Transforming mental health systems globally: principles and policy recommendations.

A burgeoning mental health crisis is emerging globally, regardless of each country's human resources or spending. We argue that effectively responding to this crisis is impeded by the dominant framing of mental ill health through the prism of diagnostic categories, leading to an excessive reliance on interventions that are delivered by specialists; a scarcity of widespread promotive, preventive, and recovery-oriented strategies; and failure to leverage diverse resources within communities. Drawing upon a series of syntheses, we identify five principles to transform current practices; namely, address harmful social environments across the life course, particularly in the early years; ensure that care is not contingent on a categorical diagnosis but aligned with the staging model of mental illness; empower diverse front-line providers to deliver psychosocial interventions; embrace a rights-based approach that seeks to provide alternatives to violence and coercion in care; and centre people with lived experience in all aspects of care. We recommend four policy actions which can transform these principles into reality: a whole of society approach to prevention and care; a redesign of the architecture of care delivery to provide a seamless continuum of care, tailored to the severity of the mental health condition; investing more in what works to enhance the impact and value of the investments; and ensuring accountability through monitoring and acting upon a set of mental health indicators. All these actions are achievable, relying-for the most part-on resources already available to every community and country. What they do require is the acceptance that business as usual will fail and the solutions to transforming mental health-care systems are already present within existing resources.

Reimagining the journey to recovery: The COVID-19 pandemic and global mental health.

In this editorial, guest editors Vikram Patel, Daisy Fancourt, Lola Kola, and Toshi Furukawa discuss the contents of the special issue on the pandemic and global mental health, highlighting key themes and providing important context.

Depression in young people.

Depression rates in young people have risen sharply in the past decade, especially in females, which is of concern because adolescence is a period of rapid social, emotional, and cognitive development and key life transitions. Adverse outcomes associated with depression in young people include depression recurrence; the onset of other psychiatric disorders; and wider, protracted impairments in interpersonal, social, educational, and occupational functioning. Thus, prevention and early intervention for depression in young people are priorities. Preventive and early intervention strategies typically target predisposing factors, antecedents, and symptoms of depression. Young people who have a family history of depression, exposure to social stressors (eg, bullying, discordant relationships, or stressful life events), and belong to certain subgroups (eg, having a chronic physical health problem or being a sexual minority) are at especially high risk of depression. Clinical antecedents include depressive symptoms, anxiety, and irritability. Evidence favours indicated prevention and targeted prevention to universal prevention. Emerging school-based and community-based social interventions show some promise. Depression is highly heterogeneous; therefore, a stepwise treatment approach is recommended, starting with brief psychosocial interventions, then a specific psychological therapy, and then an antidepressant medication.

Understanding the effects of a complex psychological intervention on symptoms of depression in Goa, India: findings from a causal mediation analysis.

BACKGROUND: Understanding how and under what circumstances a highly effective psychological intervention, improved symptoms of depression is important to maximise its clinical effectiveness. AIMS: To address this complexity, we estimate the indirect effects of potentially important mediators to improve symptoms of depression (measured with the Patient Health Questionnaire (PHQ-9)) in the Healthy Activity Program trial. METHOD: Interventional in(direct) effects were used to decompose the total effect of the intervention on PHQ-9 scores into the direct and indirect effects. The following indirect effects were considered: characteristics of sessions, represented by the number of sessions and homework completed; behavioural activation, according to an adapted version of the Behavioural Activation for Depression Scale - Short Form; and extra sessions offered to participants who did not respond to the intervention. RESULTS: Of the total effect of the intervention measured through the difference in PHQ-9 scores between treatment arms (mean difference: -2.1, bias-corrected 95% CI -3.2 to -1.5), 34% was mediated through improved levels of behavioural activation (mean difference: -0.7, bias-corrected 95% CI -1.2 to -0.4). There was no evidence to support the mediating role of characteristics of the sessions nor the extra sessions offered to participants who did not respond to the treatment. CONCLUSIONS: Findings from our robust mediation analyses confirmed the importance of targeting behavioural activation. Contrary to published literature, our findings suggest that neither the number of sessions nor proportion of homework completed improved outcomes. Moreover, in this context, alternative treatments other than extra sessions should be considered for patients who do not respond to the intervention.

A systematic review and meta-analysis on prevalence of and risk factors associated with depression, anxiety and insomnia in infectious diseases, including COVID-19: a call to action.

