Add-on Sodium Benzoate and N-Acetylcysteine in Patients With Early Schizophrenia Spectrum Disorder: A Multicenter, Double-Blind, Randomized Placebo-Controlled Feasibility Trial.

Background and Hypothesis: Oxidative stress pathways may play a role in schizophrenia through direct neuropathic actions, microglial activation, inflammation, and by interfering with NMDA neurotransmission. N-acetylcysteine (NAC) has been shown to improve negative symptoms of schizophrenia, however, results from trials of other compounds targeting NMDA neurotransmission have been mixed. This may reflect poor target engagement but also that risk mechanisms act in parallel. Sodium Benzoate (NaB) could have an additive with NAC to act on several pathophysiological mechanisms implicated in schizophrenia. Study Design: A multicenter, 12 weeks, 2 × 2 factorial design, randomized double-blind placebo-controlled feasibility trial of NaB and NAC added to standard treatment in 68 adults with early schizophrenia. Primary feasibility outcomes included recruitment, retention, and completion of assessments as well as acceptability of the study interventions. Psychosis symptoms, functioning, and cognitive assessments were also assessed. Study Results: We recruited our desired sample (n = 68) and retained 78% (n = 53) at 12 weeks, supporting the feasibility of recruitment and retention. There were no difficulties in completing clinical outcome schedules. Medications were well tolerated with no dropouts due to side effects. This study was not powered to detect clinical effect and as expected no main effects were found on the majority of clinical outcomes. Conclusions: We demonstrated feasibility of conducting a clinical trial of NaB and NAC. Given the preliminary nature of this study, we cannot draw firm conclusions about the clinical efficacy of either agent, and a large-scale trial is needed to examine if significant differences between treatment groups emerge. Trial Registration: ClinicalTrials.gov: NCT03510741.

Effectiveness of a group psychological intervention to reduce psychosocial distress in adolescents in Pakistan: a single-blind, cluster randomised controlled trial.

BACKGROUND: Emotional problems in adolescents living in low-income and middle-income countries (LMICs) remain largely unaddressed; key reasons include a scarcity of trained mental health professionals and unavailability of evidence-based, scalable psychological interventions. We aimed to evaluate the effectiveness of a non-specialist-delivered, group psychological intervention to reduce psychosocial distress in school-going adolescents in Pakistan. METHODS: In a two-arm, single-blind, cluster randomised controlled trial, eligible public school clusters from a rural subdistrict of Gujar Khan, Rawalpindi, Pakistan, were randomised (1:1, stratified by sex) using permuted block randomisation into intervention (n=20) and wait-list control (n=20) groups. Adolescents aged 13-15 years who provided informed assent and caregivers' consent were screened for psychosocial distress using the youth-reported Pediatric Symptoms Checklist (PSC; total psychosocial distress scores from 0 to 70), and those scoring 28 or more and their caregivers were enrolled into the trial. Adolescents in the intervention group received seven weekly group sessions and their caregivers received three biweekly group sessions in school settings from trained non-specialists. The primary outcome was change from baseline in the total PSC scores at 3 months post-intervention. The trial was registered prospectively with the International Standard Randomised Controlled Trial Number registry, ISRCTN17755448. FINDINGS: From the 40 school clusters that were included, 282 adolescents in the intervention group and 284 adolescents in the wait-list control group were enrolled between Nov 2 and Nov 30, 2021. At 3 months, adolescents in the intervention group had significantly lower mean total score on the PSC compared with adolescents in the control group (mean difference in change from baseline 3·48 [95% CI 1·66-5·29], p=0·0002, effect size 0·38 [95% CI 0·18-0·57]; adjusted mean difference 3·26 (95% CI 1·46-5·06], p=0·0004, effect size 0·35 (0·16-0·55). No adverse events were reported in either group. INTERPRETATION: The group psychological intervention most likely represents a feasible and effective option for adolescents with psychosocial distress in school settings. FUNDING: UK Medical Research Council, Foreign Commonwealth and Development Office, Department of Health and Social Care. TRANSLATION: For the Urdu translation of the abstract see Supplementary Materials section.

A randomised double-blind placebo-controlled trial of minocycline and/or omega-3 fatty acids added to treatment as usual for at risk Mental States: The NAYAB study.

