Leave no one behind: rethinking policy and practice at the national level to prevent mental disorders

The global burden of mental disorders is increasing, in line with the shift from communicable to chronic non-communicable diseases. Mental disorders affect the functioning of individuals, resulting not only in enormous emotional suffering and diminished quality of life, but also in stigma and discrimination. This burden extends to the community and society, with far-reaching economic and social consequences. Even under optimal conditions, treatment alone will never be sufficient to reduce the global burden of mental disorders, so a shift in focus from treatment to prevention of mental disorders should be promoted at the central level in the form of legislation, policy formulation and resource allocation. Universal and selective prevention programs should be prioritized nationally, as they aim to change the risk profile of the entire population and specifically target populations at risk for mental disorders, respectively. In this article, we review the key risk factors for mental disorders and the measures that can be taken at the national level to prevent them, taking into due consideration that prevention efforts can vary based on the audience they are addressing, level of intensity they are providing, and the life phase they target. By adopting a human rights perspective and placing the social determinants of health at the center of our narrative, we maintain that improving mental health cannot be achieved by strengthening health services alone. Coordination across government departments is needed to implement multi-level public health interventions across a wide range of settings, programs, and policies. Focusing on children's mental health and addressing poverty, gender inequality and social discrimination should be absolute priorities for national mental health policies and plans

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

Psychological treatment of depression: a systematic overview of a 'Meta-Analytic Research Domain'

Background: Over the past 16 years, we have developed a 'Meta-analytic Research Domain' (MARD) of all randomized trials of psychological treatments of depression. A MARD is a living systematic review of a research field, that cannot be otherwise covered by one (network) meta-analysis and includes multiple PICOs. In this paper we give an overview of the findings of this MARD. Methods: A narrative review of the results of the 118 meta-analyses on psychotherapies for depression that were published within our MARD. Results: Most research has been conducted on cognitive-behavioral therapy (CBT), but several other psychotherapies are also effective, with few differences between therapies. They can be effectively delivered in individual, group, telephone and guided self-help format and are effective in many different target groups and across different age groups, although the effects are significantly smaller in children and adolescents. Psychotherapies have comparable effects as pharmacotherapy at the short term but are probably more effective at the longer term. Combined treatment is more effective than either psychotherapy or pharmacotherapy alone at the short, but also at the longer term. Limitations: We did not summarize all published meta-analyses (protocols, methodological studies) and have not compared our results to those found in other meta-analyses on comparable subjects. Conclusion: Psychotherapies can contribute considerably to a reduction of the disease burden of depression. MARDs are an important next step in the aggregation of knowledge from randomized controlled trials in psychological treatments of depression as well as in other healthcare sectors

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

Protocol for individual participant data meta-analysis of interventions for post-traumatic stress

Introduction: Several evidence-based treatments are effective for post-traumatic stress disorder (PTSD), yet a substantial proportion of patients do not respond or dropout of treatment. We describe the protocol for a systematic review and individual participant data meta-analysis (IPD-MA) aimed at assessing the effectiveness and adverse effects of psychotherapy and pharmacotherapy interventions for treating PTSD. Additionally, we seek to examine moderators and predictors of treatment outcomes. Method and analysis: This IPD-MA includes randomised controlled trials comparing psychotherapy and pharmacotherapy interventions for PTSD. PubMed, Embase, PsycINFO, PTSDpubs and CENTRAL will be screened up till the 11th of January 2021. The target population is adults with above-threshold baseline PTSD symptoms on any standardised self-report measure. Trials will only be eligible if at least 70% of the study sample have been diagnosed with PTSD by means of a structured clinical interview. The primary outcomes of this IPD-MA are PTSD symptom severity, and response rate. Secondary outcomes include treatment dropout and adverse effects. Two independent reviewers will screen major bibliographic databases and past reviews. Authors will be contacted to contribute their participant-level datasets. Datasets will be merged into a master dataset. A one-stage IPD-MA will be conducted focusing on the effects of psychological and pharmacological interventions on PTSD symptom severity, response rate, treatment dropout and adverse effects. Subsequent analyses will focus on examining the effect of moderators and predictors of treatment outcomes. These will include sociodemographic, treatment-related, symptom-related, resilience, intervention, trauma and combat-related characteristics. By determining the individual factors that influence the effectiveness of specific PTSD treatments, we will gain insight into personalised treatment options for PTSD. Ethics and dissemination: Specific ethics approval for an IPD-MA is not required as this study entails secondary analysis of existing anonymised data. The results of this study will be published in peer-reviewed scientific journals and presentations

Resilience of people with chronic medical conditions during the COVID-19 pandemic: a 1-year longitudinal prospective survey

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

Dismantling and personalising task-sharing psychosocial interventions for common mental disorders: a study protocol for an individual participant data component network meta-analysis.

