8 in the United Kingdom to 204 in Japan per 100 000 population. In Italy there were fewer beds for acute care in general hospitals but more beds in community residential facilities than in the other G7 countries. Service use data showed variability in the provision of mental health care throughout the country. Soon after the implementation of the Italian reform the absolute number of compulsory admissions progressively declined, from more than 20,000 in 1978 to less than 9000 in 2015. Alongside the progressive decline of psychiatric beds imposed by Law 180, the age-adjusted suicide rate remained stable, ranging from 7·1/100,000 population in 1978 to 6·3/100,000 population in 2012. The population of psychiatric patients placed in Italian forensic psychiatric hospitals progressively declined. During the last 40 years without mental hospitals, Italy has seen a progressive consolidation of a community-based system of mental health care. We highlighted, however, reasons for concern, including a decreasing staffing level, a potential use of community residential facilities as long-stay residential services, a still too high variability in service provision across the country, and lack of national data on physical restraints. At a national level, the resources allocated to mental health care are lower in Italy than in other high-income countries.

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.

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.

Background: Only three observational studies investigated whether exposure to antipsychotics is associated with an increased risk of pulmonary embolism, with conflicting results. This study was therefore carried out to establish the risk of pulmonary embolism associated with antipsychotic drugs, and to ascertain the risk associated with first- and second-generation antipsychotic drugs, and with exposure to individual drugs., Methods: We identified 84,253 adult individuals who began antipsychotic treatment in a large Italian health care system. Cases were all cohort members who were hospitalized for non-fatal or fatal pulmonary embolism during follow-up. Up to 20 controls for each case were extracted from the study cohort using incidence density sampling and matched by age at cohort entry and gender. Each individual was classified as current, recent or past antipsychotic user. The occurrence non-fatal or fatal pulmonary embolism was the outcome of interest., Results: Compared to past use, current antipsychotic use more than double the risk of pulmonary embolism (odds ratio 2.31, 95% confidence interval 1.16 to 4.59), while recent use did not increase the risk. Both conventional and atypical antipsychotic exposure was associated with an increase in risk, and the concomitant use of both classes increased the risk of four times (odds ratio 4.21, 95% confidence interval 1.53 to 11.59)., Conclusions: Adding the results of this case-control study to a recent meta-analysis of three observational studies substantially changed the overall estimate, which now indicates that antipsychotic exposure significantly increases the risk of pulmonary embolism.

Background: As lithium treatment might be effective in reducing the risk of deliberate self-harm (DSH) in adult patients with unipolar affective disorders, we designed a pragmatic randomised trial to assess its efficacy in more than 200 patients with treatment-resistant depression. However, we randomised 56 patients only. The aim of this report is therefore twofold: first, to disseminate the results of this underpowered study which may be incorporated into future meta-analytical reviews; second, to analyse some critical aspects of the study which might explain failure to reach the target sample size., Methods: We carried out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode were allocated to add lithium to usual care (intervention arm) versus usual care alone (control arm). Suicide completion and acts of DSH during the 12 months of follow-up constituted the composite primary outcome., Results: Of 58 patients screened for inclusion, 29 were allocated to lithium plus usual care and 27 were assigned to usual care without lithium. Six patients in the lithium plus usual care group and seven in the usual care group committed acts of DSH during the follow-up phase. The survival probability did not differ between the two treatment arms (Chi2 = 0.17, p =0.676). With regard to changes in the severity of depressive symptomatology from baseline to endpoint, no significant differences were detected., Conclusions: The present study failed to achieve the minimum sample size needed to detect a clinically meaningful difference between the two treatment arms. Consequently, the finding that lithium, in addition to usual care, did not exert a positive effect in terms of reduction of DSH after 12 months of follow-up is likely due to the lack of sufficient statistical power to detect a difference, if a difference existed. The dissemination of the results of this underpowered study will inform future meta-analytical reviews on lithium and suicide-related outcomes., Trial Registration: ClinicalTrials.gov identifier: NCT00927550.