BACKGROUND: Inflammatory mechanisms are thought to contribute to the onset of psychosis in persons with an at-risk mental state (ARMS). We investigated whether the anti-inflammatory properties of minocycline and omega-3 polyunsaturated fatty acids (omega-3), alone or synergistically, would prevent transition to psychosis in ARMS in a randomised, double-blind, placebo-controlled trial in Pakistan. METHODS: 10,173 help-seeking individuals aged 16-35 years were screened using the Prodromal Questionaire-16. Individuals scoring 6 and over were interviewed using the Comprehensive Assessment of At-Risk Mental States (CAARMS) to confirm ARMS. Participants (n = 326) were randomised to minocycline, omega-3, combined minocycline and omega-3 or to double placebo for 6 months. The primary outcome was transition to psychosis at 12 months. FINDINGS: Forty-five (13.8 %) participants transitioned to psychosis. The risk of transition was greater in those randomised to omega-3 alone or in combination with minocycline (17.3.%), compared to 10.4 % in those not exposed to omega-3; a risk-ratio (RR) of 1.67, 95 % CI [0.95, 2.92] p = 0.07. The RR for transitions on minocycline vs. no minocycline was 0.86, 95 % CI [0.50, 1.49] p > 0.10. In participants who did not become psychotic, CAARMS and depression symptom scores were reduced at six and twelve months (mean CAARMS difference = 1.43; 95 % CI [0.33, 1.76] p < 0.01 in those exposed to omega-3. Minocycline did not affect CAARMS or depression scores. INTERPRETATION: In keeping with other studies, omega-3 appears to have beneficial effects on ARMS and mood symptom severity but it increased transition to psychosis, which may reflect metabolic or developmental consequences of chronic poor nutrition in the population. Transition to psychosis was too rare to reveal a preventative effect of minocycline but minocycline did not improve symptom severity. ARMS symptom severity and transition to psychosis appear to have distinct pathogeneses which are differentially modulated by omega-3 supplementation. FUNDING: The study was funded by the Stanley Research Medical Institute.

Tobacco use in people with severe mental illness: Findings from a multi-country survey of mental health institutions in South Asia.

INTRODUCTION: People with severe mental illness (SMI) tend to die early due to cardiovascular and respiratory diseases, which may be linked to tobacco use. There is limited information on tobacco use in people with SMI in low- and middle-income countries where most tobacco users reside. We present novel data on tobacco use in people with SMI and their access to tobacco cessation advice in South Asia. METHODS: We conducted a multi-country survey of adults with SMI attending mental health facilities in Bangladesh, India, and Pakistan. Using data collected with a standardized WHO STEPS survey tool, we estimated the prevalence and distribution of tobacco use and assessed receipt of tobacco cessation advice. RESULTS: We recruited 3874 participants with SMI; 46.8% and 15.0% of men and women consumed tobacco, respectively. Smoking prevalence in men varied by country (Bangladesh 42.8%, India 20.1% and Pakistan 31.7%); <4% of women reported smoking in each country. Smokeless tobacco use in men also varied by country (Bangladesh 16.2%, India 18.2% and Pakistan 40.8%); for women, it was higher in Bangladesh (19.1%), but similar in India (9.9%) and Pakistan (9.1%). Just over a third of tobacco users (38.4%) had received advice to quit tobacco. Among smokers, 29.1% (n=244) made at least one quit attempt in the past year. There was strong evidence for the association between tobacco use and the severity of depression (OR=1.29; 95% CI: 1.12-1.48) and anxiety (OR=1.29; 95% CI: 1.12-1.49). CONCLUSIONS: As observed in high-income countries, we found higher tobacco use in people with SMI, particularly in men compared with rates reported for the general population in South Asia. Tobacco cessation support within mental health services offers an opportunity to close the gap in life expectancy between SMI and the general population. STUDY REGISTRATION: ISRCTN88485933; https://doi.org/10.1186/ISRCTN88485933 39.

Impact of severe mental illnesses on health-related quality of life among patients attending the Institute of Psychiatry, Rawalpindi from 2019 to 2021: A cross-sectional study.

