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Background: Suicide is a major public health concern and one of the leading causes of mortality worldwide. People with an at‐risk‐mental‐state (ARMS) for psychosis are more vulnerable to psychiatric co‐morbidity and suicide, however, there are limited data from low‐middle‐income countries. The present study aimed to identify the prevalence of depressive symptoms and suicidal ideation along with sociodemographic and clinical correlates of suicidal ideation in individuals with ARMS from Pakistan. Method: Participants between the age of 16 and 35 years who met the criteria for ARMS based on the Comprehensive Assessment of At‐Risk Mental State (CAARMS), were recruited from the community, general practitioner clinics and psychiatric units across Pakistan (n = 326). Montgomery and Asberg Depression Rating Scale (MADRS) and Social‐Occupational‐Functional‐Assessment‐Scale (SOFAS) were administered to participants. Results: The prevalence of depressive symptoms and suicidal thoughts in the sample at baseline were 91.1% (n = 297) and 61.0% (n = 199), respectively. There were significant mean differences between groups (mean difference [95% CI]; p‐value) without suicidal ideation and with suicidal ideation on measures of MADRS (−5.47 [−7.14, −3.81]; p <.001), CAARMS non‐bizarre ideas (−0.29 [−0.47, −0.11]; p =.002) and perceptual abnormalities (−0.23 [−0.41, −0.04]; p =.015). Conclusion: These findings indicate that suicidal ideation and depressive symptoms are highly prevalent in individuals with ARMS in Pakistan. Given the pivotal developmental stages that ARMS presents, and the poor outcomes associated with co‐morbid depression, there is an urgent need to prioritize the development of low‐cost and scalable evidence‐based interventions to address psychiatric comorbidity and suicidality in the ARMS population in Pakistan. [ABSTRACT FROM AUTHOR]

BackgroundThe reasons for the high prevalence of depressive disorders in women of Pakistani origin living in the UK are not clear. The aim of this study was to determine the relative importance of life events, chronic social difficulties and acculturation in a population-based sample of British Pakistani women.MethodA cross-sectional and prospective cohort study of 18- to 65-year-old Pakistani women in UK was carried out. The Schedule for Clinical Assessment in Neuropsychiatry for diagnosis, the Life Events and Difficulties Schedule for social stress and an acculturation questionnaire were used.ResultsDepressive disorder at baseline was associated with older age, social isolation and marked difficulties involving health and close relationships. Depressive disorder at follow-up was associated with severity of depression at baseline, difficulties in close relationships and two aspects of acculturation, especially less acculturation in relation to use of the English language.ConclusionsLack of acculturation, especially less familiarity with the English language, is an independent predictor of persistence of depression in Pakistani women in UK. This needs to be taken into consideration when planning treatment, which also needs to address the personal difficulties associated with persistent depression. The implication of this work is that women of Pakistani origin with depression should be encouraged to receive help in the use of English as one part of treatment that may prevent relapse. [ABSTRACT FROM PUBLISHER]

Background Programmes that promote early psychological development of children in the developed world have been found to be beneficial. However, such programmes are rare in underprivileged parts of the developing world. We adapted one such parent-based programme (Learning Through Play) for a rural Pakistani population and aimed to study if: (1) it was acceptable to community health workers; (2) the programme led to an improvement, after a period of 6 months, in mothers' knowledge and attitudes about early infant development; (3) it led to a reduction in the levels of maternal mental distress in the post-natal period. Methods Using a cluster randomized design with villages as unit of randomization, 163 mothers from 24 villages in a rural sub-district of Rawalpindi, Pakistan, received the ‘Learning Through Play’ programme, whereas 146 mothers from 24 villages acted as controls. Twenty-four community health workers were trained to carry out the programme. Assessments were conducted using a specially developed 15-item Infant Development Questionnaire and the 20-item Self-Reporting Questionnaire (SRQ). Results Over 80% of the community health workers trained found the programme to be relevant and were able to integrate it into their routine work. There was a significant increase in mothers' knowledge and positive attitudes about infant development in the intervention group, compared with the control group. Women in the intervention group answered correctly 4.3 (95% CI 3.7–14.9, P < 0.001) more questions than the control group. There was no difference in levels of mental distress measured by the SRQ. Conclusions The ‘Learning Through Play’ programme was successfully integrated into the existing health system and accepted by community health workers. The programme succeeded in improving the knowledge and attitudes of mothers about infant development. [ABSTRACT FROM AUTHOR]