Infectious disease epidemics have become more frequent and more complex during the 21st century, posing a health threat to the general public and leading to psychological symptoms. The current study was designed to investigate the prevalence of and risk factors associated with depression, anxiety and insomnia symptoms during epidemic outbreaks, including COVID-19. We systematically searched the PubMed, Embase, Web of Science, OVID, Medline, Cochrane databases, bioRxiv and medRxiv to identify studies that reported the prevalence of depression, anxiety or insomnia during infectious disease epidemics, up to August 14th, 2020. Prevalence of mental symptoms among different populations including the general public, health workers, university students, older adults, infected patients, survivors of infection, and pregnant women across all types of epidemics was pooled. In addition, prevalence of mental symptoms during COVID-19 was estimated by time using meta-regression analysis. A total of 17,506 papers were initially retrieved, and a final of 283 studies met the inclusion criteria, representing a total of 948,882 individuals. The pooled prevalence of depression ranged from 23.1%, 95% confidential intervals (95% CI: [13.9-32.2]) in survivors to 43.3% (95% CI: [27.1-59.6]) in university students, the pooled prevalence of anxiety ranged from 25.0% (95% CI: [12.0-38.0]) in older adults to 43.3% (95% CI: [23.3-63.3]) in pregnant women, and insomnia symptoms ranged from 29.7% (95% CI: [24.4-34.9]) in the general public to 58.4% (95% CI: [28.1-88.6]) in university students. Prevalence of moderate-to-severe mental symptoms was lower but had substantial variation across different populations. The prevalence of mental problems increased over time during the COVID-19 pandemic among the general public, health workers and university students, and decreased among infected patients. Factors associated with increased prevalence for all three mental health symptoms included female sex, and having physical disorders, psychiatric disorders, COVID infection, colleagues or family members infected, experience of frontline work, close contact with infected patients, high exposure risk, quarantine experience and high concern about epidemics. Frequent exercise and good social support were associated with lower risk for these three mental symptoms. In conclusion, mental symptoms are common during epidemics with substantial variation across populations. The population-specific psychological crisis management are needed to decrease the burden of psychological problem and improve the mental wellbeing during epidemic.

Physical and psychiatric comorbidities among patients with severe mental illness as seen in Uganda.

While psychiatric and physical comorbidities in severe mental illness (SMI) have been associated with increased mortality and poor clinical outcomes, problem has received little attention in low- and middle-income countries (LMICs). This study established the prevalence of psychiatric (schizophrenia, bipolar affective disorder, and recurrent major depressive disorder) and physical (HIV/AIDS, syphilis, hypertension and obesity) comorbidities and associated factors among 1201 out-patients with SMI (schizophrenia, depression and bipolar affective disorder) attending care at two hospitals in Uganda. Participants completed an assessment battery including structured, standardised and locally translated instruments. SMIs were established using the MINI International Neuropsychiatric Interview version 7.2. We used logistic regression to determine the association between physical and psychiatric comorbidities and potential risk factors. Bipolar affective disorder was the most prevalent (66.4%) psychiatric diagnoses followed by schizophrenia (26.6%) and recurrent major depressive disorder (7.0%). Prevalence of psychiatric comorbidity was 9.1%, while physical disorder comorbidity was 42.6%. Specific comorbid physical disorders were hypertension (27.1%), obesity (13.8%), HIV/AIDS (8.2%) and syphilis (4.8%). Potentially modifiable factors independently significantly associated with psychiatric and physical comorbidities were: use of alcohol for both syphilis and hypertension comorbidities; and use of a mood stabilisers and khat in comorbidity with obesity. Only psychiatric comorbidity was positively associated with the negative outcomes of suicidality and risky sexual behaviour. The healthcare models for psychiatric care in LMICs such as Uganda should be optimised to address the high burden of psychiatric and physical comorbidities.

Protocol for an economic evaluation of scalable strategies to improve mental health among perinatal women: non-specialist care delivered via telemedicine vs. specialist care delivered in-person.