BACKGROUND: Severe mental illnesses have huge impact on health-related quality of life. They contribute to significant morbidity in terms of number of number of years of life lost in form DALYS (disability adjusted life years) and shorter life expectancy and early mortality. There is limited evidence on their burden in low- and middle-income countries like Pakistan. OBJECTIVE: To determine the health-related quality of life in patients suffering from severe mental illness (schizophrenia, depression, and bipolar affective disorder) and demographic factors associated with poor health related quality of life in these patients. METHODOLOGY: This was descriptive cross sectional, using retrospective record view of data. Study was done under IMPACT (Improving Mental And Physical health Together) Program, which conducted a multi-morbidity survey conducted at institute of psychiatry, Benazir Bhutto hospital, Rawalpindi, using EQ 5d 5l (EURO QOL 5D5L) questionnaire having both subjective (EQVAS) and objective domains. RESULTS: The study included 922 SMI patients, of whom 555 participants (60.2%) were males and 367(39.69%) were females. The participants suffered from major depressive disorder (422;45.8%), followed by bipolar affective disorder (392; 42.51%) and schizophrenia (108;11.7%). Most participants were in a younger age group with (80%) of population being below 50 years old and had education level below secondary education (57.4%). In the analysis of association between EQ-VAS (subjective quality of life scale) and demographic factors, a significant association was found for marital status(p<0.001), gender (p< 0.001) and education (p< 0.001). Women had lower EQ-VAS scores (M = 49.43±SD = 27.72) as compared to males (M = 58.81±SD = 27.1) and individuals with lower educational status also had lower mean scores. Additionally, participants who were single, divorced or widowed also had lower mean EQVAS scores. When health related quality of life was analyzed across SMI, it was lower in all SMI, but was significantly lower for depression in both subjective and objective domains of health related of quality-of-life instrument. CONCLUSION: Health related quality of life is an important outcome measure and regular assessment of both subjective and objective aspects should be incorporated in management plans of patients suffering from severe mental illnesses.

Integrated Moving on After Breast Cancer and Culturally Adapted Cognitive Behavior Therapy intervention for depression and anxiety among Pakistani women with breast cancer: Protocol of a randomized controlled trial.

Objective: The diagnosis and treatment of breast cancer is associated with significant distress that has huge impact on survivors' quality of life. The objective of this study is to assess the effectiveness of an integrated intervention "Moving on After Breast Cancer (ABC) Plus culturally adapted Cognitive Behavior Therapy" (Moving on ABC Plus). Method: This is a randomized controlled trial that aims to recruit 354 breast cancer survivors from the inpatient and outpatient oncology departments in public and private hospitals in Karachi, Hyderabad, Lahore, Multan, and Rawalpindi in Pakistan. Patients scoring 10 or above on either the Patient Health Questionnaire-9 and/or the Generalized Anxiety Disorder scale (GAD-7) will be recruited. Baseline assessments will include Functional Assessment of Cancer Therapy-Breast; EuroQol-5D; Multidimensional Scale for Perceived Social Support; Intrusive Thoughts Scale; and Rosenberg Self-Esteem Scale. Participants randomized into intervention arm, Moving on ABC Plus, will receive 12 individual therapy sessions over 4 months. Follow-up will be completed at 4- and 6-month post-randomization, using all baseline instruments along with the Client Satisfaction Questionnaire (CSQ-8). We will also explore the participants', their family members', and the therapists' experiences of the trial and intervention. Results: We will be assessing the effectiveness of intervention in reducing depression and anxiety in breast cancer survivors as a primary outcome of the trial. The secondary outcomes will include effectiveness of intervention in terms of reduction in intrusive thoughts and improvement in health-related quality of life, self-esteem, and perceived social support. Conclusion: The results of the study will inform the design of a future larger randomized control trial with long-term follow-up.

A culturally adapted manual-assisted problem-solving intervention (CMAP) for adults with a history of self-harm: a multi-centre randomised controlled trial.

