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.

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.

An integrated parenting intervention for maternal depression and child development in a low-resource setting: Cluster randomized controlled trial.

BACKGROUND: Rates of depression among Pakistani mothers are high, leading to poor developmental outcomes in their children. This study tested the effectiveness of a manualized integrated parenting program; Learning through Play Plus (LTP+) for maternal depression in Karachi, Pakistan. METHODS: A cluster randomized control trial conducted from January 2014 to December 2015 across 120 villages in Karachi. A total of 774 depressed mothers aged 18-44 years with children aged 0-30 months old, were included. Villages were randomized to receive LTP+ added to treatment as usual (TAU) or TAU alone. Primary outcomes were severity of maternal depression at 3 and 6 months measured by the Edinburgh Postnatal Depression Scale and child socio-emotional development at 6 months measured by the Ages and Stages Questionnaire (ASQ). Secondary outcomes included maternal anxiety, quality of life, social support, parenting competence, and knowledge about child development. RESULTS: Mothers in the LTP+ group reported significantly lower depression scores compared to those in the TAU group (6.6 vs. 13.8, effect size [ES]: -7.2; 95% confidence interval [CI]: -8.2, -6.1) at 3 and 6 months (7.2 vs. 12.00; ES: -4.6; 95% CI: -5.9, -3.4). Child socio-emotional development at 6 months was significantly better in the LTP+ group on all domains of the ASQ. There were also statistically significant improvements on all secondary outcomes at 3- and 6-month follow-up. CONCLUSION: In low-resource settings like Pakistan, low-cost integrated parenting interventions delivered by lay health workers can provide effective treatment for depressed mothers, leading to improvements in child development.

Depression and suicidal ideation in schizophrenia spectrum disorder: a cross-sectional study from a lower middle-income country.

OBJECTIVES: Depression has long been considered a significant feature of schizophrenia and is associated with more frequent psychotic episodes, increased service utilisation, substance misuse, poor quality of life and completed suicide. However, there is a distinct lack of literature on this comorbidity from low- and middle-income countries or non-western cultural backgrounds. METHODS: This is a cross-sectional analysis of baseline data from a large randomised controlled trial, examining the prevalence of depression and suicidal ideation in patients with schizophrenia spectrum disorder. A total of 298 participants were recruited from inpatient and outpatient psychiatric units in Karachi, Pakistan. Participants completed the Calgary Depression Scale for Schizophrenia (CDSS), Positive and Negative Syndrome Scale (PANSS), Euro Qol (EQ-5D) and Social Functioning Scale (SFS). RESULTS: Data indicate that 36% of participants in the study were depressed and 18% endorsed suicidal ideation. Depression was associated with higher positive symptom scores and reduced quality of life, but no significant difference in negative symptoms and social functioning. CONCLUSIONS: Depression and suicidal ideation are prevalent in Pakistani patients diagnosed with schizophrenia spectrum disorder. Evaluation of depressive symptoms in this group may help identify individuals at higher risk of completed suicide, allowing for targeted interventions to improve outcomes.Key pointsTo our knowledge, this is the first study describing the prevalence of depression and suicidal ideation in individuals with schizophrenia from Pakistan.Our data indicate that 36% of individuals with schizophrenia in our sample were depressed and 18% endorsed suicidal ideation.Depression in schizophrenia was associated with poorer quality of life and higher positive symptom burden.This study adds to the scarce literature from low- and middle-income countries where the burden of mental illness is great and where the majority of suicide deaths occur.Addressing social inequality, food insecurity, high rates of unemployment and low levels of literacy in these settings may have a profound effect on population mental health and suicide risk.

Culturally adapted family intervention for schizophrenia in Pakistan: a feasibility study.

