Antipsychotic-Related DRESS Syndrome: Analysis of Individual Case Safety Reports of the WHO Pharmacovigilance Database.

INTRODUCTION: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is gaining attention in pharmacovigilance, but its association with antipsychotics, other than clozapine, is still unclear. METHODS: We conducted a case/non-case study with disproportionality analysis based on the World Health Organization (WHO) global spontaneous reporting database, VigiBase®. We analyzed individual case safety reports of DRESS syndrome related to antipsychotics compared to (1) all other medications in VigiBase®, (2) carbamazepine (a known positive control), and (3) within classes (typical/atypical) of antipsychotics. We calculated reporting odds ratio (ROR) and Bayesian information component (IC), with 95% confidence intervals (CIs). Disproportionate reporting was prioritized based on clinical importance, according to predefined criteria. Additionally, we compared characteristics of patients reporting with serious/non-serious reactions. RESULTS: A total of 1534 reports describing DRESS syndrome for 19 antipsychotics were identified. The ROR for antipsychotics as a class as compared to all other medications was 1.0 (95% CI 0.9-1.1). We found disproportionate reporting for clozapine (ROR 2.3, 95% CI 2.1-2.5; IC 1.2, 95% CI 1.1-1.3), cyamemazine (ROR 2.3, 95% CI 1.5-3.5; IC 1.2, 95% CI 0.5-1.7), and chlorpromazine (ROR 1.5, 95% CI 1.1-2.1; IC 0.6, 95% CI 0.1-1.0). We found 35.7% of cases with co-reported anticonvulsants, and 25% with multiple concurrent antipsychotics in serious compared to 8.6% in non-serious cases (p = 0.03). Fatal cases were 164 (10.7%). CONCLUSIONS: Apart from the expected association with clozapine, chlorpromazine and cyamemazine (sharing an aromatic heteropolycyclic molecular structure) emerged with a higher-than-expected reporting of DRESS. Better knowledge of the antipsychotic-related DRESS syndrome should increase clinicians' awareness leading to safer prescribing of antipsychotics.

Scoping Review: Digital Mental Health Interventions for Children and Adolescents Affected by War.

OBJECTIVE: Over 200 million children and adolescents live in countries affected by violent conflict, are likely to have complex mental health needs, and struggle to access traditional mental health services. Digital mental health interventions have the potential to overcome some of the barriers in accessing mental health support. We performed a scoping review to map existing digital mental health interventions relevant for children and adolescents affected by war, examine the strength of the evidence base, and inform the development of future interventions. METHOD: Based on a pre-registered strategy, we systematically searched MEDLINE, Embase, Global Health, APA PsychInfo, and Google Scholar from the creation of each database to 30th September 2022, identifying k=6,843 studies. Our systematic search was complemented by extensive consultation with experts from the GROW Network. RESULTS: The systematic search identified 6 relevant studies: one evaluating digital mental health interventions for children and adolescents affected by war and five for those affected by disasters. Experts identified 35 interventions of possible relevance. The interventions spanned from universal prevention to specialist-guided treatment. Most interventions directly targeted young people and parents/carers and were self-guided. A quarter of the interventions were tested through randomized controlled trials. Because most interventions were not culturally or linguistically adapted to relevant contexts, their implementation potential was unclear. CONCLUSION: There is very limited evidence for the use of digital mental health interventions for children and adolescents affected by war at present. The review provides a framework to inform the development of new interventions.

Mapping the evidence on psychosocial interventions for migrant populations: Descriptive analysis of a living database of randomized studies.