BACKGROUND: Self-harm is an important predictor of a suicide death. Culturally appropriate strategies for the prevention of self-harm and suicide are needed but the evidence is very limited from low- and middle-income countries (LMICs). This study aims to investigate the effectiveness of a culturally adapted manual-assisted problem-solving intervention (CMAP) for patients presenting after self-harm. METHODS: This was a rater-blind, multicenter randomised controlled trial. The study sites were all participating emergency departments, medical wards of general hospitals and primary care centres in Karachi, Lahore, Rawalpindi, Peshawar, and Quetta, Pakistan. Patients presenting after a self-harm episode (n = 901) to participating recruitment sites were assessed and randomised (1:1) to one of the two arms; CMAP with enhanced treatment as usual (E-TAU) or E-TAU. The intervention (CMAP) is a manual-assisted, cognitive behaviour therapy (CBT)-informed problem-focused therapy, comprising six one-to-one sessions delivered over three months. Repetition of self-harm at 12-month post-randomisation was the primary outcome and secondary outcomes included suicidal ideation, hopelessness, depression, health-related quality of life (QoL), coping resources, and level of satisfaction with service received, assessed at baseline, 3-, 6-, 9-, and 12-month post-randomisation. The trial is registered on ClinicalTrials.gov. NCT02742922 (April 2016). RESULTS: We screened 3786 patients for eligibility and 901 eligible, consented patients were randomly assigned to the CMAP plus E-TAU arm (n = 440) and E-TAU arm (N = 461). The number of self-harm repetitions for CMAP plus E-TAU was lower (n = 17) compared to the E-TAU arm (n = 23) at 12-month post-randomisation, but the difference was not statistically significant (p = 0.407). There was a statistically and clinically significant reduction in other outcomes including suicidal ideation (- 3.6 (- 4.9, - 2.4)), depression (- 7.1 (- 8.7, - 5.4)), hopelessness (- 2.6 (- 3.4, - 1.8), and improvement in health-related QoL and coping resources after completion of the intervention in the CMAP plus E-TAU arm compared to the E-TAU arm. The effect was sustained at 12-month follow-up for all the outcomes except for suicidal ideation and hopelessness. On suicidal ideation and hopelessness, participants in the intervention arm scored lower compared to the E-TAU arm but the difference was not statistically significant, though the participants in both arms were in low-risk category at 12-month follow-up. The improvement in both arms is explained by the established role of enhanced care in suicide prevention. CONCLUSIONS: Suicidal ideation is considered an important target for the prevention of suicide, therefore, CMAP intervention should be considered for inclusion in the self-harm and suicide prevention guidelines. Given the improvement in the E-TAU arm, the potential use of brief interventions such as regular contact requires further exploration.

IMPACT smoking cessation support for people with severe mental illness in South Asia (IMPACT 4S): A protocol for a randomised controlled feasibility trial of a combined behavioural and pharmacological support intervention.

INTRODUCTION: The prevalence of smoking is high among people living with severe mental illness (SMI). Evidence on feasibility, acceptability and effectiveness of smoking cessation interventions among smokers with SMI is lacking, particularly in low- and middle-income countries. We aim to test the feasibility and acceptability of delivering an evidence-based intervention,i.e., the IMPACT smoking cessation support for people with severe mental illness in South Asia (IMPACT 4S) intervention that is a combination of behavioural support and smoking cessation pharmacotherapies among adult smokers with SMI in India and Pakistan. We will also test the feasibility and acceptability of evaluating the intervention in a randomised controlled trial. METHODS: We will conduct a parallel, open label, randomised controlled feasibility trial among 172 (86 in each country) adult smokers with SMI in India and Pakistan. Participants will be allocated 1:1 to either Brief Advice (BA) or the IMPACT 4S intervention. BA comprises a single five-minute BA session on stopping smoking. The IMPACT 4S intervention comprises behavioural support delivered in upto 15 one-to-one, face-to-face or audio/video, counselling sessions, with each session lasting between 15 and 40 minutes; nicotine gum and/or bupropion; and breath carbon monoxide monitoring and feedback. Outcomes are recruitment rates, reasons for ineligibility/non-participation/non-consent of participants, length of time required to achieve required sample size, retention in study and treatments, intervention fidelity during delivery, smoking cessation pharmacotherapy adherence and data completeness. We will also conduct a process evaluation. RESULTS: Study will address- uncertainty about feasibility and acceptability of delivering smoking cessation interventions, and ability to conduct smoking cessation trials, among adult smokers with SMI in low- and middle-income countries. CONCLUSIONS: This is to inform further intervention adaptation, and the design and conduct of future randomised controlled trials on this topic. Results will be disseminated through peer-review articles, presentations at national, international conferences and policy-engagement forums. TRIAL REGISTRATION: ISRCTN34399445 (Updated 22/03/2021), ISRCTN Registry https://www.isrctn.com/.

A Case Study of Depression in High Achieving Students Associated With Moral Incongruence, Spiritual Distress, and Feelings of Guilt.

