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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 depress

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 chi

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

In this prospective study, we assessed the effectiveness and acceptability of paliperidone palmitate 1-month (PP1M) and aripiprazole monohydrate (AM) over 1-year follow-up. We included 195 subjects (117 treated with PP1M and 78 with AM) with schizophrenia spectrum disorders from real-world settings. We estimated no differences in hospitalization (Odds Ratio=1.59; p = 0.12), symptoms improvement (p = 0.90 adjusted for baseline severity), and discontinuation (Hazard Ratio=0.72; p = 0.20) at study endpoint. Although current evidence suggests the possible superiority of AM over PP1M, our findings showed comparable effectiveness between these drugs. Additional studies in real-world settings with direct comparisons between these two LAIs are needed.

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 adhere

Introduction Long-acting injectable (LAI) antipsychotics are prescribed to people with severe psychiatric disorders who show poor adherence to oral medication. The present paper examined factors potentially associated with medication adherence to LAI treatment. Methods The STAR (Servizi Territoriali Associati per la Ricerca) Network Depot Study was a multicenter, observational, prospective study that enrolled 461 subjects initiating a LAI from 32 Italian centers. After 6 and 12 months of treatment, we evaluated differences between participants with high (≥5 points) and low (<5 points) medication adherence using Kemp's 7-point scale in sociodemographic, clinical, psychopathological, and drug-related variables. Factors that differed significantly between the two groups were entered for multivariate logistic regression. Results Six months after enrollment, participants with high medication adherence were younger, living with other people, had lower Brief Psychiatric Rating Scale (BPRS) total scores, lower adverse events, and a more positive attitude toward medication than participants with low adherence. Multivariate regression confirmed lower BPRS resistance and activation scores, absence of adverse events, and positive attitude toward medication as factors significantly associated with good adherence. After 12 months, all BPRS subscales were significantly lower in the high adherence group, which also showed a more positive attitude toward medication. BPRS resistance and attitude toward medication were confirmed as factors associated with medication adherence. Discussion Our findings suggest that adherence to LAI is principally related to attitude toward medication and traits of suspiciousness/hostility. Quality of patient-clinician relationship and tailored psychoeducational strategies may positively affect adherence in people undergoing psychopharmacological treatment, including LAI.

01 februari 2023, Item does not contain fulltext, Neurodevelopmental disorders - including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disability, motor disorders, specific learning disorders, and tic disorders - manifest themselves early in development. Valid, reliable and broadly usable biomarkers supporting a timely diagnosis of these disorders would be highly relevant from a clinical and public health standpoint. We conducted the first systematic review of studies on candidate diagnostic biomarkers for these disorders in children and adolescents. We searched Medline and Embase + Embase Classic with terms relating to biomarkers until April 6, 2022, and conducted additional targeted searches for genome-wide association studies (GWAS) and neuroimaging or neurophysiological studies carried out by international consortia. We considered a candidate biomarker as promising if it was reported in at least two independent studies providing evidence of sensitivity and specificity of at least 80%. After screening 10,625 references, we retained 780 studies (374 biochemical, 203 neuroimaging, 133 neurophysiological and 65 neuropsychological studies, and five GWAS), including a total of approximately 120,000 cases and 176,000 controls. While the majority of the studies focused simply on associations, we could not find any biomarker for which there was evidence - from two or more studies from independent research groups, with results going into the same direction - of specificity and sensitivity of at least 80%. Other important metrics to assess the validity of a candidate biomarker, such as positive predictive value and negative predictive value, were infrequently reported. Limitations of the currently available studies include mostly small sample size, heterogeneous approaches and candidate biomarker targets, undue focus on single instead of joint biomarker signatures, and incomplete accounting for potential confounding factors. Future multivariable and mult