Previous studies have found no female predominance in irritable bowel syndrome (IBS) in non-Western countries. The aim of the study was to assess the prevalence and correlates of Rome II (IBS) in both sexes in Pakistan. A Population-based survey in a low-income inner city area using questionnaires to diagnose Rome II IBS and assess distress, disability and stressful life events. Data were collected from 880/938 (93%) randomly selected residents. 13.4% of women and 13.1% men met criteria for Rome II IBS; 34 (3.9%) had diarrhoea-predominant, 59 (6.7%) had constipation-predominant IBS and 24 (2.7%) had ‘mixed IBS’. In logistic regression analysis, IBS was associated in men with high income (OR = 1.56; 95% CI: 1.05–2.3) and few years of education (OR = 2.17; 95% CI: 1.2–3.9) and in women with being married (OR = 3.6; 95% CI: 1.1–11.9) and stressful life events score (OR = 1.14; 95% CI: 1.01–1.3). Disability was associated with constipation-predominant IBS (OR = 1.99; 95% CI: 1.1–3.6), distress (OR = 1.19; 95% CI: 1.14–1.23) and stressful life events (OR = 1.19; 95% CI: 1.1–1.3). Investigations were more likely in men (54%) than in women (27%) ( P = 0.003). These findings suggest that the equal sex ratio of IBS in urban Pakistan could result from a close association between marked distress and IBS in men similar to that found in women in western studies. [ABSTRACT FROM AUTHOR]

Background It is becoming well established that CBT is both effective and cost efficient in the treatment of positive and negative symptoms of schizophrenia. However, there is a need to adapt CBT to the cultural, linguistic, and socioeconomic context of diverse cultural groups. We aimed to establish the feasibility of culturally adaptive cognitive behavior therapy for treatment of psychosis in a low-income country. Methods This is a rater-blind, randomized, controlled trial of the use of CBT in patients with psychosis from a low-income country. Patients with a DSM-IV diagnosis of schizophreniform disorder were assessed using Positive and Negative Syndrome Scale for Schizophrenia (PANSS), PSYRATS (Psychotic Symptom Rating Scales), and the Insight Scale. Participants were randomized into the intervention group ( n = 18) and TAU group ( n = 18). The intervention group received 12 weekly sessions of culturally adapted CBT for psychosis (CaCBTp). Results There were no significant differences between the two groups at baseline. At three months follow-up, there was a statistically significant improvement in the CaCBTp group on PANSS general Psychopathology subscale, PANSS overall score and Insight scale, as compared to the TAU group. The CaCBTp group had lower scores on PANSS positive, PANSS negative sub-scales, and the two subscales of Psychotic Symptom Rating Scale, but differences were not statistically significant. Conclusion Culturally adapted CBT added to pharmacological treatment as usual was acceptable to patients and was helpful in reduction of severity of psychotic symptoms. Adjunctive culturally adapted CBT should be further investigated in this population. [ABSTRACT FROM AUTHOR]