INTRODUCTION Common mental disorders, including depression, anxiety and related somatic health symptoms, are leading causes of disability worldwide. Especially in low-resource settings, psychosocial interventions delivered by non-specialist providers through task-sharing modalities proved to be valid options to expand access to mental healthcare. However, such interventions are usually eclectic multicomponent interventions consisting of different combinations of evidence-based therapeutic strategies. Which of these various components (or combinations thereof) are more efficacious (and for whom) to reduce common mental disorder symptomatology is yet to be substantiated by evidence. METHODS AND ANALYSIS Comprehensive search was performed in electronic databases MEDLINE, Embase, PsycINFO and the Cochrane Register of Controlled Trials-CENTRAL from database inception to 15 March 2023 to systematically identify all randomised controlled trials that compared any single component or multicomponent psychosocial intervention delivered through the task-sharing modality against any active or inactive control condition in the treatment of adults suffering from common mental disorders. From these trials, individual participant data (IPD) of all measured outcomes and covariates will be collected. We will dismantle psychosocial interventions creating a taxonomy of components and then apply the IPD component network meta-analysis (IPD-cNMA) methodology to assess the efficacy of individual components (or combinations thereof) according to participant-level prognostic factors and effect modifiers. ETHICS AND DISSEMINATION Ethics approval is not applicable for this study since no original data will be collected. Results from this study will be published in peer-reviewed journals and presented at relevant conferences

Withdrawal Syndrome Following Discontinuation of 28 Antidepressants: Pharmacovigilance Analysis of 31,688 Reports from the WHO Spontaneous Reporting Database

Introduction: Evidence is lacking on withdrawal syndrome related to individual antidepressants and relevant risk factors for severe reactions. Objective: To ascertain whether antidepressants are associated with an increased reporting of withdrawal syndrome as compared with other medications, and to investigate risk factors for severe reactions. Methods: This is a case/non-case pharmacovigilance study, based on the VigiBase®, the WHO global database of individual case safety reports of suspected adverse drug reactions. We performed a disproportionality analysis of reports of antidepressant-related withdrawal syndrome (calculating reporting odds ratio [ROR] and Bayesian information component [IC]). We compared antidepressants to all other drugs, to buprenorphine (positive control), and to each other within each class of antidepressants (selective serotonin reuptake inhibitors [SSRIs], tricyclics and other antidepressants). Antidepressants with significant disproportionate reporting were ranked in terms of clinical priority. Serious versus non-serious reactions were compared. Results: There were 31,688 reports of antidepressant-related withdrawal syndrome were found. A disproportionate reporting was detected for 23 antidepressants. The estimated ROR for antidepressants altogether, compared to all other drugs, was 14.26 (95% CI 14.08-14.45), 17.01 for other antidepressants (95% CI 16.73-17.29), 13.65 for SSRIs (95% CI 13.41-13.90) and 2.8 for tricyclics (95% CI 2.59-3.02). Based on clinical priority ranking, the strongest disproportionate reporting was found for paroxetine, duloxetine, venlafaxine and desvenlafaxine, being comparable to buprenorphine. Withdrawal syndrome was reported as severe more often in males, adolescents, persons in polypharmacy, and with a longer antidepressant treatment duration (p < 0.05). Conclusions: Antidepressants are associated with an increased reporting of withdrawal syndrome compared with other drug classes. When prescribing and discontinuing antidepressants, clinicians should be aware of the potentially different proclivity of withdrawal syndrome across individual antidepressants, and the liability to experience more severe withdrawal symptoms in relation to specific patient characteristics

Which psychotherapy is effective in panic disorder? And which delivery formats are supported by the evidence? Study protocol for two systematic reviews and network meta-analyses

Introduction: Panic disorder is among the most prevalent anxiety diseases. Although psychotherapy is recommended as first-line treatment for panic disorder, little is known about the relative efficacy of different types of psychotherapies. Moreover, there is little evidence concerning the effectiveness of different formats of major psychotherapeutic types, such as cognitive-behavioural therapy (CBT). In this protocol, we present an overarching project consisting of two systematic reviews and network meta-analyses (NMA) to shed light on which psychotherapy (NMA-1), and specifically, which CBT delivery format (NMA-2) should be considered most effective for adults suffering from panic disorder with or without agoraphobia. Methods and analyses: Starting from a common pool of data, we will conduct two systematic reviews and NMA of randomised controlled trials examining panic disorder. A comprehensive search will be performed in electronic databases MEDLINE, Embase, PsycINFO and the Cochrane Register of Controlled Trials-CENTRAL from database inception to 1 January 2021 to identify relevant studies. A systematic approach to searching, screening, reviewing and data extraction will be applied. Titles, abstract and-whenever necessary-full texts will be examined independently by at least two reviewers. The quality of the included studies will be assessed using the revised Cochrane risk of bias tool V.2. The primary efficacy outcome will be anxiety symptoms at study endpoint. The primary acceptability outcome will be all-cause discontinuation, as measured by the proportion of patients who had discontinued treatment for any reason at endpoint. Data will be pooled using a random-effects model. Pairwise and NMA will be conducted. Ethics and dissemination: No ethical approval is necessary for these two studies, as there will be no collection of primary data. The results will be disseminated through peer-reviewed publications and presentations at national and international conferences and meetings