Long-acting injectable (LAI) antipsychotics are often used for the long-term management also of bipolar disorder (BD). Nonetheless, evidence on their effect on pragmatic outcomes such as hospitalization risk in BD is inconsistent. We carried out a mirror-image study comparing rates and number of days of hospitalization, one year before and after the initiation of LAI treatment, in a sample of subjects with BD. Participants were selected from the STAR Network Depot Study, a pragmatic, observational, multicenter research involving a cohort of inpatients and outpatients consecutively started on LAI treatment. Variations in rates and in total number of days of hospitalization between the 12 months before and those after treatment initiation were analyzed. Among 461 individuals screened for eligibility, we included 71 adults with BD, initiated either on first- (FGA) or second-generation (SGA) LAIs. We found a significant decrease in terms of 12-month hospitalization rates (p < 0.001) and number of days (p < 0.001) after LAI initiation, without any effect by age, gender, alcohol/substance use disorders, and symptom severity. Subgroup analyses based on antipsychotic class, history of LAI treatment, and concomitant oral medications, confirmed the decreasing trend on both hospitalization rates and number of days. However, these reductions were not significant among participants who continued this treatment for less than 6 months. Comprehensively, this study supports the role of LAIs as effective maintenance treatment options for BD. Further research is needed to identify clinical characteristics of people with BD who would most benefit from long-acting formulations of antipsychotics.

Background: Evidence on neonatal withdrawal syndrome following antidepressant intrauterine exposure is limited, particularly for antidepressants other than selective serotonin reuptake inhibitor (SSRIs). Methods: In our case/non-case pharmacovigilance study, based on VigiBase®, the WHO database of suspected adverse drug reactions, we estimated reporting odds ratio (ROR) and the Bayesian information component (IC) with 95% confidence/credibility intervals (CI) as measures of disproportionate reporting of antidepressant-related neonatal withdrawal syndrome. Antidepressants were first compared to all other medications, then to methadone, and finally within each class of antidepressants: SSRIs, tricyclics (TCA) and other antidepressants. Antidepressants were ranked in terms of clinical priority, based on semiquantitative score ratings. Serious v. non-serious reports were compared. Results: A total of 406 reports of neonatal withdrawal syndrome in 379 neonates related to 15 antidepressants were included. Disproportionate reporting was detected for antidepressants as a group as compared to all other drugs (ROR: 6.18, 95% CI 5.45-7.01, IC: 2.07, 95% CI 1.92-2.21). Signals were found for TCAs (10.55, 95% CI 8.02-13.88), followed by other antidepressants (ROR: 5.90, 95% CI 4.74-7.36) and SSRIs (ROR: 4.68, 95% CI 4.04-5.42). Significant disproportionality emerged for all individual antidepressants except for bupropion, whereas no disproportionality for any antidepressant was detected v. methadone. Eleven antidepressants had a moderate clinical priority score and four had a weak one. Most frequent symptoms included respiratory symptoms (n = 106), irritability/agitation (n = 75), tremor (n = 52) and feeding problems (n = 40). Conclusions: Most antidepressants are associated with moderate signals of disproportionate reporting for neonatal withdrawal syndrome, which should be considered when prescribing an antidepressant during pregnancy, irrespective of class. Keywords: Abstinen

Background: Long-acting injectable (LAI) antipsychotics are efficacious in managing psychotic symptoms in people affected by severe mental disorders, such as schizophrenia and bipolar disorder. The present study aimed to investigate whether attitude toward treatment and treatment adherence represent predictors of symptoms changes over time. Methods: The STAR Network “Depot Study” was a naturalistic, multicenter, observational, prospective study that enrolled people initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centers were assessed at three time points: baseline, 6-month, and 12-month follow-up. Psychopathological symptoms, attitude toward medication and treatment adherence were measured using the Brief Psychiatric Rating Scale (BPRS), the Drug Attitude Inventory (DAI-10) and the Kemp's 7-point scale, respectively. Linear mixed-effects models were used to evaluate whether attitude toward medication and treatment adherence independently predicted symptoms changes over time. Analyses were conducted on the overall sample and then stratified according to the baseline severity (BPRS < 41 or BPRS ≥ 41). Results: We included 461 participants of which 276 were males. The majority of participants had received a primary diagnosis of a schizophrenia spectrum disorder (71.80%) and initiated a treatment with a second-generation LAI (69.63%). BPRS, DAI-10, and Kemp's scale scores improved over time. Six linear regressions—conducted considering the outcome and predictors at baseline, 6-month, and 12-month follow-up independently—showed that both DAI-10 and Kemp's scale negatively associated with BPRS scores at the three considered time points. Linear mixed-effects models conducted on the overall sample did not show any significant association between attitude toward medication or treatment adherence and changes in psychiatric symptoms over time. However, after stratification according to baseline severity, we foun