OBJECTIVES: To establish feasibility and acceptability of a Culturally adapted Family Intervention (CulFI) that was developed using an empirically derived conceptual framework in Pakistan. METHODS: A rater-blind, randomised trial to evaluate the feasibility and acceptability of delivering CulFI compared to treatment as usual in Karachi, Pakistan. Indicators of feasibility included evaluation of recruitment rates, retention and randomisation. We also evaluated the acceptability of the intervention and trial procedures. RESULTS: Excellent recruitment and retention rates informed the feasibility of the intervention. CulFI had more than a 90% participant attendance of 8-10 sessions and retained more than 90% who commenced in the intervention. Eighty percent of those who initially provided consent were willing to be randomised and the quality of CulFI was rated as good to excellent by 85.7% of participants. CONCLUSIONS: Importantly, this study determines that pathways into a psychosocial intervention can be established in Pakistan. A combination of factors contribute to low levels of access to psychiatric care including different explanatory models of illness, small numbers of trained staff, limited resources and reliance on traditional healers. These results support the feasibility, acceptability and merit of conducting a full-scale trial of CulFI in comparison with standard care.ClinicalTrials.gov Identifier: NCT02167347KEY POINTSThe significant treatment gap in LMICs leaves families providing much of the care for people with schizophrenia.There is limited evidence from LMICs supporting the effectiveness and feasibility of psychosocial interventions more broadly, and family interventions specifically.This study adds to the scarce literature and demonstrates that pathways into delivering psychosocial interventions can be established in Pakistan.The results of this trial support the feasibility and acceptability of a Culturally adapted Family Intervention (CulFI) for schizophrenia patients and their families in PakistanA full-scale trial of CulFI in comparison with standard care is warranted to determine clinical and cost-effectiveness.

Cognitive function in early psychosis patients from a lower middle-income country.

OBJECTIVES: To establish evidence of cognitive changes in early psychosis (EP) patients compared to healthy controls (HC) in Pakistan. METHODS: Fifty-one participants with EP were recruited from psychiatric units in Karachi and Rawalpindi, Pakistan and matched with 51 HC. Neurocognitive domains were assessed using standardised neuropsychological tests [the Stroop test, block design, Matrix Reasoning, picture completion, object assembly, oral fluency, memory for design, Coughlan learning task (verbal and visual)]. RESULTS: EP patients had higher scores than controls for both Stroop tests (T1: EP = 122 HC = 65, p <.001; T2: EP = 190 HC = 153, p = .007) and memory for design test (EP = 10 HC = 3, p = .005). EP group had lower values for block design (EP = 4, HC = 11, p = .01), category fluency (EP = 18.9, HC = 26.1, p < .001), Coughlan verbal tasks (EP = 36.4 NC = 51.5, p < .001), matrix reasoning (EP = 4 NC = 10, p < .001), picture completion (EP = 4 NC = 6, p = .003) and object assembly (EP = 10.7, HC = 15.5, p = .002). There were limited significant associations between cognitive performance and PANSS scores. CONCLUSIONS: Reduced cognitive performance was found across multiple domains in Pakistani EP patients, which suggests that impaired cognitive performance is homogenous in patients with schizophrenia, regardless of ethnicity.

Pilot randomised controlled trial of culturally adapted cognitive behavior therapy for psychosis (CaCBTp) in Pakistan.

BACKGROUND: Evidence for efficacy of cognitive-behavioural therapy (CBT) in treatment of schizophrenia is growing. CBT is effective and cost efficient in treating positive and negative symptoms. To effectively meet the needs of diverse cultural groups, CBT needs to be adapted to the linguistic, cultural and socioeconomic context. We aimed to assess the feasibility, efficacy and acceptability of a culturally adapted CBT for treatment of psychosis (CaCBTp) in a low-income country. METHODS: Rater-blind, randomised, controlled trial of the use of standard duration CBT in patients with psychosis from a low-income country. Participants with a ICD-10 diagnosis of psychosis were assessed using Positive and Negative Syndrome Scale for Schizophrenia (PANSS), Psychotic Symptom Rating Scales (PSYRATS), and the Schedule for Assessment of Insight (SAI) (baseline, 3 months and 6 months). They were randomized into the intervention group (n = 18) and Treatment As Usual (TAU) group (n = 18). The intervention group received 12 weekly sessions of CaCBTp. RESULTS: The CaCBTp group had significantly lower scores on PANSS Positive (p = 0.02), PANSS Negative (p = 0.045), PANSS General Psychopathology (p = 0.008) and Total PANSS (p = 0.05) when compared to TAU at three months. They also had low scores on Delusion Severity Total (p = 0.02) and Hallucination Severity Total (p = 0.04) of PSYRATS, as well as higher scores on SAI (p = 0.01) at the same time point. At six months only the improvement in PANSS positive scores (p = 0.045) met statistical significance.. CONCLUSIONS: It is feasible to offer CaCBTp as an adjunct to TAU in patients with psychosis, presenting to services in a lower middle-income country. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02202694 (Retrospectively registered).