BACKGROUND: Perinatal depression affects an estimated 1 in 5 women in North America during the perinatal period, with annualized lifetime costs estimated at $20.6 billion CAD in Canada and over $45.9 billion USD in the US. Access to psychological treatments remains limited for most perinatal women suffering from depression and anxiety. Some barriers to effective care can be addressed through task-sharing to non-specialist providers and through telemedicine platforms. The cost-effectiveness of these strategies compared to traditional specialist and in-person models remains unknown. This protocol describes an economic evaluation of non-specialist providers and telemedicine, in comparison to specialist providers and in-person sessions within the ongoing Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT) trial. METHODS: The economic evaluation will be undertaken alongside the SUMMIT trial. SUMMIT is a pragmatic, randomized, non-inferiority trial across five North American study sites (N = 1,226) of the comparable effectiveness of two types of providers (specialist vs. non-specialist) and delivery modes (telemedicine vs. in-person) of a behavioural activation treatment for perinatal depressive and anxiety symptoms. The primary economic evaluation will be a cost-utility analysis. The outcome will be the incremental cost-effectiveness ratio, which will be expressed as the additional cost required to achieve an additional quality-adjusted life-year, as assessed by the EuroQol 5-Dimension 5-Level instrument. A secondary cost-effectiveness analysis will use participants' depressive symptom scores. A micro-costing analysis will be conducted to estimate the resources/costs required to implement and sustain the interventions; healthcare resource utilization will be captured via self-report. Data will be pooled and analysed using uniform price and utility weights to determine cost-utility across all trial sites. Secondary country-specific cost-utility and cost-effectiveness analyses will also be completed. Sensitivity analyses will be conducted, and cost-effectiveness acceptability-curves will be generated, in all instances. DISCUSSION: Results of this study are expected to inform key decisions related to dissemination and scale up of evidence-based psychological interventions in Canada, the US, and possibly worldwide. There is potential impact on real-world practice by informing decision makers of the long-term savings to the larger healthcare setting in services to support perinatal women with common mental health conditions.

The Impact of the COVID-19 Pandemic and Associated Control Measures on the Mental Health of the General Population : A Systematic Review and Dose-Response Meta-analysis.

BACKGROUND: To what extent the COVID-19 pandemic and its containment measures influenced mental health in the general population is still unclear. PURPOSE: To assess the trajectory of mental health symptoms during the first year of the pandemic and examine dose-response relations with characteristics of the pandemic and its containment. DATA SOURCES: Relevant articles were identified from the living evidence database of the COVID-19 Open Access Project, which indexes COVID-19-related publications from MEDLINE via PubMed, Embase via Ovid, and PsycInfo. Preprint publications were not considered. STUDY SELECTION: Longitudinal studies that reported data on the general population's mental health using validated scales and that were published before 31 March 2021 were eligible. DATA EXTRACTION: An international crowd of 109 trained reviewers screened references and extracted study characteristics, participant characteristics, and symptom scores at each timepoint. Data were also included for the following country-specific variables: days since the first case of SARS-CoV-2 infection, the stringency of governmental containment measures, and the cumulative numbers of cases and deaths. DATA SYNTHESIS: In a total of 43 studies (331 628 participants), changes in symptoms of psychological distress, sleep disturbances, and mental well-being varied substantially across studies. On average, depression and anxiety symptoms worsened in the first 2 months of the pandemic (standardized mean difference at 60 days, -0.39 [95% credible interval, -0.76 to -0.03]); thereafter, the trajectories were heterogeneous. There was a linear association of worsening depression and anxiety with increasing numbers of reported cases of SARS-CoV-2 infection and increasing stringency in governmental measures. Gender, age, country, deprivation, inequalities, risk of bias, and study design did not modify these associations. LIMITATIONS: The certainty of the evidence was low because of the high risk of bias in included studies and the large amount of heterogeneity. Stringency measures and surges in cases were strongly correlated and changed over time. The observed associations should not be interpreted as causal relationships. CONCLUSION: Although an initial increase in average symptoms of depression and anxiety and an association between higher numbers of reported cases and more stringent measures were found, changes in mental health symptoms varied substantially across studies after the first 2 months of the pandemic. This suggests that different populations responded differently to the psychological stress generated by the pandemic and its containment measures. PRIMARY FUNDING SOURCE: Swiss National Science Foundation. (PROSPERO: CRD42020180049).

Adaptation and translation of a scalable measure for assessing health worker competence to deliver a brief psychological intervention: A case study from central India of its comparison to a performance-based measure.

Efforts to reduce the global burden of common mental disorders have focused on scaling up evidence-based training programs for non-specialist providers to deliver brief psychological interventions. To evaluate these provider training programs, appropriate and scalable assessments of competency need to be developed alongside them. We followed a systematic approach for the cultural adaptation and translation into Hindi of a valid, English, multiple-choice applied knowledge measure to assess non-specialists' competence to deliver a brief psychological intervention for depression in rural India. We then explored the relationship between the performance of 30 non-specialist providers on the same written measure compared with a structured performance-based measure consisting of two role-plays. The results of the multiple-choice assessment had an overall mean score of 37.40 (SD = 11.31) compared to the mean scores of role-play A (the easier role-play) of 43.25 (SD = 14.50) and role-play B (the more difficult role-play) of 43.25 (SD = 13.00). Role-play performance-based measures and written applied knowledge measures represent different approaches with unique strengths and challenges to measuring competence. Scaling up training programs requires the development of scalable methods for competency assessment. Exploring the relationship between these two measures, our team found no apparent differences between the two modes of assessment. Continued comparison of these approaches is needed to determine the consistency of outcomes across the two formats and to link the scores on these measures with clinical performance as reflected by the quality of care and patient outcomes.Trial Registration: ClinicalTrials.gov Identifier: NCT04157816; 8th November 2019.