Background: Recent guidelines suggested a wider use of long-acting injectable antipsychotics (LAI) than previously, but naturalistic data on the consequences of LAI use in terms of discontinuation rates and associated factors are still sparse, making it hard for clinicians to be informed on plausible treatment courses. Objective: Our objective was to assess, under real-world clinical circumstances, LAI discontinuation rates over a period of 12 months after a first prescription, reasons for discontinuation, and associated factors. Methods: The STAR Network ‘Depot Study’ was a naturalistic, multicentre, observational prospective study that enrolled subjects initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centres were assessed at baseline and at 6 and 12 months of follow-up. Psychopathology, drug attitude and treatment adherence were measured using the Brief Psychiatric Rating Scale, the Drug Attitude Inventory and the Kemp scale, respectively. Results: The study followed 394 participants for 12 months. The overall discontinuation rate at 12 months was 39.3% (95% confidence interval [CI] 34.4–44.3), with paliperidone LAI being the least discontinued LAI (33.9%; 95% CI 25.3–43.5) and olanzapine LAI the most discontinued (62.5%; 95% CI 35.4–84.8). The most frequent reason for discontinuation was onset of adverse events (32.9%; 95% CI 25.6–40.9) followed by participant refusal of the medication (20.6%; 95% CI 14.6–27.9). Medication adherence at baseline was negatively associated with discontinuation risk (hazard ratio [HR] 0.853; 95% CI 0.742–0.981; p = 0.026), whereas being prescribed olanzapine LAI was associated with increased discontinuation risk compared with being prescribed paliperidone LAI (HR 2.156; 95% CI 1.003–4.634; p = 0.049). Conclusions: Clinicians should be aware that LAI discontinuation is a frequent occurrence. LAI choice should be carefully discussed with the patient, tak

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 2016/6

This study, based on the 'Servizi Territoriali Associati per la Ricerca' (STAR) Network Depot Study nationwide baseline data, explored whether individual symptoms severity and clusters might influence the prescription of paliperidone palmitate 1-month (PP1M) vs. aripiprazole monohydrate. The Brief Psychiatric Rating Scale (BPRS) was used to assess psychopathology and relevant symptoms clusters. Drug Attitude Inventory, 10 items, was used to test attitude towards medications. Adherence to treatments was rated according to the Kemp seven-point scale. We assessed for eligibility 451 individuals and, among them, we included 195 subjects (n = 117 who started PPM1 and n = 78 aripiprazole monohydrate). Individuals were comparable in terms of age, gender, treatment years, recent hospitalizations, previous long-acting injectable antipsychotic treatments, additional oral treatments, attitude toward drugs, medication adherence, and alcohol/substance-related comorbidities. Subjects starting PP1M presented higher BPRS overall (P = 0.009), positive (P = 0.015), and negative (P = 0.010) symptom scores compared to subjects starting aripiprazole monohydrate. Results were confirmed by appropriate regression models and propensity score matching analysis. No differences were found comparing the other BPRS subscale scores: affect, resistance, and activation. Clinicians may be more prone to prescribe PPM1, rather than aripiprazole monohydrate, to subjects showing higher overall symptom severity, including positive and negative symptoms. No additional clinical factors influenced prescribing attitudes in our sample.