Psychosocial and cultural factors play an important, but often neglected, role in depression in young individuals. In this article, we present two cases of young, educated males with major depressive disorder and prominent themes of guilt and spiritual distress. We explore the relationship between moral incongruence, spiritual distress, and feelings of guilt with major depressive episodes by presenting two cases of depression in young individuals who were high-achieving students. Both cases presented with low mood, psychomotor slowing, and selective mutism. Upon detailed history, spiritual distress and feelings of guilt due to internet pornographic use (IPU) and the resulting self-perceived addiction and moral incongruence were linked to the initiation and progression of major depressive episodes. The severity of the depressive episode was measured using the Hamilton Depression Scale (HAM-D). Themes of guilt and shame were measured using the State of Guilt and Shame Scale (SSGS). High expectations from the family were also a source of stress. Hence, it is important to keep these factors in mind while managing mental health problems in young individuals. Late adolescence and early adulthood are periods of high stress and vulnerabe to mental illness. Psychosocial determinants of depression in this age group generally go unexplored and unaddressed leading to suboptimal treatment, particularly in developing countries. Further research is needed to assess the importance of these factors and to determine ways to mitigate them.

Differential Treatment Responses in Pakistani Schizophrenia Samples: Correlation with Sociodemographic Parameters, Drug Addiction, Attitude to the Treatment and Antipsychotic Agents.

Schizophrenia patients demonstrate variations in response to different therapies that are currently being used for the treatment of disorders, such as augmentation therapy (ECT or mood stabilizer) and combination therapy (with antipsychotics). These therapies are also used to treat schizophrenia patients in Pakistan; however, patients show poor overall response. Therefore, this study was conducted to investigate the association between the patients' response to treatment and the use of antipsychotic agents, with variability in overall response, within different groups of patients. Methods: We conducted a retrospective study that included schizophrenia subjects (N = 200) belonging to different age groups, ethnicities, and regions from different outpatient and inpatient departments in psychiatric institutes located in different cities of Pakistan. These patients were assessed for their response to treatment therapies and categorized into four groups (non-responders (N-R), slow response (S-R), patients with relapse, and completely recovered patients (C-R)) according to their responses. Results: The final analysis included 200 subjects, of which 73.5% were males. Mean age was 34 ± 10 years. Percentage of N-R was 5%, S-R was 42%, patients with relapse were 24%, and C-R was 1.5%. The generalized linear regression model shows a significant association between medication response and age (p = 0.0231), age of onset (p = 0.0086), gender (p = 0.005), and marital status (p = 0.00169). Variability within the medication responses was a result of the treatment regime followed. Antipsychotic agents were significantly associated with the treatment response (p = 0.00258, F = 4.981) of the patients. Significant variation was also observed in the treatment response (p = 0.00128) of the patients that were given augmentation therapy as well as combination therapy. Conclusion: The data suggests proper monitoring of patients' behavior in response to treatment therapies to implement tailored interventions. Despite several genetic studies supporting the heritability of schizophrenia, an insignificant association between characteristic features and family history might have been due to the limited sample size, suggesting collaborative work with massive sample sizes.

Use of Escitalopram for pseudobulbar affect following severe traumatic.

Those who have suffered from traumatic brain injury (TBI) often develop behavioural, affective, and cognitive complications. Some might experience episodes of involuntary and/or exaggerated laughter and crying. This condition is commonly known as 'pseudobulbar affect'(PBA) and leads to anger, frustration, and social disability. This case report presents the use of low-dose Escitalopram in an individual suffering from agitation and PBA following severe TBI (sTBI). It emphasises the importance of adopting a holistic approach in the treatment of such individuals with appropriate attention paid to factors such as cognitive and behavioural impairment, and caregiver distress.

Prevalence of physical health conditions and health risk behaviours in people with severe mental illness in South Asia: multi-country cross-sectional survey.