Background: Generic atypical antipsychotic drugs offer health authorities opportunities for considerable savings. However, schizophrenia and bipolar disorders are complex diseases that require tailored treatments. Consequently, generally there have been limited demand-side measures by health authorities to encourage the preferential prescribing of generics. This is unlike the situation with hypertension, hypercholaesterolaemia or acid-related stomach disorders.The objectives of this study were to compare the effect of the limited demand-side measures in Western European countries and regions on the subsequent prescribing of risperidone following generics; to utilise the findings to provide future guidance to health authorities; and where possible, to investigate the utilisation of generic versus originator risperidone and the prices for generic risperidone., Methods: Principally, this was a segmented regression analysis of retrospective time-series data of the effect of the various initiatives in Belgium, Ireland, Scotland and Sweden following the introduction of generic risperidone. The study included patients prescribed at least one atypical antipsychotic drug up to 20 months before and up to 20 months after generic risperidone. In addition, retrospective observational studies were carried out in Austria and Spain (Catalonia) from 2005 to 2011 as well as one English primary care organisation (Bury Primary Care Trust (PCT))., Results: There was a consistent steady reduction in risperidone as a percentage of total selected atypical antipsychotic utilisation following generics. A similar pattern was seen in Austria and Spain, with stable utilisation in one English PCT. However, there was considerable variation in the utilisation of generic risperidone, ranging from 98% of total risperidone in Scotland to only 14% in Ireland. Similarly, the price of generic risperidone varied considerably. In Scotland, generic risperidone was only 16% of pre-patent loss prices versus 72% in Ireland., Conclusion: Consistent findings of no increased prescribing of risperidone post generics with limited specific demand-side measures suggests no 'spillover' effect from one class to another encouraging the preferential prescribing of generic atypical antipsychotic drugs. This is exacerbated by the complexity of the disease area and differences in the side-effects between treatments. There appeared to be no clinical issues with generic risperidone, and prices inversely reflected measures to enhance their utilisation.

Background: The burden of mental health and psychosocial problems in children exposed to traumatic events in humanitarian settings in low- and middle-income countries is substantial. An increasing number of randomized studies has shown promising effects of psychosocial interventions, but this evidence has shown complexity with regard to setting, conflict-phase, gender, and age. These complex findings raise the need of a detailed evaluation of the specific factors which influence size and direction of intervention effects.Individual patient data meta-analysis is a specific type of meta-analysis that allows the collection of exact information at an individual patient level, and to examine whether intervention and socio-demographic characteristics, trauma-related variables, environmental conditions, and social support may act as moderators and mediators of intervention effect.The aim of the present study is to carry out an individual patient data meta-analysis using data from all available randomized controlled trials (either published or unpublished) comparing psychosocial intervention with waiting list or no intervention arms in children exposed to traumatic events living in low- and middle-income countries., Methods/design: All randomized trials comparing selective preventive psychosocial intervention versus waiting list or no treatment conditions in children (0-18 years) living in low- and middle-income countries will be included. Studies will be identified in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. There will be no restrictions on publication type, status, language, or date of publication. The primary outcome measures will be psychological symptoms (post-traumatic stress disorder, anxiety, depression). Secondary outcomes will be positive mental health outcomes (coping methods, social support, self-esteem), and function impairment., Discussion: We are expecting that some variables, like socio-demographic characteristics, trauma-related variables, environmental conditions, and social support will act as moderators/mediators of intervention effect. The investigation of the role of these factors on the intervention effects will help in the appropriate selection, development, implementation, and dissemination of evidence-based programs in low- and middle-income countries., Trial Registration: This protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) (registration number: CRD42013006960).

Background: Data on therapeutic interventions following deliberate self harm (DSH) in patients with treatment-resistant depression (TRD) are very scant and there is no unanimous consensus on the best pharmacological option for these patients. There is some evidence that lithium treatment might be effective in reducing the risk of completed suicide in adult patients with unipolar affective disorders, however no clear cut results have been found so far. The primary aim of the present study is to assess whether adding lithium to standard therapy is an effective treatment strategy to reduce the risk of suicidal behaviour in long term treatment of people with TRD and previous history of DSH., Methods/design: We will carry out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode will be allocated to add lithium to current therapy (intervention arm) or not (control arm). Following randomisation, treatment is to be taken daily for 1 year unless some clear reason to stop develops. Suicide completion and acts of DSH during the 12 months of follow-up will constitute the composite primary outcome. To preserve outcome assessor blindness, an independent adjudicating committee, blind to treatment allocation, will anonymously review all outcome events., Discussion: The results of this study should indicate whether lithium treatment is associated with lower risk of completed suicide and DSH in adult patients with treatment resistant unipolar depression, who recently attempted suicide., Trial Registration: ClinicalTrials.gov identifier: NCT00927550.