Aims: As refugees and asylum seekers are at high risk of developing mental disorders, we assessed the effectiveness of Self-Help Plus (SH +), a psychological intervention developed by the World Health Organization, in reducing the risk of developing any mental disorders at 12-month follow-up in refugees and asylum seekers resettled in Western Europe. Methods: Refugees and asylum seekers with psychological distress (General Health Questionnaire-12 ≥ 3) but without a mental disorder according to the Mini International Neuropsychiatric Interview (M.I.N.I.) were randomised to either SH + or enhanced treatment as usual (ETAU). The frequency of mental disorders at 12 months was measured with the M.I.N.I., while secondary outcomes included self-identified problems, psychological symptoms and other outcomes. Results: Of 459 participants randomly assigned to SH + or ETAU, 246 accepted to be interviewed at 12 months. No difference in the frequency of any mental disorders was found (relative risk [RR] = 0.841; 95% confidence interval [CI] 0.389-1.819; p-value = 0.659). In the per protocol (PP) population, that is in participants attending at least three group-based sessions, SH + almost halved the frequency of mental disorders at 12 months compared to ETAU, however so few participants and events contributed to this analysis that it yielded a non-significant result (RR = 0.528; 95% CI 0.180-1.544; p-value = 0.230). SH + was associated with improvements at 12 months in psychological distress (p-value = 0.004), depressive symptoms (p-value = 0.011) and wellbeing (p-value = 0.001). Conclusions: The present study failed to show any long-term preventative effect of SH + in refugees and asylum seekers resettled in Western European countries. Analysis of the PP population and of secondary outcomes provided signals of a potential effect of SH + in the long-term, which would suggest the value of exploring the effects of booster sessions and strategies to increase SH + adherence.

Importance: The cost-effectiveness of the Self-Help Plus (SH+) program, a group-based, guided, self-help psychological intervention developed by the World Health Organization for people affected by adversity, is unclear. Objective: To investigate the cost-utility of providing the SH+ intervention combined with enhanced usual care vs enhanced usual care alone for Syrian refugees or asylum seekers hosted in Turkey. Design, Setting, and Participants: This economic evaluation was performed as a prespecified part of an assessor-blinded randomized clinical trial conducted between October 1, 2018, and November 30, 2019, with 6-month follow-up. A total of 627 adults with psychological distress but no diagnosed psychiatric disorder were randomly assigned to the intervention group or the enhanced usual care group. Interventions: The SH+ program was a 5-session (2 hours each), group-based, stress management course in which participants learned self-help skills for managing stress by listening to audio sessions. The SH+ sessions were facilitated by briefly trained, nonspecialist individuals, and an illustrated book was provided to group members. Th intervention group received the SH+ intervention plus enhanced usual care; the control group received only enhanced usual care from the local health care system. Enhanced usual care included access to free health care services provided by primary and secondary institutions plus details on nongovernmental organizations and freely available mental health services, social services, and community networks for people under temporary protection of Turkey and refugees. Main Outcomes and Measures: The primary outcome measure was incremental cost per quality-adjusted life-year (QALY) gained from the perspective of the Turkish health care system. An intention-to-treat analysis was used including all participants who were randomized and for whom baseline data on costs and QALYs were available. Data were analyzed September 30, 2020, to July 30

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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.

BACKGROUND: Little is known about changes of mental health during the COVID-19 pandemic in potentially disadvantaged groups. We investigated changes in anxiety and depression symptoms during the first year of the pandemic in six European countries and Australia by prior mental disorders and migration status. METHODS: Overall, 4674 adults answered a web-based survey in May-June 2020 and were followed by three repeated surveys up to February 2021. Information on psychosocial, financial and demographic, living conditions, prior mental disorders, depression and anxiety symptoms during the pandemic and migration status was collected. Weighted general estimation equations modelling was used to investigate the association between prior mental disorders, migration status, and symptoms over time. RESULTS: Most participants were <40 years old (48%), women (78%) and highly educated (62%). The baseline prevalence of depressive and anxiety symptoms ranged between 19%-45% and 13%-35%, respectively. In most countries, prevalence rates remained unchanged throughout the pandemic and were higher among people with prior mental disorders than without even after adjustment for several factors. We observed interactions between previous mental disorders and symptoms of anxiety or depression over time in two countries. No difference by migration status was noted. LIMITATIONS: Convenience sampling limits generalizability. Self-assessed symptoms of depression and anxiety might involve some misclassification. CONCLUSIONS: Depression and anxiety symptoms were worse among individuals with prior mental disorders than without, but there was no clear trend of worsening mental health in the observed groups during the observed period.