Migrant mental health is a pressing public health issue with wide-ranging implications. Many randomized controlled trials (RCTs) have been conducted in this population to assess the effects of psychosocial interventions. However, the available evidence is characterized by controversy and fragmentation, with studies focusing on different migrant populations, interventions, outcomes, delivery modalities and settings. Aiming to promote systematic reviews of the effectiveness of psychosocial interventions in different migrant groups, we have developed a living database of existing RCTs. The development of the database provides an opportunity to map the existing RCT evidence in this population. A total of 135 studies involving 24,859 participants were included in the living database. The distribution of studies by year of publication aligns with the increasing global migrant population in recent years. Most studies focus primarily on adult participants, with a limited representation of children and adolescents, and a prevalence of female participants, which is consistent with epidemiological data, except for older adults, who are underrepresented in research. Studies predominantly focus on refugees and asylum seekers, likely due to their elevated risk of mental health issues, despite the substantial presence of economic migrants worldwide. While studies mainly involve migrants from the Middle East and East Asia, epidemiological data suggest a broader geographic representation, with migrants coming from Eastern Europe, Latin America and South Asia. The present descriptive analysis of RCTs on mental health and psychosocial interventions for migrant populations provides valuable insights into the existing research landscape. It should be used to inform future research efforts, ensuring that studies are more representative of the global migrant population and more responsive to the mental health needs of migrants in different contexts.

Tolerability of vortioxetine compared to selective serotonin reuptake inhibitors in older adults with major depressive disorder (VESPA): a randomised, assessor-blinded and statistician-blinded, multicentre, superiority trial.

Background: Major depressive disorder (MDD) is prevalent and disabling among older adults. Standing on its tolerability profile, vortioxetine might be a promising alternative to selective serotonin reuptake inhibitors (SSRIs) in such a vulnerable population. Methods: We conducted a randomised, assessor- and statistician-blinded, superiority trial including older adults with MDD. The study was conducted between 02/02/2019 and 02/22/2023 in 11 Italian Psychiatric Services. Participants were randomised to vortioxetine or one of the SSRIs, selected according to common practice. Treatment discontinuation due to adverse events after six months was the primary outcome, for which we aimed to detect a 12% difference in favour of vortioxetine. The study was registered in the online repository clinicaltrials.gov (NCT03779789). Findings: The intention-to-treat population included 179 individuals randomised to vortioxetine and 178 to SSRIs. Mean age was 73.7 years (standard deviation 6.1), and 264 participants (69%) were female. Of those on vortioxetine, 78 (44%) discontinued the treatment due to adverse events at six months, compared to 59 (33%) of those on SSRIs (odds ratio 1.56; 95% confidence interval 1.01-2.39). Adjusted and per-protocol analyses confirmed point estimates in favour of SSRIs, but without a significant difference. With the exception of the unadjusted survival analysis showing SSRIs to outperform vortioxetine, secondary outcomes provided results consistent with a lack of substantial safety and tolerability differences between the two arms. Overall, no significant differences emerged in terms of response rates, depressive symptoms and quality of life, while SSRIs outperformed vortioxetine in terms of cognitive performance. Interpretation: As opposed to what was previously hypothesised, vortioxetine did not show a better tolerability profile compared to SSRIs in older adults with MDD in this study. Additionally, hypothetical advantages of vortioxetine on depression-related cognitive symptoms might be questioned. The study's statistical power and highly pragmatic design allow for generalisability to real-world practice. Funding: The study was funded by the Italian Medicines Agency within the "2016 Call for Independent Drug Research".

Psychotherapies for Generalized Anxiety Disorder in Adults: A Systematic Review and Network Meta-Analysis of Randomized Clinical Trials.