Detecting maternal depression in a low-income country: comparison of the self-reporting questionnaire and the edinburgh postnatal depression scale.

OBJECTIVE: To validate the Self-Reporting Questionnaire (SRQ-20) and the Edinburgh Postnatal Depression Scale (EPDS) against the Clinical Interview Schedule-Revised (CIS-R). DESIGN: Two-phase design. SUBJECTS AND METHODS: 664 mothers were approached, 601 of them completed the EPDS and SRQ questionnaires. The CIS-R was administered to confirm the diagnosis for depression. The diagnostic accuracy was compared using the receiver operating characteristic analysis. RESULTS: At the threshold of 11, the SRQ had better sensitivity, negative predictive values and positive predictive values compared with the EPDS optimal threshold of 14. CONCLUSION: Both measures (EPDS and SRQ) have adequate validity to screen for depression in mothers in Pakistan. However, the SRQ performed better, with participants finding it easy to understand. The scales can be of great value to detect maternal depression in primary care and pediatric settings in low-income countries.

Effectiveness of Learning through Play Plus (LTP Plus) Parenting Intervention on Behaviours of Young Children of Depressed Mothers: A Randomised Controlled Trial.

Evidence has shown that parenting intervention programmes improve parental knowledge, attitudes, and practices, which helps in promoting child development. This study aims to examine the effectiveness of parenting intervention in improving child behaviours. This is a secondary analysis of data from a cluster-randomised controlled trial with depressed mothers aged 18-44 years with a child aged 0 to 36 months. This paper reports findings from the dataset of participants with a child aged between 24 and 36 months. Villages (n = 120) were randomised into either of two arms: learning through play plus (LTP Plus) or treatment as usual (TAU). LTP Plus is a 10-session, group parenting intervention integrated with cognitive behaviour therapy, delivered over 3 months. This secondary analysis reports findings on the Eyberg Child Behaviour Inventory (ECBI) and the Home Observation for Measurement of the Environment (HOME). Findings show a significant improvement in child behaviour (ECBI) scores (p < 0.011) and HOME scores (p < 0.001) in the intervention group compared to TAU at 3-month follow-up. In a low-resource setting, low-cost group parenting intervention delivered by community health workers has the potential to improve child behaviours and quality of the home environment. Parenting interventions aimed at improving child behavioural problems can have significant implications for the child, family, and broader societal outcomes. Addressing behavioural problems in early years, parenting interventions can potentially reduce long-term consequences and costs associated with untreated child behavioural issues.

Adverse Events Reporting in Digital Interventions Evaluations for Psychosis: A Systematic Literature Search and Individual Level Content Analysis of Adverse Event Reports.