Relationship between the Bolsa Família national cash transfer programme and suicide incidence in Brazil: A quasi-experimental study.

BACKGROUND: Socioeconomic factors have been consistently associated with suicide, and economic recessions are linked to rising suicide rates. However, evidence on the impact of socioeconomic interventions to reduce suicide rates is limited. This study investigates the association of the world's largest conditional cash transfer programme with suicide rates in a cohort of half of the Brazilian population. METHODS AND FINDINGS: We used data from the 100 Million Brazilian Cohort, covering a 12-year period (2004 to 2015). It comprises socioeconomic and demographic information on 114,008,317 individuals, linked to the "Bolsa Família" programme (BFP) payroll database, and nationwide death registration data. BFP was implemented by the Brazilian government in 2004. We estimated the association of BFP using inverse probability of treatment weighting, estimating the weights for BFP beneficiaries (weight = 1) and nonbeneficiaries by the inverse probability of receiving treatment (weight = E(ps)/(1-E(ps))). We used an average treatment effect on the treated (ATT) estimator and fitted Poisson models to estimate the incidence rate ratios (IRRs) for suicide associated with BFP experience. At the cohort baseline, BFP beneficiaries were younger (median age 27.4 versus 35.4), had higher unemployment rates (56% versus 32%), a lower level of education, resided in rural areas, and experienced worse household conditions. There were 36,742 suicide cases among the 76,532,158 individuals aged 10 years, or older, followed for 489,500,000 person-years at risk. Suicide rates among beneficiaries and nonbeneficiaries were 5.4 (95% CI = 5.32, 5.47, p < 0.001) and 10.7 (95% CI = 10.51, 10.87, p < 0.001) per 100,000 individuals, respectively. BFP beneficiaries had a lower suicide rate than nonbeneficiaries (IRR = 0.44, 95% CI = 0.42, 0.45, p < 0.001). This association was stronger among women (IRR = 0.36, 95% CI = 0.33, 0.38, p < 0.001), and individuals aged between 25 and 59 (IRR = 0.41, 95% CI = 0.40, 0.43, p < 0.001). Study limitations include a lack of control for previous mental disorders and access to means of suicide, and the possible under-registration of suicide cases due to stigma. CONCLUSIONS: We observed that BFP was associated with lower suicide rates, with similar results in all sensitivity analyses. These findings should help to inform policymakers and health authorities to better design suicide prevention strategies. Targeting social determinants using cash transfer programmes could be important in limiting suicide, which is predicted to rise with the economic recession, consequent to the Coronavirus Disease 2019 (COVID-19) pandemic.

Development of a cost of illness inventory questionnaire for children with autism spectrum disorder in South Asia.

BACKGROUND: The economic burden of autism is substantial and includes a range of costs, including healthcare, education, productivity losses, informal care and respite care, among others. In India, approximately, 2 million children aged 2-9 years have autism. Given the likely substantial burden of illness and the need to identify effective and cost-effective interventions, this research aimed to produce a comprehensive cost of illness inventory (COII) suitable for children with autism in South Asia (India) to support future research. METHODS: A structured and iterative design process was followed to create the COII, including literature reviews, interviews with caregivers, pilot testing and translation. Across the development of the COII, thirty-two families were involved in the design and piloting of the tool. The COII was forward translated (from English to Hindi) and back translated. Each stage of the process of development of the COII resulted in the further refinement of the tool. RESULTS: Domains covered in the final COII include education, childcare, relocation, healthcare contacts (outpatient, inpatient, medical emergencies, investigations and medication), religious retreats and rituals, specialist equipment, workshops and training, special diet, support and care, certification, occupational adjustments and government rebates/schemes. Administration and completion of the COII determined it to be feasible to complete in 35 minutes by qualified and trained researchers. The final COII is hosted by REDCap Cloud and is a bilingual instrument (Hindi and English). CONCLUSIONS: The COII was developed using experiences gathered from an iterative process in a metropolitan area within the context of one low- and middle-income country (LMIC) setting, India. Compared to COII tools used for children with autism in high-income country settings, additional domains were required, such as complimentary medication (e.g. religious retreats and homeopathy). The COII will allow future research to quantify the cost of illness of autism in India from a broad perspective and will support relevant economic evaluations. Understanding the process of developing the questionnaire will help researchers working in LMICs needing to adapt the current COII or developing similar questionnaires.