BACKGROUND: People with severe mental illness (SMI) die earlier than the general population, primarily because of physical disorders. AIMS: We estimated the prevalence of physical health conditions, health risk behaviours, access to healthcare and health risk modification advice in people with SMI in Bangladesh, India and Pakistan, and compared results with the general population. METHOD: We conducted a cross-sectional survey in adults with SMI attending mental hospitals in Bangladesh, India and Pakistan. Data were collected on non-communicable diseases, their risk factors, health risk behaviours, treatments, health risk modification advice, common mental disorders, health-related quality of life and infectious diseases. We performed a descriptive analysis and compared our findings with the general population in the World Health Organization (WHO) 'STEPwise Approach to Surveillance of NCDs' reports. RESULTS: We recruited 3989 participants with SMI, of which 11% had diabetes, 23.3% had hypertension or high blood pressure and 46.3% had overweight or obesity. We found that 70.8% of participants with diabetes, high blood pressure and hypercholesterolemia were previously undiagnosed; of those diagnosed, only around half were receiving treatment. A total of 47% of men and 14% of women used tobacco; 45.6% and 89.1% of participants did not meet WHO recommendations for physical activity and fruit and vegetable intake, respectively. Compared with the general population, people with SMI were more likely to have diabetes, hypercholesterolemia and overweight or obesity, and less likely to receive tobacco cessation and weight management advice. CONCLUSIONS: We found significant gaps in detection, prevention and treatment of non-communicable diseases and their risk factors in people with SMI.

Effect of Adjunctive Simvastatin on Depressive Symptoms Among Adults With Treatment-Resistant Depression: A Randomized Clinical Trial.

Importance: Immune-metabolic disturbances have been implicated in the pathophysiology of major depressive disorder and may be more prominent in individuals with treatment-resistant depression (TRD). Preliminary trials suggest that lipid-lowering agents, including statins, may be useful adjunctive treatments for major depressive disorder. However, no adequately powered clinical trials have assessed the antidepressant efficacy of these agents in TRD. Objective: To assess the efficacy and tolerability of adjunctive simvastatin compared with placebo for reduction of depressive symptoms in TRD. Design, Setting, and Participants: This 12-week, double-blind, placebo-controlled randomized clinical trial was conducted in 5 centers in Pakistan. The study involved adults (aged 18-75 years) with a Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) major depressive episode that had failed to respond to at least 2 adequate trials of antidepressants. Participants were enrolled between March 1, 2019, and February 28, 2021; statistical analysis was performed from February 1 to June 15, 2022, using mixed models. Intervention: Participants were randomized to receive standard care plus 20 mg/d of simvastatin or placebo. Main Outcomes and Measures: The primary outcome was the difference between the 2 groups in change in Montgomery-Åsberg Depression Rating Scale total scores at week 12. Secondary outcomes included changes in scores on the 24-item Hamilton Rating Scale for Depression, the Clinical Global Impression scale, and the 7-item Generalized Anxiety Disorder scale and change in body mass index from baseline to week 12. C-reactive protein and plasma lipids were measured at baseline and week 12. Results: A total of 150 participants were randomized to simvastatin (n = 77; median [IQR] age, 40 [30-45] years; 43 [56%] female) or placebo (n = 73; median [IQR] age, 35 [31-41] years; 40 [55%] female). A significant baseline to end point reduction in Montgomery-Åsberg Depression Rating Scale total score was observed in both groups and did not differ significantly between groups (estimated mean difference for simvastatin vs placebo, -0.61; 95% CI, -3.69 to 2.46; P = .70). Similarly, there were no significant group differences in any of the secondary outcomes or evidence for differences in adverse effects between groups. A planned secondary analysis indicated that changes in plasma C-reactive protein and lipids from baseline to end point did not mediate response to simvastatin. Conclusions and Relevance: In this randomized clinical trial, simvastatin provided no additional therapeutic benefit for depressive symptoms in TRD compared with standard care. Trial Registration: ClinicalTrials.gov Identifier: NCT03435744.

Improving psychosocial distress for young adolescents in rural schools of Pakistan: study protocol of a cluster randomised controlled trial.