BACKGROUND: Digital health interventions (DHIs) have significant potential to upscale treatment access to people experiencing psychosis but raise questions around patient safety. Adverse event (AE) monitoring is used to identify, record, and manage safety issues in clinical trials, but little is known about the specific content and context contained within extant AE reports. This study aimed to assess current AE reporting in DHIs. STUDY DESIGN: A systematic literature search was conducted by the iCharts network (representing academic, clinical, and experts by experience) to identify trials of DHIs in psychosis. Authors were invited to share AE reports recorded in their trials. A content analysis was conducted on the shared reports. STUDY RESULTS: We identified 593 AE reports from 18 DHI evaluations, yielding 19 codes. Only 29 AEs (4.9% of total) were preidentified by those who shared AEs as being related to the intervention or trial procedures. While overall results support the safety of DHIs, DHIs were linked to mood problems and psychosis exacerbation in a few cases. Additionally, 27% of studies did not report information on relatedness for all or at least some AEs; 9.6% of AE reports were coded as unclear because it could not be determined what had happened to participants. CONCLUSIONS: The results support the safety of DHIs, but AEs must be routinely monitored and evaluated according to best practice. Individual-level analyses of AEs have merit to understand safety in this emerging field. Recommendations for best practice reporting in future studies are provided.

Economic burden of mental illness in Pakistan: an estimation for the year 2020 from existing evidence.

This report is based on the extrapolation to 2020 of data on the economic burden of mental illnesses in Pakistan in 2006. Given the resultant estimated high economic burden of mental illness in the country (£2.97 billion in 2020), we advocate a revised budget allocation to mental healthcare. As a resource-scarce nation that is entangled in natural disasters, Pakistan needs cost-effective psychological interventions such as culturally adapted manual-assisted problem-solving training (C-MAP) for the prevention of self-harm and suicide and to move towards attaining the United Nations' Sustainable Development Goals (SDGs). Although government has taken initiatives to support healthcare services (such as the Sehat Sahulat Program for universal health coverage), there is still a need to implement a cost-effective national digital model for mental healthcare such as the Agha Khan Development Network Digital Health Programme.

Exploring chronic pain related attentional experiences, distress and coping strategies among Arabic-speaking individuals in Jordan and the United Kingdom.

Introduction: The lived experiences of chronic pain (CP) among Arabic-speaking populations remain underexplored. A better understanding of these experiences and their associations with attention difficulties, coping mechanisms, and treatment options could lead to improved support for this group. Methods: This qualitative study utilised a descriptive design and involved one-to-one interviews with 51 participants with CP who had just completed two attention tasks. Interviews were conducted using a semi-structured topic guide, transcribed verbatim and translated from Arabic to English before agreeing on the coding framework. Themes and subthemes were extracted using a framework analysis approach. Results: The study identified six main themes: Factors contributing towards developing or exacerbating CP, the impact of CP on psychosocial functions, including attention, the perceived role of social support, coping strategies for managing CP, perceptions about available treatments and recommendations for interventions. Discussion: CP significantly impacts individuals' physical and psychosocial functions, and it is reciprocally associated with attentional difficulties. Despite using various approaches to manage their CP, none of the participants used psychological interventions or counselling. Understanding the diverse impacts of CP and the coping strategies employed to develop culturally sensitive interventions, review current related policies, and improve healthcare services is crucial to managing CP among this population.

Burden of mental disorders by gender in Pakistan: analysis of Global Burden of Disease Study data for 1990-2019.

AIMS AND METHOD: We aimed to examine the burden of mental disorders in Pakistan over the past three decades. We used the crude data of disability-adjusted life-years (DALYs) obtained from the Global Burden of Disease Study database (1990-2019) to represent burden. Data were retrieved on 26 January 2021. Data for adults of reproductive age (aged 15-49 years) were analysed to discuss and interpret the disease burden. An analysis was conducted on total DALYs separately for the genders for ten mental disorders reported in Pakistan. RESULTS: DALYs increased drastically with the onset of reproductive age. Depressive disorder was the most reported mental disorder, contributing 3.13% (95% CI 2.25-4.24) of total DALYs, and varied significantly between genders: females 3.89% (95% CI 2.73-5.29) versus males 2.37% (95% CI 1.62-3.25). CLINICAL IMPLICATIONS: A nationwide high-quality epidemiological surveillance system should be implemented to monitor mental disorders and offer culturally appropriate preventive services.

Clinicians', patients' and carers' perspectives on borderline personality disorder in Pakistan: A mixed methods study protocol.