Introduction: In recent years the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology has often been used by international or national health authorities, or scientific societies, for developing evidence-based treatment recommendations. However, the GRADE approach has never been used by practicing physicians who aim at harmonizing their prescribing behaviours paying due attention to the best available evidence. This paper describes the experience of a working group of psychiatrists who adopted the GRADE approach to develop clinical recommendations on the use of psychotropic drugs in specialist mental healthcare., Case Description: The project was conducted in the Department of Mental Health of Verona, Italy, a city located in the north of Italy. At the beginning of 2012, psychiatrists with a specific interest in the rational use of psychotropic drugs were identified and appointed as members of a Guideline Development Group (GDG). The first task of the GDG was the identification of controversial areas in the use of psychotropic drugs, the definition of scoping questions, and the identification of outcomes of interest. The GDG was supported by a scientific secretariat, who searched the evidence, identified one or more systematic reviews matching the scoping questions, and drafted GRADE tables., Discussion and Evaluation: On the basis of efficacy, acceptability, tolerability and safety data, considering the risk of bias and confidence in estimates, and taking also into consideration preferences, values and practical aspects in favour and against the intervention under scrutiny, a draft recommendation with its strength was formulated and agreed by GDG members. Recommendations were submitted for consideration to all specialists of the Department, discussed in two plenary sessions open to the whole staff, and finally approved at the end of 2012., Conclusion: The present project of guideline development raised several challenging and innovating aspects, including a "bottom-up" approach, as it was motivated by reasons that found agreement among specialists, those who developed the recommendations were those who were supposed to follow them, and values, preferences and feasibility issues were considered paying due attention to local context variables.

Objective: To quantify schizophrenia trialling activity in African countries and to describe the main features of these trials., Methods: We searched the Cochrane Schizophrenia Group Register, which contains 16,000 citations to 13,000 studies relating only to people with schizophrenia or schizophrenia-like illness, to identify schizophrenia trials conducted in Africa without time limitation., Results: A total of 38 trials met the inclusion criteria and were included in our analysis. Of the 54 countries of Africa, only 8 produced at least one trial: South Africa produced the majority of trials (20 out of 38 trials, 53%), followed by Nigeria (7 out of 38 trials, 18%) and Egypt (4 out of 38 trials, 11%). The majority of studies investigated the efficacy of pharmacological interventions, were short in duration, and employed a double-blind design. The quality of reporting was generally poor. We found six trials comparing antipsychotics from the WHO Essential List of Medicine versus new generation antipsychotics. In terms of efficacy and acceptability, these studies failed to show any advantage of newer antipsychotics over first-generation agents., Conclusions: We observed an impressive mismatch between the number of individuals with schizophrenia living in African countries, estimated to be around 10 million, and the overall number of patients included in African trials, which is less than 2,000. These few trials were of low quality and appeared not to reflect the real needs of the population. We argue that the concept of pragmatism should be introduced into the design of randomized trials in African countries. Pragmatic trials should investigate whether treatments, given in real-world circumstances, really have clinically meaningful effects.

Background: A new resolution on mental, neurological and substance use disorders was adopted in January 2012 by the World Health Organization (WHO) Executive Board. The resolution urges WHO and Member States to collaborate in the development of a comprehensive mental health action plan, to be submitted for discussion and approval to the WHO World Health Assembly. This commentary aims at rising awareness on the risk that this resolution may not fulfil its potential., Discussion: Lack of political awareness and visibility of the resolution is a first major issue. Theoretically, Member States should be aware of the resolution and support its implementation at their respective national level, but in practice political commitment may not be high enough, and technical and financial resources made available may be limited. A second challenge is that the resolution suggests to work with Member States and technical agencies to promote academic exchange through which to contribute to policy-making in mental health. It is not straightforward, however, how such a statement may be effectively translated into action. A third key methodological aspect is how scientific evidence and factors other than scientific evidence will be handled. This seems particularly relevant in the field of mental health, where value-based decisions together with resource and feasibility considerations may be unavoidable., Summary: We argue that WHO and Member States should work together to increase the visibility of the resolution, ensuring that Ministries of Health and other relevant components of the health systems are aware of the resolution and its implications. As the resolution urges for academic exchange, WHO should develop a plan for an explicit, inclusive and open call for support and collaboration, so that partners willing to contribute are not kept out from the process. The production of an action plan for mental disorders should be based on scientifically sound methodology. Such a methodology should be transparently described, for example in a WHO process document, to make it clear how individual-level recommendations and policy-level guidance are developed. WHO should establish and maintain an open forum of experts, scientists, health officials and user groups worldwide to interact and agree on values, preferences, feasibility, acceptability, implementability, equity and economic issues that should inform the action plan.