Importance: Generalized anxiety disorder (GAD) is one of the most common mental disorders in adults. Psychotherapies are among the most recommended treatments for GAD, but which should be considered as first-line treatment needs to be clarified. Objective: To use a network meta-analysis to examine the short- and long-term associations of different psychotherapies with outcomes of effectiveness and acceptability in adults with GAD. Data Sources: MEDLINE, Embase, PsycINFO, and the Cochrane Register of Controlled Trials were searched from database inception to January 1, 2023, to identify randomized clinical trials (RCTs) of psychotherapies for adults with GAD. Study Selection: RCTs comparing any type of psychotherapy against another or with a control condition for the treatment of adults (≥18 years, both sexes) with a primary diagnosis of GAD were eligible for inclusion. Data Extraction and Synthesis: This study followed Cochrane standards for extracting data and assessing data quality and used the PRISMA guideline for reporting. Risk of bias of individual studies was assessed using the second version of the Cochrane risk of bias tool, and the Confidence in Network Meta-Analysis was used to rate the certainty of evidence for meta-analytical results. Main Outcomes and Measures: Eight psychotherapies were compared against one another and with 2 control conditions. Primary outcomes were severity of GAD symptoms and acceptability of the psychotherapies. Random-effects model pairwise and network meta-analyses were conducted. For effectiveness, standardized mean differences (SMDs) were pooled, and for acceptability, relative risks with 95% CIs were calculated. Results: Data from 65 RCTs were included. Effect size estimates on data from 5048 participants (mean [SD], 70.9% [11.9%] women; mean [SD] age, 42.2 [12.5] years) suggested that third-wave cognitive behavior therapies (CBTs) (SMD, -0.76 [95% CI, -1.15 to -0.36]; certainty, moderate), CBT (SMD, -0.74 [95% CI, -1.09 to -0.38]; certainty, moderate), and relaxation therapy (SMD, -0.59 [95% CI, -1.07 to -0.11]; certainty, low) were associated with reduced GAD symptoms vs treatment as usual. Relative risks for all-cause discontinuation (indication of acceptability) signaled no differences compared with treatment as usual for all psychotherapies (eg, relative risk, 1.04 [95% CI, 0.64-1.67] for CBT vs treatment as usual). When excluding studies at high risk of bias, relaxation therapy lost its superiority over treatment as usual (SMD, -0.47; 95% CI, -1.18 to 0.23). When considering anxiety severity at 3 to 12 months after completion of the intervention, only CBT remained significantly associated with greater effectiveness than treatment as usual (SMD, -0.60; 95% CI, -0.99 to -0.21). Conclusions and Relevance: Given the evidence in this systematic review and network meta-analysis for its associations with both acute and long-term effectiveness, CBT may represent the first-line therapy of GAD. Third-wave CBTs and relaxation therapy were associated with short-term effectiveness and may also be offered.

Umbrella Systematic Review and Meta-Analysis: Physical Activity as an Effective Therapeutic Strategy for Improving Psychosocial Outcomes in Children and Adolescents.

OBJECTIVE: Physical activity (PA) interventions are part of many interdisciplinary programs for the management of children and adolescents with or without physical or psychological conditions or disabilities. Aiming to summarize the available evidence, we conducted an umbrella review of meta-analyses of PA interventions that included psychosocial outcomes in populations of children and adolescents. METHOD: Literature searches were conducted in PubMed, Cochrane Central, Web of Science, Medline, SPORTDiscus, and PsychInfo from January 1, 2010, to May 6, 2022. Meta-analyses of randomized and quasi-randomized studies investigating the efficacy of PA interventions for psychosocial outcomes in children and adolescents were included. Summary effects were recalculated using common metric and random-effects models. We assessed between-study heterogeneity, predictive intervals, publication bias, small study effects, and whether the results of the observed positive studies were greater than expected due to chance. On the basis of these calculations, strength of associations was assessed using quantitative umbrella review criteria, and credibility of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Quality was assessed using the AMSTAR 2 tool. This study is registered with the Open Science Framework, https://osf.io/ap8qu. RESULTS: A total of 112 studies from 18 meta-analyses generating 12 new meta-analyses comprising 21,232 children and adolescents in population groups including attention-deficit/hyperactivity disorder, cancer, cerebral palsy, chronic respiratory diseases, depression, neuromotor impairment, and obesity and in general populations were included. PA interventions were efficacious in reducing psychological symptoms in all meta-analyses across the different population groups using random-effects models. However, umbrella review criteria suggested a weak strength of association for this outcome, and GRADE credibility of evidence ranged from moderate to very low. For psychological well-being, 3 out of 5 meta-analyses identified significant effects, but the strength of these associations was weak, and GRADE credibility of evidence ranged from moderate to very low. Similarly, for social outcomes, meta-analyses reported a significant summary effect, but the strength of association was weak, and GRADE credibility of evidence ranged from moderate to very low. For self-esteem, one meta-analysis in children with obesity failed to show any effect. CONCLUSION: Even though existing meta-analyses suggested a beneficial effect of PA interventions on psychosocial outcomes across different population groups, the strength of associations was weak, and the credibility of evidence was variable depending on the target population, outcome, and condition or disability. Randomized studies of PA interventions in children and adolescents with and without different physical and psychological conditions or disabilities should always include psychosocial outcomes as an important dimension of social and mental health. STUDY PREREGISTRATION INFORMATION: Prenatal Maternal Infection and Adverse Neurodevelopment: A Structural Equation Modelling Approach to Downstream Environmental Hits; https://osf.io/; ap8qu.