BACKGROUND AND AIMS: The coronavirus disease 2019 pandemic has challenged health services worldwide, with a worsening of healthcare workers' mental health within initial pandemic hotspots. In early 2022, the Omicron variant is spreading rapidly around the world. This study explores the effectiveness and cost-effectiveness of a stepped-care programme of scalable, internet-based psychological interventions for distressed health workers on self-reported anxiety and depression symptoms. METHODS: We present the study protocol for a multicentre (two sites), parallel-group (1:1 allocation ratio), analyst-blinded, superiority, randomised controlled trial. Healthcare workers with psychological distress will be allocated either to care as usual only or to care as usual plus a stepped-care programme that includes two scalable psychological interventions developed by the World Health Organization: A guided self-help stress management guide (Doing What Matters in Times of Stress) and a five-session cognitive behavioural intervention (Problem Management Plus). All participants will receive a single-session emotional support intervention, namely psychological first aid. We will include 212 participants. An intention-to-treat analysis using linear mixed models will be conducted to explore the programme's effect on anxiety and depression symptoms, as measured by the Patient Health Questionnaire - Anxiety and Depression Scale summary score at 21 weeks from baseline. Secondary outcomes include post-traumatic stress disorder symptoms, resilience, quality of life, cost impact and cost-effectiveness. CONCLUSIONS: This study is the first randomised trial that combines two World Health Organization psychological interventions tailored for health workers into one stepped-care programme. Results will inform occupational and mental health prevention, treatment, and recovery strategies. REGISTRATION DETAILS: ClinicalTrials.gov Identifier: NCT04980326.

Background: Longitudinal studies examining mental health trajectories in refugees and asylum seekers are scarce. Objectives: To investigate trajectories of psychological symptoms and wellbeing in refugees and asylum seekers, and identify factors associated with these trajectories. Method: 912 asylum seekers and refugees from the control arm of three trials in Europe (n = 229), Turkey (n = 320), and Uganda (n = 363) were included. We described trajectories of psychological symptoms and wellbeing, and used trauma exposure, age, marital status, education, and individual trial as predictors. Then, we assessed the bidirectional interactions between wellbeing and psychological symptoms, and the effect of each predictor on each outcome controlling for baseline values. Results: Symptom improvement was identified in all trials, and for wellbeing in 64.7% of participants in Europe and Turkey, versus 31.5% in Uganda. In Europe and Turkey domestic violence predicted increased symptoms at post-intervention (ß = 1.36, 95% CI 0.17-2.56), whilst murder of family members at 6-month follow-up (ß = 1.23, 95% CI 0.27-2.19). Lower wellbeing was predicted by murder of family member (ß = -1.69, 95% CI -3.06 to -0.32), having been kidnapped (ß = -1.67, 95% CI -3.19 to -0.15), close to death (ß = -1.38, 95% CI -2.70 to -0.06), and being in the host country ≥2 years (ß = -1.60, 95% CI -3.05 to -0.14). In Uganda at post-intervention, having been kidnapped predicted increased symptoms (ß = 2.11, 95% CI 0.58-3.65), and lack of shelter (ß = -2.51, 95% CI -4.44 to -0.58) and domestic violence predicted lower wellbeing (ß = -1.36, 95% CI -2.67 to -0.05). Conclusion: Many participants adapt to adversity, but contextual factors play a critical role in determining mental health trajectories.

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Mental disorders are one of the largest contributors to the burden of disease globally, this holds also for children and adolescents, especially in low-and middle-income countries. The prevalence and severity of these disorders are influenced by social determinants, including exposure to adversity. When occurring early in life, these latter events are referred to as adverse childhood experiences (ACEs). In this editorial, we provide an overview of the literature on the role of ACEs as social determinants of mental health through the lenses of global mental health. While the relation between ACEs and mental health has been extensively explored, most research was centred in higher income contexts. We argue that findings from the realm of global mental health should be integrated into that of ACEs, e.g. through preventative and responsive psychosocial interventions for children, adolescents and their caregivers. The field of global mental health should also undertake active efforts to better address ACEs in its initiatives, all with the goal of reducing the burden of mental disorders among children and adolescents globally., NA