Effect of Paroxetine or Quetiapine Combined With Oxycodone vs Oxycodone Alone on Ventilation During Hypercapnia: A Randomized Clinical Trial.

Importance: Opioids can cause severe respiratory depression by suppressing feedback mechanisms that increase ventilation in response to hypercapnia. Following the addition of boxed warnings to benzodiazepine and opioid products about increased respiratory depression risk with simultaneous use, the US Food and Drug Administration evaluated whether other drugs that might be used in place of benzodiazepines may cause similar effects. Objective: To study whether combining paroxetine or quetiapine with oxycodone, compared with oxycodone alone, decreases the ventilatory response to hypercapnia. Design, Setting, and Participants: Randomized, double-blind, crossover clinical trial at a clinical pharmacology unit (West Bend, Wisconsin) with 25 healthy participants from January 2021 through May 25, 2021. Interventions: Oxycodone 10 mg on days 1 and 5 and the following in a randomized order for 5 days: paroxetine 40 mg daily, quetiapine twice daily (increasing daily doses from 100 mg to 400 mg), or placebo. Main Outcomes and Measures: Ventilation at end-tidal carbon dioxide of 55 mm Hg (hypercapnic ventilation) using rebreathing methodology assessed for paroxetine or quetiapine with oxycodone, compared with placebo and oxycodone, on days 1 and 5 (primary) and for paroxetine or quetiapine alone compared with placebo on day 4 (secondary). Results: Among 25 participants (median age, 35 years [IQR, 30-40 years]; 11 female [44%]), 19 (76%) completed the trial. The mean hypercapnic ventilation was significantly decreased with paroxetine plus oxycodone vs placebo plus oxycodone on day 1 (29.2 vs 34.1 L/min; mean difference [MD], -4.9 L/min [1-sided 97.5% CI, -∞ to -0.6]; P = .01) and day 5 (25.1 vs 35.3 L/min; MD, -10.2 L/min [1-sided 97.5% CI, -∞ to -6.3]; P < .001) but was not significantly decreased with quetiapine plus oxycodone vs placebo plus oxycodone on day 1 (33.0 vs 34.1 L/min; MD, -1.2 L/min [1-sided 97.5% CI, -∞ to 2.8]; P = .28) or on day 5 (34.7 vs 35.3 L/min; MD, -0.6 L/min [1-sided 97.5% CI, -∞ to 3.2]; P = .37). As a secondary outcome, mean hypercapnic ventilation was significantly decreased on day 4 with paroxetine alone vs placebo (32.4 vs 41.7 L/min; MD, -9.3 L/min [1-sided 97.5% CI, -∞ to -3.9]; P < .001), but not with quetiapine alone vs placebo (42.8 vs 41.7 L/min; MD, 1.1 L/min [1-sided 97.5% CI, -∞ to 6.4]; P = .67). No drug-related serious adverse events were reported. Conclusions and Relevance: In this preliminary study involving healthy participants, paroxetine combined with oxycodone, compared with oxycodone alone, significantly decreased the ventilatory response to hypercapnia on days 1 and 5, whereas quetiapine combined with oxycodone did not cause such an effect. Additional investigation is needed to characterize the effects after longer-term treatment and to determine the clinical relevance of these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT04310579.

Scaling Up Parenting Interventions is Critical for Attaining the Sustainable Development Goals.

Of all the potentially modifiable influences affecting children's development and mental health across the life course, none is more important than the quality of parenting and family life. In this position paper, we argue that parenting is fundamentally linked to the development of life skills that children need in order to achieve the United Nations Sustainable Development Goals. We discuss key principles that should inform the development of a global research and implementation agenda related to scaling up evidence-based parenting support programs. Research over the past 50 years has shown that parenting support programs of varied intensity and delivery modality can improve a wide range of developmental, emotional, behavioral and health outcomes for parents and their children. Such findings have been replicated across culturally and socioeconomically diverse samples, albeit primarily in studies from Western countries. We highlight the evidence for the relevance of parenting interventions for attaining the SDGs globally, and identify the barriers to and strategies for achieving their scale-up. The implications of the global COVID-19 pandemic for the delivery of evidence-based parenting support are also discussed.

Associations of parental depression during adolescence with cognitive development in later life in China: A population-based cohort study.