The WHO Mental Health Gap Action Programme for mental, neurological, and substance use conditions: the new and updated guideline recommendations.

The WHO Mental Health Gap Action Programme (mhGAP) guideline update reflects 15 years of investment in reducing the treatment gap and scaling up care for people with mental, neurological, and substance use (MNS) conditions. It was produced by a guideline development group and steering group, with support from topic experts, using quantitative and qualitative evidence and a systematic review of use of mhGAP. 90 recommendations from the 2015 guideline update were validated and endorsed for use in their current format. These are joined by 30 revised recommendations and 18 new recommendations, including a new module on anxiety. Psychological interventions are emphasised as treatments and digitally delivered interventions feature across many modules, as well as updated recommendations for psychotropic medicines. Research gaps identified include the need for evidence from low-resource settings and on the views of people with lived experience of MNS conditions. The revised recommendations ensure that mhGAP continues to offer high-quality, timely, transparent, and evidence-based guidance to support non-specialist health workers in low-income and middle-income countries in providing care to individuals with MNS conditions.

Implementation outcomes in psychosocial intervention studies for children and adolescents living in low- and middle-income countries: A systematic review.

Psychosocial interventions play a key role in addressing mental health and substance use needs for children and adolescents living in low- and middle-income countries (LMICs). While research efforts have primarily focused on their effectiveness, implementation outcomes also require examining. We conducted a systematic review of qualitative, quantitative, and mixed-methods studies (PROSPERO: CRD42022335997) to synthesize the literature on implementation outcomes for psychosocial interventions for children and adolescents in LMICs. We searched Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Web of Science, PsychINFO, and Global Health through April 2023. Data were extracted and quality appraised through the Mixed Methods Appraisal Tool (MMAT) independently by two reviewers. A total of 13,380 records were screened, and 87 studies met inclusion criteria. Feasibility was the most reported implementation outcome (69, 79%), followed by acceptability (60, 69%), and fidelity (32, 37%). Appropriateness was assessed in 11 studies (13%), implementation costs in 10 (11%), and sustainability in one (1%). None of the included studies reported on penetration or adoption. Despite a growing body of evidence for implementation research in child and adolescent global mental health, most research focused on earlier-stage implementation outcomes, assessing them in research-controlled settings. To overcome this, future efforts should focus on assessing interventions in routine care, assessing later-stage implementation outcomes through standardized tools.

An umbrella review of candidate predictors of response, remission, recovery, and relapse across mental disorders.

We aimed to identify diagnosis-specific/transdiagnostic/transoutcome multivariable candidate predictors (MCPs) of key outcomes in mental disorders. We conducted an umbrella review (protocol  link ), searching MEDLINE/Embase (19/07/2022), including systematic reviews of studies reporting on MCPs of response, remission, recovery, or relapse, in DSM/ICD-defined mental disorders. From published predictors, we filtered MCPs, validating MCP criteria. AMSTAR2/PROBAST measured quality/risk of bias of systematic reviews/individual studies. We included 117 systematic reviews, 403 studies, 299,888 individuals with mental disorders, testing 796 prediction models. Only 4.3%/1.2% of the systematic reviews/individual studies were at low risk of bias. The most frequently targeted outcome was remission (36.9%), the least frequent was recovery (2.5%). Studies mainly focused on depressive (39.4%), substance-use (17.9%), and schizophrenia-spectrum (11.9%) disorders. We identified numerous MCPs within disorders for response, remission and relapse, but none for recovery. Transdiagnostic MCPs of remission included lower disease-specific symptoms (disorders = 5), female sex/higher education (disorders = 3), and quality of life/functioning (disorders = 2). Transdiagnostic MCPs of relapse included higher disease-specific symptoms (disorders = 5), higher depressive symptoms (disorders = 3), and younger age/higher anxiety symptoms/global illness severity/ number of previous episodes/negative life events (disorders = 2). Finally, positive trans-outcome MCPs for depression included less negative life events/depressive symptoms (response, remission, less relapse), female sex (response, remission) and better functioning (response, less relapse); for schizophrenia, less positive symptoms/higher depressive symptoms (remission, less relapse); for substance use disorder, marital status/higher education (remission, less relapse). Male sex, younger age, more clinical symptoms and comorbid mental/physical symptoms/disorders were poor prognostic factors, while positive factors included social contacts and employment, absent negative life events, higher education, early access/intervention, lower disease-specific and comorbid mental and physical symptoms/conditions, across mental disorders. Current data limitations include high risk of bias of studies and extraction of single predictors from multivariable models. Identified MCPs can inform future development, validation or refinement of prediction models of key outcomes in mental disorders.