Borderline Personality Disorder (BPD) is a condition characterised by significant social and occupational impairment and high rates of suicide. In high income countries, mental health professionals carry negative attitudes towards patients with BPD, find it difficult to work with patients with BPD, and even avoid seeing these patients. Negative attitudes and stigma can cause patients to fear mistreatment by health care providers and create additional barriers to care. Patients' self-stigma and illness understanding BPD also affects treatment engagement and outcomes; better knowledge about mental illness predicts intentions to seek care. The perspectives of mental health clinicians and patients on BPD have not been researched in the Pakistani setting and likely differ from other settings due to economic, cultural, and health care system differences. Our study aims to understand the attitudes of mental health clinicians towards patients with BPD in Pakistan using a self-report survey. We also aim to explore explanatory models of illness in individuals with BPD and their family members/carers using a Short Explanatory Model Interview (SEMI). The results of this study are important as we know attitudes and illness understanding greatly impact care. Results of this study will help guide BPD-specific training for mental health clinicians who care for patients with BPD and help inform approaches to interventions for patients with BPD in Pakistan.

Supporting Depressed Mothers of Young Children with Intellectual Disability: Feasibility of an Integrated Parenting Intervention in a Low-Income Setting.

As a lifelong condition, intellectual disability (ID) remains a public health priority. Parents caring for children with ID experience serious challenges to their wellbeing, including depression, anxiety, stress and health-related quality of life. Integrated parenting interventions, which have been well evidenced for depressed mothers, may also effectively support depressed parents with a child with ID in low-resource settings such as Pakistan, and in turn optimise child outcomes. We conducted a mixed-method rater-blind feasibility randomised controlled trial, which assessed the feasibility and acceptability of the Learning Through Play in My Own Way Plus (LTP-IMOW Plus) intervention. Mothers who screened positive for depression (n = 26) with a young child (age 3-6 years) with ID were recruited from two low-resource community settings. Participants in the intervention arm (n = 13) received 12 group sessions of LTP-IMOW Plus and others (n = 13) received routine care. The intervention was feasible and acceptable with 100% retention and 100% session attendance. The intervention improved depression, anxiety, parenting stress and child socialisation score outcomes relative to the routine care arm. The framework utilised to analyse the qualitative interviews with seven participants at pre-intervention identified a range of struggles experienced by the mothers, and at post-intervention, found improved knowledge of child development and practices, improved mother-child relationships, recommendations for the intervention and perceived practical barriers and facilitators. The findings highlight the prospects for a clinical and cost-effective trial of an integrated parenting intervention to manage long-term parental mental health needs and improve child outcomes.

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.

Antecedents, clinical and psychological characteristics of a large sample of individuals who have self-harmed recruited from primary care and hospital settings in Pakistan.

BACKGROUND: Suicide is one of the leading causes of mortality worldwide, and the majority of suicide deaths occur in low- and middle-income countries. AIMS: To evaluate the demographic and clinical characteristics of individuals who have presented to health services following self-harm in Pakistan. METHOD: This study is a cross-sectional baseline analysis of participants from a large multicentre randomised controlled trial of self-harm prevention in Pakistan. A total of 901 participants with a history of self-harm were recruited from primary care clinics, emergency departments and general hospitals in five major cities in Pakistan. The Beck Scale for Suicide Ideation (BSI), Beck Depression Inventory (BDI), Beck Hopelessness Scale (BHS) and Suicide Attempt Self Injury Interview assessment scales were completed. RESULTS: Most participants recruited were females (n = 544, 60.4%) in their 20s. Compared with males, females had lower educational attainment and higher unemployment rates and reported higher severity scores on BSI, BDI and BHS. Interpersonal conflict was the most frequently cited antecedent to self-harm, followed by financial difficulties in both community and hospital settings. Suicide was the most frequently reported motive of self-harm (N = 776, 86.1%). Suicidal intent was proportionally higher in community-presenting patients (community: N = 318, 96.9% v. hospital: N = 458, 79.9%; P < 0.001). The most frequently reported methods of self-harm were ingestion of pesticides and toxic chemicals. CONCLUSIONS: Young females are the dominant demographic group in this population and are more likely to attend community settings to seek help. Suicidal intent as the motivator of self-harm and use of potentially lethal methods may suggest that this population is at high risk of suicide.