BACKGROUND: Prior research has underscored negative impacts of perinatal parental depression on offspring cognitive performance in early childhood. However, little is known about the effects of parental depression during adolescence on offspring cognitive development. METHODS AND FINDINGS: This study used longitudinal data from the nationally representative China Family Panel Studies (CFPS). The sample included 2,281 adolescents aged 10-15 years (the median age was 13 years with an interquartile range between 11 and 14 years) in 2012 when their parents were surveyed for depression symptoms with the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). The sample was approximately balanced by sex, with 1,088 females (47.7%). We examined the associations of parental depression in 2012 with offspring cognitive performance (measured by mathematics, vocabulary, immediate word recall, delayed word recall, and number series tests) in subsequent years (i.e., 2014, 2016, and 2018) using linear regression models, adjusting for various offspring (i.e., age, sex, and birth order), parent (i.e., parents' education level, age, whether living with the offspring, and employment status), and household characteristics (i.e., place of residence, household income, and the number of offspring). We found parental depression during adolescence to be significantly associated with worse cognitive performance in subsequent years, in both crude and adjusted models. For example, in the crude models, adolescents whose mothers had depression symptoms in 2012 scored 1.0 point lower (95% confidence interval [CI]: -1.2 to -0.8, p < 0.001) in mathematics in 2014 compared to those whose mothers did not have depression symptoms; after covariate adjustment, this difference marginally reduced to 0.8 points (95% CI: -1.0 to -0.5, p < 0.001); the associations remained robust after further adjusting for offspring earlier cognitive ability in toddlerhood (-1.2, 95% CI: -1.6, -0.9, p < 0.001), offspring cognitive ability in 2012 (-0.6, 95% CI: -0.8, -0.3, p < 0.001), offspring depression status (-0.7, 95% CI: -1.0, -0.5, p < 0.001), and parents' cognitive ability (-0.8, 95% CI: -1.2, -0.3, p < 0.001). In line with the neuroplasticity theory, we observed stronger associations between maternal depression and mathematical/vocabulary scores among the younger adolescents (i.e., 10-11 years) than the older ones (i.e., 12-15 years). For example, the association between maternal depression and 2014 vocabulary scores was estimated to be -2.1 (95% CI: -2.6, -1.6, p < 0.001) in those aged 10-11 years, compared to -1.2 (95% CI: -1.6, -0.8, p < 0.001) in those aged 12-15 years with a difference of 0.9 (95% CI: 0.2, 1.6, p = 0.010). We also observed a stronger association of greater depression severity with worse mathematical scores. The primary limitations of this study were the relatively high attrition rate and residual confounding. CONCLUSIONS: In this study, we observed that parental depression during adolescence was associated with adverse offspring cognitive development assessed up to 6 years later. These findings highlight the intergenerational association between depression in parents and cognitive development across the early life course into adolescence.

Effectiveness and costs associated with a lay counselor-delivered, brief problem-solving mental health intervention for adolescents in urban, low-income schools in India: 12-month outcomes of a randomized controlled trial.