Background: Depression is a global public health problem with highest rates in women in low income countries including Pakistan. There are no treatment trials from such countries comparing the efficacy of antidepressant treatment with a group psychological intervention. Methods: We conducted a preliminary RCT in an urban primary care clinic in Karachi, Pakistan. Consecutive eligible women scoring > 12 on the CIS-R and > 18 on HDRS (n=66) were randomly assigned to antidepressant or group psychosocial treatment. The primary outcome measure was HDRS score; secondary outcome measures were disability and quality of life. Results: 96% patients were assessed at 3 & 6 months after baseline. At 6 months response (50% reduction of HDRS score) occurred in 20 (60.6%) and 22(66.7%) of the psychosocial and antidepressant groups respectively. There was also significant reduction in disability and improvement in health related quality of life in both groups. Conclusion: Low costs antidepressants and group psychosocial treatment on the principles of CBT merit further assessment as primary treatments for depression in low income countries. [Copyright &y& Elsevier]

In high income countries depression is common among general trauma patients and is associated with a poor outcome. In the absence of previous reports from a developing country we evaluated the relationship of psychological distress to physical injury, musculoskeletal complaints, and social factors in Pakistan. Methods: One thousand and fourteen patients were recruited from a busy orthopaedic outpatient clinic at a general hospital in Karachi (90.5% response rate). Research assistants administered the Self Rating Questionnaire (SRQ) to measure psychological distress, the Oslo social support questionnaire, and the Brief Disability Questionnaire (BDQ). The surgeons documented the diagnosis and, if appropriate, rated symptoms as medically unexplained. Results: An SRQ score of 9 or more, which indicates probable depressive disorder, occurred in 45.6% of men & 76.1% of women. A high SRQ score was associated with female sex, divorced, separated or widowed status, little or no education, low income and little social support. Even after these were controlled for there was a significantly higher SRQ score in patients with arthritis, backache/prolapsed intervertebral disc, major fracture and other bone pathology. Overall there was no difference in SRQ score between patients with medically explained (by trauma or organic disease) or unexplained symptoms. Conclusions: Depressive disorder appears to be very common in orthopaedic out patients in this low income country and both social circumstances and nature of bone pathology are associated with such depression. Treatment should address this extreme psychological distress. [Copyright &y& Elsevier]

Introduction: Depression is a global public health problem with highest rates in women in low income countries including Pakistan. Paediatricians may be a resource to help with maternal depression. Little is known in low income countries about the prevalence of depression and its social correlates in mothers of children attending paediatric clinics. Methods: Using cross-sectional design consecutive women attending the paediatric clinic were screened using the Edinburgh Postnatal Depression Scale (n=185). Women scoring 12 or more (n=70) and a random sample of low scorers (n=16) were interviewed using the Clinical Interview Schedule Revised (CIS-R) to confirm the diagnosis of depression, the Oslo scale was used to measure social stress and EQ-5D for health related quality of life. Results: The prevalence of maternal depression was 51%. The mean age of the sample was 26 years. Depressed mothers were more likely to be living in a joint family household, they were less educated and they and their husbands were less likely to be employed. The depressed mothers had more financial difficulties and they were more likely to sleep hungry during the last month due to financial problems. The depressed mothers had less social support and poorer quality of life compared to non depressed mothers. Conclusion: Maternal depression in this health care setting is high and it is associated with social stress and poor social support. Paediatric appointments may be an opportunity for care and care delivery for maternal depression. [Copyright &y& Elsevier]