Refugees are at high risk of developing mental disorders. There is no evidence from randomized controlled trials (RCTs) that psychological interventions can prevent the onset of mental disorders in this group. We assessed the effectiveness of a self-help psychological intervention developed by the World Health Organization, called Self-Help Plus, in preventing the development of mental disorders among Syrian refugees experiencing psychological distress in Turkey. A two-arm, assessor-masked RCT was conducted in two Turkish areas. Eligible participants were adult Syrian refugees experiencing psychological distress (General Health Questionnaire ≥3), but without a diagnosis of mental disorder. They were randomly assigned either to the Self-Help Plus arm (consisting of Self-Help Plus combined with Enhanced Care as Usual, ECAU) or to ECAU only in a 1:1 ratio. Self-Help Plus was delivered in a group format by two facilitators over five sessions. The primary outcome measure was the presence of any mental disorder assessed by the Mini International Neuropsychiatric Interview at six-month follow-up. Secondary outcome measures were the presence of mental disorders at post-intervention, and psychological distress, symptoms of post-traumatic stress disorder and depression, personally identified psychological outcomes, functional impairment, subjective well-being, and quality of life at post-intervention and six-month follow-up. Between October 1, 2018 and November 30, 2019, 1,186 refugees were assessed for inclusion. Five hundred forty-four people were ineligible, and 642 participants were enrolled and randomly assigned to either Self-Help Plus (N=322) or ECAU (N=320). Self-Help Plus participants were significantly less likely to have any mental disorders at six-month follow-up compared to the ECAU group (21.69% vs. 40.73%; Cramer's V = 0.205, p<0.001, risk ratio: 0.533, 95% CI: 0.408-0.696). Analysis of secondary outcomes suggested that Self-Help Plus was not effective immediat

Background: little is known about changes of mental health during the COVID-19 pandemic in potentially disadvantaged groups. We investigated changes in anxiety and depression symptoms during the first year of the pandemic in six European countries and Australia by prior mental disorders and migration status. Methods: overall, 4674 adults answered a web-based survey in May-June 2020 and were followed by three repeated surveys up to February 2021. Information on psychosocial, financial and demographic, living conditions, prior mental disorders, depression and anxiety symptoms during the pandemic and migration status was collected. Weighted general estimation equations modelling was used to investigate the association between prior mental disorders, migration status, and symptoms over time. Results: most participants were <40 years old (48%), women (78%) and highly educated (62%). The baseline prevalence of depressive and anxiety symptoms ranged between 19%-45% and 13%-35%, respectively. In most countries, prevalence rates remained unchanged throughout the pandemic and were higher among people with prior mental disorders than without even after adjustment for several factors. We observed interactions between previous mental disorders and symptoms of anxiety or depression over time in two countries. No difference by migration status was noted. Limitations: convenience sampling limits generalizability. Self-assessed symptoms of depression and anxiety might involve some misclassification. Conclusions: depression and anxiety symptoms were worse among individuals with prior mental disorders than without, but there was no clear trend of worsening mental health in the observed groups during the observed period., European Union (EU); Horizon 2020; Research and Innovation Programme Societal Challenges

Importance: the cost-effectiveness of the Self-Help Plus (SH+) program, a group-based, guided, self-help psychological intervention developed by the World Health Organization for people affected by adversity, is unclear. Objective: to investigate the cost-utility of providing the SH+ intervention combined with enhanced usual care vs enhanced usual care alone for Syrian refugees or asylum seekers hosted in Turkey. Design, setting, and participants: this economic evaluation was performed as a prespecified part of an assessor-blinded randomized clinical trial conducted between October 1, 2018, and November 30, 2019, with 6-month follow-up. A total of 627 adults with psychological distress but no diagnosed psychiatric disorder were randomly assigned to the intervention group or the enhanced usual care group. Interventions: the SH+ program was a 5-session (2 hours each), group-based, stress management course in which participants learned self-help skills for managing stress by listening to audio sessions. The SH+ sessions were facilitated by briefly trained, nonspecialist individuals, and an illustrated book was provided to group members. Th intervention group received the SH+ intervention plus enhanced usual care; the control group received only enhanced usual care from the local health care system. Enhanced usual care included access to free health care services provided by primary and secondary institutions plus details on nongovernmental organizations and freely available mental health services, social services, and community networks for people under temporary protection of Turkey and refugees. Main outcomes and measures: the primary outcome measure was incremental cost per quality-adjusted life-year (QALY) gained from the perspective of the Turkish health care system. An intention-to-treat analysis was used including all participants who were randomized and for whom baseline data on costs and QALYs were available. Data were analyzed September 30, 2020, to July 30, European Union (EU); Horizon 2020