BACKGROUND: Psychosocial interventions for adolescent mental health problems are effective, but evidence on their longer-term outcomes is scarce, especially in low-resource settings. We report on the 12-month sustained effectiveness and costs of scaling up a lay counselor-delivered, transdiagnostic problem-solving intervention for common adolescent mental health problems in low-income schools in New Delhi, India. METHODS AND FINDINGS: Participants in the original trial were 250 school-going adolescents (mean [M] age = 15.61 years, standard deviation [SD] = 1.68), including 174 (69.6%) who identified as male. Participants were recruited from 6 government schools over a period of 4 months (August 20 to December 14, 2018) and were selected on the basis of elevated mental health symptoms and distress/functional impairment. A 2-arm, randomized controlled trial design was used to examine the effectiveness of a lay counselor-delivered, problem-solving intervention (4 to 5 sessions over 3 weeks) with supporting printed booklets (intervention arm) in comparison with problem solving delivered via printed booklets alone (control arm), at the original endpoints of 6 and 12 weeks. The protocol was modified, as per the recommendation of the Trial Steering Committee, to include a post hoc extension of the follow-up period to 12 months. Primary outcomes were adolescent-reported psychosocial problems (Youth Top Problems [YTP]) and mental health symptoms (Strengths and Difficulties Questionnaire [SDQ] Total Difficulties scale). Other self-reported outcomes included SDQ subscales, perceived stress, well-being, and remission. The sustained effects of the intervention were estimated at the 12-month endpoint and over 12 months (the latter assumed a constant effect across 3 follow-up points) using a linear mixed model for repeated measures and involving complete case analysis. Sensitivity analyses examined the effect of missing data using multiple imputations. Costs were estimated for delivering the intervention during the trial and from modeling a scale-up scenario, using a retrospective ingredients approach. Out of the 250 original trial participants, 176 (70.4%) adolescents participated in the 12-month follow-up assessment. One adverse event was identified during follow-up and deemed unrelated to the intervention. Evidence was found for intervention effects on both SDQ Total Difficulties and YTP at 12 months (YTP: adjusted mean difference [AMD] = -0.75, 95% confidence interval [CI] = -1.47, -0.03, p = 0.04; SDQ Total Difficulties: AMD = -1.73, 95% CI = -3.47, 0.02, p = 0.05), with stronger effects over 12 months (YTP: AMD = -0.98, 95% CI = -1.51, -0.45, p < 0.001; SDQ Total Difficulties: AMD = -1.23, 95% CI = -2.37, -0.09; p = 0.03). There was also evidence for intervention effects on internalizing symptoms, impairment, perceived stress, and well-being over 12 months. The intervention effect was stable for most outcomes on sensitivity analyses adjusting for missing data; however, for SDQ Total Difficulties and impairment, the effect was slightly attenuated. The per-student cost of delivering the intervention during the trial was $3 United States dollars (USD; or $158 USD per case) and for scaling up the intervention in the modeled scenario was $4 USD (or $23 USD per case). The scaling up cost accounted for 0.4% of the per-student school budget in New Delhi. The main limitations of the study's methodology were the lack of sample size calculations powered for 12-month follow-up and the absence of cost-effectiveness analyses using the primary outcomes. CONCLUSIONS: In this study, we observed that a lay counselor-delivered, brief transdiagnostic problem-solving intervention had sustained effects on psychosocial problems and mental health symptoms over the 12-month follow-up period. Scaling up this resource-efficient intervention is an affordable policy goal for improving adolescents' access to mental health care in low-resource settings. The findings need to be interpreted with caution, as this study was a post hoc extension, and thus, the sample size calculations did not take into account the relatively high attrition rate observed during the long-term follow-up. TRIAL REGISTRATION: ClinicalTrials.gov NCT03630471.

Multiple mediation analysis of the peer-delivered Thinking Healthy Programme for perinatal depression: findings from two parallel, randomised controlled trials.

BACKGROUND: Low-intensity psychosocial interventions have been effective in targeting perinatal depression, but relevant mechanisms of change remain unknown. AIMS: To examine three theoretically informed mediators of the Thinking Healthy Programme Peer-delivered (THPP), an evidence-based psychosocial intervention for perinatal depression, on symptom severity in two parallel, randomised controlled trials in Goa, India and Rawalpindi, Pakistan. METHOD: Participants included pregnant women aged ≥18 years with moderate to severe depression, as defined by a Patient Health Questionnaire 9 (PHQ-9) score ≥10, and were randomised to either THPP or enhanced usual care. We examine whether three prespecified variables (patient activation, social support and mother-child attachment) at 3 months post-childbirth mediated the effects of THPP interventions of perinatal depressive symptom severity (PHQ-9) at the primary end-point of 6 months post-childbirth. We first examined individual mediation within each trial (n = 280 in India and n = 570 in Pakistan), followed by a pooled analysis across both trials (N = 850). RESULTS: In both site-specific and pooled analyses, patient activation and support at 3 months independently mediated the intervention effects on depressive symptom severity at 6 months, accounting for 23.6 and 18.2% of the total effect of THPP, respectively. The intervention had no effect on mother-child attachment scores, thus there was no evidence that this factor mediated the intervention effect. CONCLUSIONS: The effects of the psychosocial intervention on depression outcomes in mothers were mediated by the same two factors in both contexts, suggesting that such interventions seeking to alleviate perinatal depression should target both social support and patient activation levels. DECLARATION OF INTEREST: None.

Annual Research Review: Achieving universal health coverage for young children with autism spectrum disorder in low- and middle-income countries: a review of reviews.

BACKGROUND: Autism presents with similar prevalence and core impairments in diverse populations. We conducted a scoping review of reviews to determine key barriers and innovative strategies which can contribute to attaining universal health coverage (UHC), from early detection to effective interventions for autism in low- and middle-income countries (LAMIC). METHODS: A systematic literature search of review articles was conducted. Reviews relevant to the study research question were included if they incorporated papers from LAMIC and focused on children (

Psychosocial interventions for self-harm in low-income and middle-income countries: systematic review and theory of change.