Pharmacological treatments in panic disorder in adults: a network meta-analysis.

BACKGROUND: A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as racing heart, chest pain, sweating, shaking, dizziness, flushing, churning stomach, faintness and breathlessness. Other recognised panic attack symptoms involve fearful cognitions, such as the fear of collapse, going mad or dying, and derealisation (the sensation that the world is unreal). Panic disorder is common in the general population with a prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions, including antidepressants and benzodiazepines. OBJECTIVES: To compare, via network meta-analysis, individual drugs (antidepressants and benzodiazepines) or placebo in terms of efficacy and acceptability in the acute treatment of panic disorder, with or without agoraphobia. To rank individual active drugs for panic disorder (antidepressants, benzodiazepines and placebo) according to their effectiveness and acceptability. To rank drug classes for panic disorder (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), mono-amine oxidase inhibitors (MAOIs) and benzodiazepines (BDZs) and placebo) according to their effectiveness and acceptability. To explore heterogeneity and inconsistency between direct and indirect evidence in a network meta-analysis. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Specialised Register, CENTRAL, CDSR, MEDLINE, Ovid Embase and PsycINFO to 26 May 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of people aged 18 years or older of either sex and any ethnicity with clinically diagnosed panic disorder, with or without agoraphobia. We included trials that compared the effectiveness of antidepressants and benzodiazepines with each other or with a placebo. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles/abstracts and full texts, extracted data and assessed risk of bias. We analysed dichotomous data and continuous data as risk ratios (RRs), mean differences (MD) or standardised mean differences (SMD): response to treatment (i.e. substantial improvement from baseline as defined by the original investigators: dichotomous outcome), total number of dropouts due to any reason (as a proxy measure of treatment acceptability: dichotomous outcome), remission (i.e. satisfactory end state as defined by global judgement of the original investigators: dichotomous outcome), panic symptom scales and global judgement (continuous outcome), frequency of panic attacks (as recorded, for example, by a panic diary; continuous outcome), agoraphobia (dichotomous outcome). We assessed the certainty of evidence using threshold analyses. MAIN RESULTS: Overall, we included 70 trials in this review. Sample sizes ranged between 5 and 445 participants in each arm, and the total sample size per study ranged from 10 to 1168. Thirty-five studies included sample sizes of over 100 participants. There is evidence from 48 RCTs (N = 10,118) that most medications are more effective in the response outcome than placebo. In particular, diazepam, alprazolam, clonazepam, paroxetine, venlafaxine, clomipramine, fluoxetine and adinazolam showed the strongest effect, with diazepam, alprazolam and clonazepam ranking as the most effective. We found heterogeneity in most of the comparisons, but our threshold analyses suggest that this is unlikely to impact the findings of the network meta-analysis. Results from 64 RCTs (N = 12,310) suggest that most medications are associated with either a reduced or similar risk of dropouts to placebo. Alprazolam and diazepam were associated with a lower dropout rate compared to placebo and were ranked as the most tolerated of all the medications examined. Thirty-two RCTs (N = 8569) were included in the remission outcome. Most medications were more effective than placebo, namely desipramine, fluoxetine, clonazepam, diazepam, fluvoxamine, imipramine, venlafaxine and paroxetine, and their effects were clinically meaningful. Amongst these medications, desipramine and alprazolam were ranked highest. Thirty-five RCTs (N = 8826) are included in the continuous outcome reduction in panic scale scores. Brofaromine, clonazepam and reboxetine had the strongest reductions in panic symptoms compared to placebo, but results were based on either one trial or very small trials. Forty-one RCTs (N = 7853) are included in the frequency of panic attack outcome. Only clonazepam and alprazolam showed a strong reduction in the frequency of panic attacks compared to placebo, and were ranked highest. Twenty-six RCTs (N = 7044) provided data for agoraphobia. The strongest reductions in agoraphobia symptoms were found for citalopram, reboxetine, escitalopram, clomipramine and diazepam, compared to placebo. For the pooled intervention classes, we examined the two primary outcomes (response and dropout). The classes of medication were: SSRIs, SNRIs, TCAs, MAOIs and BDZs. For the response outcome, all classes of medications examined were more effective than placebo. TCAs as a class ranked as the most effective, followed by BDZs and MAOIs. SSRIs as a class ranked fifth on average, while SNRIs were ranked lowest. When we compared classes of medication with each other for the response outcome, we found no difference between classes. Comparisons between MAOIs and TCAs and between BDZs and TCAs also suggested no differences between these medications, but the results were imprecise. For the dropout outcome, BDZs were the only class associated with a lower dropout compared to placebo and were ranked first in terms of tolerability. The other classes did not show any difference in dropouts compared to placebo. In terms of ranking, TCAs are on average second to BDZs, followed by SNRIs, then by SSRIs and lastly by MAOIs. BDZs were associated with lower dropout rates compared to SSRIs, SNRIs and TCAs. The quality of the studies comparing antidepressants with placebo was moderate, while the quality of the studies comparing BDZs with placebo and antidepressants was low. AUTHORS' CONCLUSIONS: In terms of efficacy, SSRIs, SNRIs (venlafaxine), TCAs, MAOIs and BDZs may be effective, with little difference between classes. However, it is important to note that the reliability of these findings may be limited due to the overall low quality of the studies, with all having unclear or high risk of bias across multiple domains. Within classes, some differences emerged. For example, amongst the SSRIs paroxetine and fluoxetine seem to have stronger evidence of efficacy than sertraline. Benzodiazepines appear to have a small but significant advantage in terms of tolerability (incidence of dropouts) over other classes.