Background: Well-designed and properly executed randomized controlled trials (RCTs) provide the best evidence on the efficacy of healthcare interventions. Mental health has a strong tradition of using trial to evaluate treatments, but the translation of research to clinical practice is not always easy. Even well-conducted trials do not necessarily address the needs of every day care and trials can reflect local needs and the specific culture in which they are undertaken. Generalizing results to other contexts can become problematic but these trials may, nevertheless, be very helpful within their own context. Moreover, pathways for drug approval can be different depending on local regulatory agencies. Local trials are helpful for decision-making in the region from which they come, but should not be viewed in isolation. National quantity and quality of trials may vary across nations.The aim of this study is to quantify trialing activity in Italy from 1948 until 2009 and to describe characteristics of these trials. In addition, we evaluated change over time in three keys aspects: sample size, follow-up duration, and number of outcomes., Methods: We used the Cochrane Schizophrenia Group's register that contains 16,000 citations to 13,000 studies relating only to people with schizophrenia or schizophrenia-like illness. Randomized controlled trials and controlled clinical trials undertaken in Italy and involving pharmacological interventions were included., Results: The original search identified 155 records of potentially eligible studies, 74 of which were excluded because do not meet inclusion criteria. A total of 81 studies were included in the analysis. The majority of trials were conducted in north Italy, and published in international journals between 1981 and 1995. The majority of studies (52 out of 81) used standardized diagnostic criteria for schizophrenia disorder. They were defined as randomized and used blind methods to administer treatment. However, most failed to report detail regarding methodological procedures and it is difficult to ascertain which studies are associated with a low risk of bias., Conclusions: Trials should be designed to address the needs of everyday care with the aim of following large samples of typical patients in the long term. The Italian tradition in the area of trialing treatments for people with schizophrenia is not as strong as in many other similar countries and Italy should be producing more, better, independent, and clinically relevant trials.

Background: This study aimed to investigate existing trialling activity relating to three antipsychotic drugs from the WHO List of Essential Medicines (chlorpromazine, fluphenazine decanoate, haloperidol), link existing trials to existing Cochrane reviews, identify gaps in reviewing activity on accessible treatments for people with schizophrenia., Methods: We used the Cochrane Schizophrenia Group's register searching for all studies comparing the three antipsychotic drugs with each other and with all other pharmacological interventions listed on the Essential Medicines List (with the addition of 'placebo or no drug'). For each we also considered studies that focussed on administration, dose, withdrawal and use of that drug in specific circumstances administration. Data were then extracted on a number of studies, number of participants within those studies, and as to whether a maintained review already exists. Finally, every effort was made to consider as to whether there were possibilities for missing comparisons that no one had ever investigated., Results: There has been considerable research activity involving the three 'essential' antipsychotics and also comparing those three drugs to others on the 'essential' list. We found 490 studies with 77957 participants for haloperidol, 316 studies with 29179 participants for chlorpromazine and 33 studies with 4503 participants for fluphenazine decanoate. Reviewing activity has also been considerable in this area but there are notable omissions which would necessitate new reviews to comprehensively cover the area., Conclusions: We have used the 'sample frame' of the WHO Essential drug list as a starting point. WHO prioritises for us those drugs that have universal accessibility but they may not be the compounds that are first choice if others are available. It is encouraging to see how many maintained reviews already exist to service those undertaking WHO guidelines. The needs of those guiding care can be taken as a means of prioritising research. For largest global impact WHO Essential Medicine list provides clear direction. By using this technique workload can be anticipated, prioritising can take place for new reviews and updates.

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.