INTRODUCTION: Emotional problems are leading contributors to health burden among adolescents worldwide. There is an urgent need for evidence-based psychological interventions for young people. This study aims to evaluate the effectiveness of a school-based, group psychological intervention, Early Adolescent Skills for Emotions (EASE) developed by the WHO to improve psychosocial distress in Pakistani adolescents. METHOD AND ANALYSIS: A two-arm, single-blinded, cluster randomised controlled trial, with a wait-list control arm is being conducted in school settings of rural Pakistan. Forty eligible public-school clusters have been randomised (stratified by gender) on a 1:1 allocation ratio into intervention (n=20) and control arm (n=20). Following informed consent, 564 adolescents with psychosocial distress (Youth-reported Paediatric Symptoms Checklist, cut-off ≥28) from 40 schools have been enrolled into the trial (14±3 average cluster size) between 2 November 2021 and 30th November 2021. Participants in the intervention arm will receive EASE in 7-weekly adolescents and 3-biweekly caregivers group sessions in schools. The adolescent sessions involve the components of psychoeducation, stress management, behavioural activation, problem-solving and relapse prevention. Caregivers will receive training to learn and implement active listening; spending quality time and using praise as a strategy to help their children. The primary outcome is reduction in psychosocial distress at 3 months postintervention. Secondary outcomes include symptoms of depression and anxiety, caregiver-adolescent relationship and caregivers' well-being. Outcomes will be assessed at baseline, immediate 1 week and 3-months postintervention. Qualitative process evaluation will explore barriers and facilitators to programme implementation in low-resource school settings. ETHICS: Ethics approval has been obtained from Central Ethics Committee of University of Liverpool, UK, Ethics Review Committee of WHO Geneva and from the Institutional Review Board of Human Development Research Foundation (HDRF), Pakistan. DISSEMINATION: The findings of the study will be disseminated by WHO and through peer-reviewed publications. TRIAL REGISTRATION NUMBER: ISRCTN17755448.

Feasibility and acceptability of a multicomponent, group psychological intervention for adolescents with psychosocial distress in public schools of Pakistan: a feasibility cluster randomized controlled trial (cRCT).

BACKGROUND: Child and adolescent mental health problems are a global public mental health priority. However, there is a lack of evidence-based scalable psychological interventions for adolescents living in low resource settings. This trial was designed to evaluate the feasibility and acceptability of delivering the World Health Organization's Early Adolescent Skills for Emotions (EASE) intervention at public schools in a rural sub-district in Rawalpindi, Pakistan. METHODS: A two arm, single blinded, feasibility cluster randomized controlled trial with mixed-methods evaluation was conducted with 59 adolescents and their caregivers from 8 public schools. In the 4 intervention arm schools, 6 non-specialist facilitators delivered the culturally-adapted EASE group sessions to the adolescents (n = 29) and their caregivers with desired fidelity under the supervision of in-country supervisors. RESULTS: The participation rate of adolescents in the intervention sessions was 83%. The intervention strategies were implemented by the adolescents. However, attending biweekly sessions at schools was challenging for caregivers with only 50% caregivers attending the sessions. CONCLUSIONS: The results of this study support the feasibility and acceptability of delivering this culturally adapted intervention through non-specialist facilitators in school settings in Pakistan and pave the way to conduct a fully powered cluster randomized controlled trial to test the effectiveness of intervention to improve psychological outcomes in adolescents. Trial registration Trial registered with Clinicaltrials.gov prospectively; NCT04254393.

Youth Culturally adapted Manual Assisted Problem Solving Training (YCMAP) in Pakistani adolescent with a history of self-harm: protocol for multicentre clinical and cost-effectiveness randomised controlled trial.

INTRODUCTION: Suicide is a global health concern. Sociocultural factors have an impact on self-harm and suicide rates. In Pakistan, both self-harm and suicide are considered as criminal offence's and are condemned on both religious and social grounds. The proposed intervention 'Youth Culturally Adapted Manual Assisted Problem Solving Training (YCMAP)' is based on principles of problem-solving and cognitive-behavioural therapy. YCMAP is a brief, culturally relevant, scalable intervention that can be implemented in routine clinical practice if found to be effective. METHOD AND ANALYSIS: A multicentre rater blind randomised controlled trial to evaluate the clinical and cost-effectiveness of YCMAP including a sample of 652 participants, aged 12-18 years, presenting to general physicians/clinicians, emergency room after self harm or self referrals. We will test the effectiveness of 8-10 individual sessions of YCMAP delivered over 3 months compared with treatment as usual. Primary outcome measure is repetition of self-harm at 12 months. The seconday outcomes include reduction in suicidal ideation, hopelessness and distress and improvement in health related quality of life. Assessments will be completed at baseline, 3, 6, 9 and 12 months postrandomisation. The nested qualitative component will explore perceptions about management of self-harm and suicide prevention among adolescents and investigate participants' experiences with YCMAP. The study will be guided by the theory of change approach to ensure that the whole trial is centred around needs of the end beneficiaries as key stakeholders in the process. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Ethics Committee of University of Manchester, the National Bioethics Committee in Pakistan. The findings of this study will be disseminated through community workshops, social media, conference presentations and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04131179.