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.

Cost-Effectiveness of a Culturally Adapted Manual-Assisted Brief Psychological Intervention for Self-Harm in Pakistan: A Secondary Analysis of the Culturally Adapted Manual-Assisted Brief Psychological Randomized Controlled Trial.

OBJECTIVES: Self-harm is a serious public health problem. A culturally adapted manual-assisted problem-solving training (C-MAP) intervention improved and sustained a reduction in suicidal ideation, hopelessness, and depression compared with treatment as usual (TAU) alone. Here, we evaluate its cost-effectiveness. METHODS: Patients admitted after an episode of self-harm were randomized individually to either C-MAP plus TAU or TAU alone in Karachi. Improvement in health-related quality-adjusted life-years (QALYs) was measured using the EQ-5D with 3 levels instrument at baseline, 3 months, and 6 months after randomization. The primary economic outcome was health service cost per QALY gained as the incremental cost-effectiveness ratio, based on 2019 US$ and a 6-month time horizon. Nonparametric bootstrapping was used to assess uncertainties and sensitivity analysis to examine the impact of hospitalization costs. RESULTS: A total of 108 and 113 participants were enrolled among the intervention and standard arms, respectively. The intervention resulted in 0.04 (95% confidence interval [CI] 0.00-0.08) more QALYs 6 months after enrolment. The mean cost per participant in the intervention arm was $1001 (95% CI 968-1031), resulting in an incremental cost of the intervention of $640 (95% CI 595-679). The incremental cost-effectiveness ratio for the C-MAP intervention versus TAU was $16 254 (95% CI 7116-99 057) per QALY gained. The probability that C-MAP is cost-effective was between 66% and 83% for cost-effective thresholds between $20 000 and $30 000. Cost-effectiveness results remained robust to sensitivity analyses. CONCLUSIONS: C-MAP may be a valuable self-harm intervention. Further studies with longer follow-up and larger sample sizes are needed to draw reliable conclusions.

Building Resilience Against ViolencE (BRAVE): protocol of a parenting intervention for mothers and fathers with post-traumatic stress disorder in Pakistan.

Background: Prevalence of post-traumatic stress disorder (PTSD) is high in Pakistan both due to natural disasters and ongoing conflicts. Offspring of trauma survivors are at increased risk for mental and physical illnesses. Parental PTSD has been linked to troubled parent-child relationships, behaviour problems, trauma symptoms, and depression in children. This study aims to explore the acceptability, feasibility and indications of the effectiveness of group learning through play plus trauma-focused cognitive behaviour therapy (LTP Plus TF-CBT) for parents experiencing PTSD. Methods/Design: This is a two-arm pilot cluster randomised controlled trial (RCT). We aim to recruit 300 parents with a diagnosis of PTSD. The screening will be done using the Impact of Event Scale-Revised. Diagnosis of PTSD will be confirmed using the Clinician-Administered PTSD Scale-5 (CAPS-5). Union Councils from Peshawar and Karachi will be randomised into either group LTP Plus TF CBT arm or treatment as usual (TAU). The intervention includes 12 sessions of LTP Plus TF-CBT delivered weekly in the first 2 months and then fortnightly in a group setting by trained psychologists. The groups will be co-facilitated by the community health workers (CHWs). Parents will be assessed at baseline and 4th month (end of the intervention), using the Patient Health Questionnaire (PHQ-9), Generalised Anxiety Disorder (GAD-7) Scale, Client Service Receipt Inventory (CSRI), and Ages and Stages Questionnaire (ASQ-3). Discussion: This trial would help build an understanding of the acceptability, feasibility and indications of the effectiveness of a low-cost parenting intervention.