Refugees are at high risk of developing mental disorders. There is no evidence from randomized controlled trials (RCTs) that psychological interventions can prevent the onset of mental disorders in this group. We assessed the effectiveness of a self-help psychological intervention developed by the World Health Organization, called Self-Help Plus, in preventing the development of mental disorders among Syrian refugees experiencing psychological distress in Turkey. A two-arm, assessor-masked RCT was conducted in two Turkish areas. Eligible participants were adult Syrian refugees experiencing psychological distress (General Health Questionnaire ?3), but without a diagnosis of mental disorder. They were randomly assigned either to the Self-Help Plus arm (consisting of Self-Help Plus combined with Enhanced Care as Usual, ECAU) or to ECAU only in a 1:1 ratio. Self-Help Plus was delivered in a group format by two facilitators over five sessions. The primary outcome measure was the presence of any mental disorder assessed by the Mini International Neuropsychiatric Interview at six-month follow-up. Secondary outcome measures were the presence of mental disorders at post-intervention, and psychological distress, symptoms of post-traumatic stress disorder and depression, personally identified psychological outcomes, functional impairment, subjective well-being, and quality of life at post-intervention and six-month follow-up. Between October 1, 2018 and November 30, 2019, 1,186 refugees were assessed for inclusion. Five hundred forty-four people were ineligible, and 642 participants were enrolled and randomly assigned to either Self-Help Plus (N=322) or ECAU (N=320). Self-Help Plus participants were significantly less likely to have any mental disorders at six-month follow-up compared to the ECAU group (21.69% vs. 40.73%; Cramer's V = 0.205, p<0.001, risk ratio: 0.533, 95% CI: 0.408-0.696). Analysis of secondary outcomes suggested that Self-Help Plus was not effective immediat, European Commission

Aims: as refugees and asylum seekers are at high risk of developing mental disorders, we assessed the effectiveness of Self-Help Plus (SH + ), a psychological intervention developed by the World Health Organization, in reducing the risk of developing any mental disorders at 12-month follow-up in refugees and asylum seekers resettled in Western Europe. Methods: refugees and asylum seekers with psychological distress (General Health Questionnaire-12 > 3) but without a mental disorder according to the Mini International Neuropsychiatric Interview (M.I.N.I.) were randomised to either SH + or enhanced treatment as usual (ETAU). The frequency of mental disorders at 12 months was measured with the M.I.N.I., while secondary outcomes included self-identified problems, psychological symptoms and other outcomes. Results: of 459 participants randomly assigned to SH + or ETAU, 246 accepted to be interviewed at 12 months. No difference in the frequency of any mental disorders was found (relative risk [RR] = 0.841; 95% confidence interval [CI] 0.389-1.819; p-value = 0.659). In the per protocol (PP) population, that is in participants attending at least three group-based sessions, SH + almost halved the frequency of mental disorders at 12 months compared to ETAU, however so few participants and events contributed to this analysis that it yielded a non-significant result (RR = 0.528; 95% CI 0.180-1.544; p-value = 0.230). SH + was associated with improvements at 12 months in psychological distress (p-value = 0.004), depressive symptoms (p-value = 0.011) and wellbeing (p-value = 0.001). Conclusions: the present study failed to show any long-term preventative effect of SH + in refugees and asylum seekers resettled in Western European countries. Analysis of the PP population and of secondary outcomes provided signals of a potential effect of SH + in the long-term, which would suggest the value of exploring the effects of booster sessions and strategies to increase SH + adherence., European Union (EU); Horizon 2020; European Commission; RE-DEFINE: Refugee Emergency: DEFining and Implementing Novel Evidence-based Psychosocial Interventions