Knowledge and Response to the COVID-19 Pandemic in People With Severe Mental Illness in Bangladesh and Pakistan: A Cross-Sectional Survey.

BACKGROUND: People with severe mental illnesses (SMIs) are likely to face disproportionate challenges during a pandemic. They may not receive or be able to respond to public health messages to prevent infection or to limit its spread. Additionally, they may be more severely affected, particularly in low- and middle-income countries. METHODS: We conducted a telephone survey (May-June 2020) in a sample of 1,299 people with SMI who had attended national mental health institutes in Bangladesh and Pakistan before the pandemic. We collected information on top worries, socioeconomic impact of the pandemic, knowledge of COVID-19 (symptoms, prevention), and prevention-related practices (social distancing, hygiene). We explored the predictive value of socio-demographic and health-related variables for relative levels of COVID-19 knowledge and practice using regularized logistic regression models. FINDINGS: Mass media were the major source of information about COVID-19. Finances, employment, and physical health were the most frequently mentioned concerns. Overall, participants reported good knowledge and following advice. In Bangladesh, being female and higher levels of health-related quality of life (HRQoL) predicted poor and better knowledge, respectively, while in Pakistan being female predicted better knowledge. Receiving information from television predicted better knowledge in both countries. In Bangladesh, being female, accessing information from multiple media sources, and better HRQoL predicted better practice. In Pakistan, poorer knowledge of COVID-19 prevention measures predicted poorer practice. CONCLUSION: Our paper adds to the literature on people living with SMIs and their knowledge and practices relevant to COVID-19 prevention. Our results emphasize the importance of access to mass and social media for the dissemination of advice and that the likely gendered uptake of both knowledge and practice requires further attention.

Debate: Child and adolescent mental health services in Pakistan; Do we need in-patient mental health facilities for children and young people?

Depression and anxiety are leading causes of morbidity in children and adolescents worldwide. In Pakistan, young people are exposed to many chronic adversities including violence, social and economic inequalities, and are at greater risk of developing mental health problems. Yet there is a lack of trained human resources, in-patient child and adolescent mental healthcare facilities, and training opportunities in child and adolescent psychiatry and mental health in Pakistan. Given the poor economic condition of the country, which has been made even worse by the COVID-19 pandemic, it is very unlikely that dedicated resources will be made available in near future to develop specialist child and adolescent mental health services in Pakistan. To bridge this treatment gap, we propose a multitiered, transdiagnostic, task-shifting strategy-based model for child and adolescent mental health services in Pakistan.

Technology-Assisted Teachers' Training to Promote Socioemotional Well-Being of Children in Public Schools in Rural Pakistan.

BACKGROUND: The World Health Organization's (WHO) Eastern Mediterranean Regional Office (EMRO) developed a school mental health program (SMHP) to help reduce the burden of youth mental health problems. Designed in collaboration with international consultants, the SMHP draws on evidence-based interventions to train personnel to identify students in need, respond therapeutically, and engage families in seeking care. METHODS: Teams from Pakistan, Egypt, Iran, and Jordan collaborated with the WHO EMRO and British and U.S. universities to form the School Health Implementation Network: Eastern Mediterranean Region (SHINE), a National Institute of Mental Health-funded global mental health hub. SHINE partners used a "theory of change" process to adapt the SMHP to be more readily adopted by school personnel and replicated with fidelity. The adapted SMHP more directly addresses teachers' priorities and uses technology to facilitate training. RESULTS: A cluster-randomized implementation effectiveness trial enrolling 960 children ages 8-13 in 80 Pakistani schools will test the adapted SMHP against the original. Children who screen positive on first the teacher and subsequently the parent Strengths and Difficulties Questionnaires (SDQs) will be enrolled and tracked for 9 months. The primary trial outcome is reduction in parent-rated SDQ total difficulties scores. Secondary outcomes include children's well-being, academic performance, absenteeism, and perceived stigma; parent-teacher interaction; teachers' self-efficacy and subjective well-being; and school environment. Implementation outcomes include change in teachers' behavior and sense of program acceptability, cultural appropriateness, feasibility, penetration, and sustainability. NEXT STEPS: The trial began in October 2019, and the expected completion date is March 2021. Outcomes will inform dissemination of the SMHP in Pakistan and elsewhere.