Understanding the protective effect of social support on depression symptomatology from a longitudinal network perspective.

BACKGROUND: Higher social support protects people from developing mental disorders. Limited evidence is available on the mechanism through which social support plays this protective role. OBJECTIVE: To investigate the stress-buffering process of social support on depressive symptoms using a novel longitudinal dynamic symptom network approach. METHODS: A total of 4242 adult participants who completed the first two waves (from May to October 2020) of the International Covid Mental Health Survey were included in the study. Cross-lagged panel network modelling was used to estimate a longitudinal network of self-reported social support, loneliness and depressive symptoms. Standardised regression coefficients from regularised cross-lagged regressions were estimated as edge weights of the network. FINDINGS: The results support a unidirectional protective effect of social support on key depressive symptoms, partly mediated through loneliness: A higher number of close confidants and accessible practical help was associated with decreased anhedonia (weight=-0.033) and negative self-appraisal symptoms (weight=-0.038). Support from others was also negatively associated with loneliness, which in turn associated with decreased depressed mood (weight=0.086) and negative self-appraisal (weight=0.077). We identified a greater number of direct relationships from social support to depressive symptoms among men compared with women. Also, the edge weights from social support to depression were generally stronger in the men's network. CONCLUSIONS: Reductions in negative self-appraisal might function as a bridge between social support and other depressive symptoms, and, thus, it may have amplified the protective effect of social support. Men appear to benefit more from social support than women. CLINICAL IMPLICATIONS: Building community-based support networks to deliver practical support, and loneliness reduction components are critical for depression prevention interventions after stressful experiences.