Background: Informed consent is considered to be the standard method for respecting the autonomy of individual participants in research and practices and is thought to be based on several conditions: (1) providing information on the purpose of the research or a specific treatment, what it will entail, (2) the participants being mentally competent to understand the information and weigh it in the balance, and (3) the participants to be free from coercion. While there are studies of informed consent in other countries, especially Low and Middle Income Countries (LMICs), this study explored the experiences of clinicians regarding the process of obtaining informed consent to participate in a Randomised Controlled Trial (RCT) in particular and treatment in general in healthcare settings, both general and mental health, specifically focusing on the tension between individualistic concept of autonomy and collectivist values in cultures such as Pakistan., Methods: Qualitative interviews with 20 clinicians from healthcare settings in Pakistan who also served as recruiters in a suicide prevention RCT in Pakistan. The interviews were guided by semi-structured topic guide. All interviews were audio-recorded and transcribed verbatim., Results: The interviews revealed that shared decision making was more morally important than individual autonomy, the role of the family played a dominant part in the consent-taking procedure, the decision of the elder and/or family patriarch took prominence, and that clinician-researchers encountered significant challenges in consent process in Pakistan, while recruiting patients into the trial as well as during routine treatment processes in healthcare settings. Four distinct themes emerged which were (1) Family deciding for patients, (2) Benefits of involving family in consent process, (3) Gender disparity in consent process, (4) Challenges experienced by clinician-researchers during consent process in Pakistan., Conclusions: The concept of consent is generally considered important in many cultures, however, there are two strands of understanding. There seems to be consensus that participant agreement is necessary to protect the participant but with regards to autonomy there are significant cultural differences whether it is the right for autonomy of the individual (individualistic concept) or family, community, or expert authority in other cultures. In Pakistan clinician-researchers sometimes preferred one approach and sometimes the other as they appreciated the interests of the patient to be., Competing Interests: Declarations Consent for publication Not Applicable. Competing interests IBC, NC, and NH have disclosed engagements encompassing presentations and consultancy roles with Eli Lilly, Bristol Myers Squibb, Lundbeck, AstraZeneca, and Janssen Pharmaceuticals. These interactions led to reimbursements for them or their respective employing institutions. NH and IBC have held positions as trustees at the PILL in the past. NH has also held roles as a trustee for organizations including Manchester Global Foundation, Lancashire Mind, and Abaseen Foundation, UK. Additionally, NH is an NIHR senior investigator and serves as the Director of Research and Innovation at Mersey Care NHS Foundation Trust. Importantly, none of the aforementioned companies maintain any financial stake in this research. RM is Director of Manchester Global Foundation and has also held trustee position at UK Association for Medical Aid to Pakistan (UKMAP) and PILL in the past. Ethics approval and informed consent to participate for the main study was obtained from the National Bioethics Committee of Pakistan (Ref: No.4–87/NBC419/19/1213) and the Research Ethics Committee University of Manchester (Ref: 2019-5024-10755). Ethics approval for RM’s thesis was granted by Science and Technology Department, University College London (Ref. STSEth159). All participants gave informed written consent to participate., (© 2024. The Author(s).)

Background: Variable benefits have been reported from the adjunctive use of simvastatin and the 5HT3 receptor antagonist, ondansetron, in patients with schizophrenia. We investigated their independent efficacy and possible synergy to improve negative symptoms of schizophrenia within a single trial., Methods: A 6-month, randomised, double-blind, placebo-controlled trial with a 4-arm, 2 × 2 factorial design, in three centres in Pakistan. In total, 303 people with stable treated schizophrenia aged 18-65 were randomly allocated to add-on ondansetron, simvastatin, both or neither. The primary outcome was a Positive and Negative Syndrome Scale (PANSS) negative score at 3 and 6 months., Results: Mixed model analysis and analysis of covariance revealed no main effects of simvastatin or ondansetron but a significant negative interaction between them ( p  = 0.03); when given alone, both drugs significantly reduced negative symptoms compared to placebo but they were ineffective in combination. Individual treatment effects versus placebo were -1.9 points (95%CIs -3.23, -0.49; p  = 0.01) for simvastatin and -1.6 points for ondansetron (95%CIs -3.00, -0.14; p  = 0.03). Combined treatment significantly increased depression and side effects. In those with less than the median 5 years of treatment, ondansetron improved all PANSS subscales, global functioning measures and verbal learning and fluency, whereas simvastatin did not., Conclusion: Small improvement in negative symptoms on simvastatin and ondansetron individually are not synergistic in combination in treating negative symptoms of schizophrenia. Ondansetron showed broad efficacy in patients on stable antipsychotic treatment within 5 years of illness. The findings suggest that ondansetron should be evaluated in patients at risk of psychosis or early in treatment., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: I.B.C. and N.H. have given lectures and advice to Eli Lilly, Bristol Myers Squibb, Lundbeck, Astra Zeneca and Janssen pharmaceuticals for which they or their employing institution have been reimbursed. M.I.H. has served as an advisor to MindSet Pharma, Psyched Therapeutics and Wake Network and reports grants from the Brain and Behavior Research Foundation, Canadian Institutes of Health Research, CAMH Foundation, Physician’s Services Incorporated Foundation and University of Toronto. M.I.H., I.B.C. and N.H. were previously trustees of the Pakistan Institute of Learning and Living. B.D. has share options in P1vital.com and is a PI on MRC grant MRC grant MR/S037675/1.