PURPOSE: To synthesise the evidence on effectiveness, acceptability and the delivery mechanisms of psychosocial interventions for self-harm in low and middle income countries and to develop a pathway of change specific for self-harm interventions. METHOD: Studies reporting one or more patient or implementation outcomes of a psychosocial intervention targeting self-harm and conducted in low- and middle-income countries were included. Taxonomy of treatment components and a theory of change map was created using information from the studies. RESULTS: We identified thirteen studies including nine randomised controlled trials (RCT), three non-RCTs, and a single experimental case design study. A single study using postcard contact and another using cognitive behaviour therapy (CBT) reported a reduction in self-harm attempts. Suicidal ideations were significantly reduced with CBT, volitional help sheets and postcard contact in different studies. Suicide risk assessment, problem solving and self-validation were the most frequently used elements in interventions. Goal-setting was the technique used most commonly. Cultural adaptations of psychotherapies were used in two studies. High attrition rates in psychotherapy trials, limited benefit of the delivery of treatment by non-specialist providers, and variable benefit observed using phone contact as a means to deliver intervention were other important findings. CONCLUSION: There were no strong positive findings to draw definitive conclusions. Limited availability and evidence for culturally adapted interventions in self-harm, lack of evaluation of task sharing using evidence based interventions as well as a dearth in evaluation and reporting of various intervention delivery models in low- and middle-income countries were major literature gaps.

Effect of Oral Ranitidine on Urinary Excretion of N-Nitrosodimethylamine (NDMA): A Randomized Clinical Trial.

Importance: In 2019, the US Food and Drug Administration (FDA) received a citizen petition indicating that ranitidine contained the probable human carcinogen N-nitrosodimethylamine (NDMA). In addition, the petitioner proposed that ranitidine could convert to NDMA in humans; however, this was primarily based on a small clinical study that detected an increase in urinary excretion of NDMA after oral ranitidine consumption. Objective: To evaluate the 24-hour urinary excretion of NDMA after oral administration of ranitidine compared with placebo. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled, crossover clinical trial at a clinical pharmacology unit (West Bend, Wisconsin) conducted in 18 healthy participants. The study began in June 2020, and the end of participant follow-up was July 1, 2020. Interventions: Participants were randomized to 1 of 4 treatment sequences and over 4 periods received ranitidine (300 mg) and placebo (randomized order) with a noncured-meats diet and then a cured-meats diet. The cured-meats diet was designed to have higher nitrites, nitrates (nitrate-reducing bacteria can convert nitrates to nitrites), and NDMA. Main Outcome and Measure: Twenty-four-hour urinary excretion of NDMA. Results: Among 18 randomized participants (median age, 33.0 [interquartile range {IQR}, 28.3 to 42.8] years; 9 women [50%]; 7 White [39%], 11 African American [61%]; and 3 Hispanic or Latino ethnicity [17%]), 17 (94%) completed the trial. The median 24-hour NDMA urinary excretion values for ranitidine and placebo were 0.6 ng (IQR, 0 to 29.7) and 10.5 ng (IQR, 0 to 17.8), respectively, with a noncured-meats diet and 11.9 ng (IQR, 5.6 to 48.6) and 23.4 ng (IQR, 8.6 to 36.7), respectively, with a cured-meats diet. There was no statistically significant difference between ranitidine and placebo in 24-hour urinary excretion of NDMA with a noncured-meats diet (median of the paired differences, 0 [IQR, -6.9 to 0] ng; P = .54) or a cured-meats diet (median of the paired differences, -1.1 [IQR, -9.1 to 11.5] ng; P = .71). No drug-related serious adverse events were reported. Conclusions and Relevance: In this trial that included 18 healthy participants, oral ranitidine (300 mg), compared with placebo, did not significantly increase 24-hour urinary excretion of NDMA when participants consumed noncured-meats or cured-meats diets. The findings do not support that ranitidine is converted to NDMA in a general, healthy population. Trial Registration: ClinicalTrials.gov Identifier: NCT04397445.

When the trial ends: moral experiences of caregiving in a randomized controlled trial in Goa, India.

This is an ethnographic study that examines the experiences of peer counsellors in the Thinking Healthy Programme Peer-delivered (THPP), a randomized controlled trial of a psychological intervention for perinatal depression in Goa, India. Based on nine months of fieldwork from 2015 to 2017 and through caregiving theories posited by one of us, we examine how caregiving is experienced by peer counsellors in a randomized controlled trial, a context in which care is given for a finite period and is removed at the study's end. Analysis of our data generated three themes: caregiving as a reciprocated process that impacts peer counsellor and participant; memories of care, with attention to the space that caregiving occupies in the memories and subjectivities of peer counsellors; and the end of the trial as experienced as a removal of care in the community of the counsellors. We posit that the moral aspects of caregiving are particularly important for peer counsellors, and that the context of randomized controlled trials is central to these moral experiences, particularly at the trial's end, when peer counsellors are asked to end care that, in many cases, remains expressed as needed.