Addressing mental health problems among persons without stable housing in the context of the COVID-19 pandemic: study protocol for a randomised trial. RESPOND - France.

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.

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.

Effectiveness of a scalable, remotely delivered stepped-care intervention to reduce symptoms of psychological distress among Polish migrant workers in the Netherlands: study protocol for the RESPOND randomised controlled trial.

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.

Caregiver skills training for caregivers of individuals with neurodevelopmental disorders: A systematic review and meta-analysis.

AIM: To systematically review the effectiveness of caregiver and parent skills training programs, including caregiver-mediated interventions, for caregivers of individuals with neurodevelopmental disorders. METHOD: We conducted a systematic review with a random-effects meta-analysis. We searched 11 electronic databases through July 2021 and used a snowball methodology to locate relevant articles of randomized controlled trials. Effect size estimates were pooled using Hedges' g from data extracted from study reports and through author requests using random-effects meta-analyses for three child outcome categories (child development, adaptive behavior, and problem behavior) and three caregiver outcome categories (parenting skills and knowledge, psychological well-being, and interpersonal family relations). RESULTS: We located 44 910 records, from which 75 randomized controlled trials involving 4746 individuals with neurodevelopmental disorders and their caregivers were included. Random-effects meta-analyses showed improvements in child development (g = 0.30; 99% confidence interval [CI] = 0.07-0.53) and reduction in reported problem behaviors (g = 0.41; 99% CI = 0.24-0.59), but not a statistically significant improvement in adaptive behavior (g = 0.28; 99% CI = -0.42 to 0.98). Caregivers showed improvements in parenting skills and knowledge (g = 0.72; 99% CI = 0.53-0.90), psychological well-being (g = 0.52; 99% CI = 0.34-0.71), and interpersonal family relations (g = 0.76; 99% CI = 0.32-1.20). INTERPRETATION: Caregiver skills training programs benefit both caregivers and children with neurodevelopmental disorders. Skills training programs improve child development and behavior, improve parenting skills, reduce caregiver mental health issues, and improve family functioning. Programs using culturally appropriate training material to improve the development, functioning, and participation of children within families and communities should be considered when caring for children with neurodevelopmental disorders.

Primary-level and community worker interventions for the prevention of mental disorders and the promotion of well-being in low- and middle-income countries.

BACKGROUND: There is a significant research gap in the field of universal, selective, and indicated prevention interventions for mental health promotion and the prevention of mental disorders. Barriers to closing the research gap include scarcity of skilled human resources, large inequities in resource distribution and utilization, and stigma. OBJECTIVES: To assess the effectiveness of delivery by primary workers of interventions for the promotion of mental health and universal prevention, and for the selective and indicated prevention of mental disorders or symptoms of mental illness in low- and middle-income countries (LMICs). To examine the impact of intervention delivery by primary workers on resource use and costs. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, Global Index Medicus, PsycInfo, WHO ICTRP, and ClinicalTrials.gov from inception to 29 November 2021. SELECTION CRITERIA: Randomized controlled trials (RCTs) of primary-level and/or community health worker interventions for promoting mental health and/or preventing mental disorders versus any control conditions in adults and children in LMICs. DATA COLLECTION AND ANALYSIS: Standardized mean differences (SMD) or mean differences (MD) were used for continuous outcomes, and risk ratios (RR) for dichotomous data, using a random-effects model. We analyzed data at 0 to 1, 1 to 6, and 7 to 24 months post-intervention. For SMDs, 0.20 to 0.49 represented small, 0.50 to 0.79 moderate, and ≥ 0.80 large clinical effects. We evaluated the risk of bias (RoB) using Cochrane RoB2. MAIN RESULTS: Description of studies We identified 113 studies with 32,992 participants (97 RCTs, 19,570 participants in meta-analyses) for inclusion. Nineteen RCTs were conducted in low-income countries, 27 in low-middle-income countries, 2 in middle-income countries, 58 in upper-middle-income countries and 7 in mixed settings. Eighty-three RCTs included adults and 30 RCTs included children. Cadres of primary-level workers employed primary care health workers (38 studies), community workers (71 studies), both (2 studies), and not reported (2 studies). Interventions were universal prevention/promotion in 22 studies, selective in 36, and indicated prevention in 55 RCTs. Risk of bias The most common concerns over risk of bias were performance bias, attrition bias, and reporting bias. Intervention effects 'Probably', 'may', or 'uncertain' indicates 'moderate-', 'low-', or 'very low-'certainty evidence. *Certainty of the evidence (using GRADE) was assessed at 0 to 1 month post-intervention as specified in the review protocol. In the abstract, we did not report results for outcomes for which evidence was missing or very uncertain. Adults Promotion/universal prevention, compared to usual care: - probably slightly reduced anxiety symptoms (MD -0.14, 95% confidence interval (CI) -0.27 to -0.01; 1 trial, 158 participants) - may slightly reduce distress/PTSD symptoms (SMD -0.24, 95% CI -0.41 to -0.08; 4 trials, 722 participants) Selective prevention, compared to usual care: - probably slightly reduced depressive symptoms (SMD -0.69, 95% CI -1.08 to -0.30; 4 trials, 223 participants) Indicated prevention, compared to usual care: - may reduce adverse events (1 trial, 547 participants) - probably slightly reduced functional impairment (SMD -0.12, 95% CI -0.39 to -0.15; 4 trials, 663 participants) Children Promotion/universal prevention, compared to usual care: - may improve the quality of life (SMD -0.25, 95% CI -0.39 to -0.11; 2 trials, 803 participants) - may reduce adverse events (1 trial, 694 participants) - may slightly reduce depressive symptoms (MD -3.04, 95% CI -6 to -0.08; 1 trial, 160 participants) - may slightly reduce anxiety symptoms (MD -2.27, 95% CI -3.13 to -1.41; 1 trial, 183 participants) Selective prevention, compared to usual care: - probably slightly reduced depressive symptoms (SMD 0, 95% CI -0.16 to -0.15; 2 trials, 638 participants) - may slightly reduce anxiety symptoms (MD 4.50, 95% CI -12.05 to 21.05; 1 trial, 28 participants) - probably slightly reduced distress/PTSD symptoms (MD -2.14, 95% CI -3.77 to -0.51; 1 trial, 159 participants) Indicated prevention, compared to usual care: - decreased slightly functional impairment (SMD -0.29, 95% CI -0.47 to -0.10; 2 trials, 448 participants) - decreased slightly depressive symptoms (SMD -0.18, 95% CI -0.32 to -0.04; 4 trials, 771 participants) - may slightly reduce distress/PTSD symptoms (SMD 0.24, 95% CI -1.28 to 1.76; 2 trials, 448 participants). AUTHORS' CONCLUSIONS: The evidence indicated that prevention interventions delivered through primary workers - a form of task-shifting - may improve mental health outcomes. Certainty in the evidence was influenced by the risk of bias and by substantial levels of heterogeneity. A supportive network of infrastructure and research would enhance and reinforce this delivery modality across LMICs.

Association between adverse childhood experiences and suicidal behavior in schizophrenia spectrum disorders: A systematic review and meta-analysis.

Assessing and managing suicide behaviors is highly relevant to individuals with schizophrenia spectrum disorders. Our study aims to assess the association between adverse childhood experiences and suicidal behaviors in individuals with schizophrenia spectrum disorders. We included observational studies comparing the probability of suicide behaviors in adults with schizophrenia spectrum disorders exposed and unexposed to adverse childhood experiences. Odds ratio estimates were obtained by pooling data using a random-effects pairwise meta-analysis. Standardized criteria were used to assess the strength of the association of the pooled estimate. We found 21 eligible studies reporting outcomes for 6257 individuals from 11 countries. The primary outcome revealed an association between any suicidal behavior and adverse childhood experiences, which resulted "highly suggestive" according to validated Umbrella Criteria. Similarly, a positive association was confirmed for suicidal ideation and suicide attempt and for any subtype of adverse childhood experience. This meta-analysis showed that exposure to adverse childhood experiences strongly increases the probability of suicide behaviors in people with schizophrenia spectrum disorders.