Background: Women's mental health during the perinatal period is a major public health problem in Pakistan. Many challenges and competing priorities prevent progress to address the large treatment gap. Aim To quantify the long-term impacts of untreated perinatal depression and anxiety in economic terms, thus highlighting its overall burden based on country-specific evidence., Methods: Cost estimates were generated for a hypothetical cohort of women giving birth in 2017, and their children. Women and children experiencing adverse events linked to perinatal mental health problems were modelled over 40 years. Costs assigned to adverse events included were those linked to losses in quantity and quality-of-life, productivity, and healthcare-related expenditure. Present values were derived using a discount rate of 3 %. Data were taken from published cohort studies, as well as from sources of population, economic and health indicators., Results: The total costs were $16.5 billion for the cohort and $2680 per woman giving birth. The by far largest proportion referred to quality-of-life losses ($15.8 billion). Productivity losses and out-of-pocket expenditure made up only a small proportion of the costs, due to low wages and market prices. When the costs of maternal suicide were included, total costs increased to $16.6 billion., Limitations: Important evidence gaps prevented the inclusion of all cost consequences linked to perinatal mental health problems., Conclusions: Total national costs are much higher compared with those in other, higher middle-income countries, reflecting the excessive disease burden. This study is an important first step to inform resource allocations., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Elevated risk of psychosis for ethnic minority groups has generally been shown to be mitigated by high ethnic density. However, past survey studies examining UK Pakistani populations have shown an absence of protective ethnic density effects, which is not observed in other South Asian groups., Aims: To assess the ethnic density effect at a local neighbourhood level, in the UK Pakistani population in East Lancashire., Method: Data was collected by the East Lancashire Early Intervention Service, identifying all cases of first episode psychosis (FEP) within their catchment area between 2012 and 2020. Multilevel Poisson regression analyses were used to compare incidence rates between Pakistani and White majority groups, while controlling for age, gender and area-level deprivation. The ethnic density effect was also examined by comparing incidence rates across high and low density areas., Results: A total of 455 cases of FEP (364 White, 91 Pakistani) were identified. The Pakistani group had a higher incidence of FEP compared to the White majority population. A clear effect of ethnic density on rates of FEP was shown, with those in low density areas having higher incidence rates compared to the White majority, whereas incidence rates in high density areas did not significantly differ. Within the Pakistani group, a dose-response effect was also observed, with risk of FEP increasing incrementally as ethnic density decreased., Conclusions: Higher ethnic density related to lower risk of FEP within the Pakistani population in East Lancashire, highlighting the impact of local social context on psychosis incidence.

Purpose: The global burden of mental health difficulties among children underscores the importance of early prevention. This study aims to assess the efficacy, feasibility and acceptability of the Strong Families programme in enhancing child behaviour and family functioning in low-resource settings in Gilgit-Baltistan, Pakistan., Methods and Analysis: This is a two-arm, multisite feasibility randomised controlled trial with an embedded process evaluation in three districts of Gilgit-Baltistan, namely Gilgit, Hunza and Skardu. 90 families living in these challenged settings, comprising a female primary caregiver aged 18 or above, and at least one child aged 8-15 years, will participate. Participants will be randomly assigned to either receive the Strong Families programme or to the waitlist group. Strong Families is a 7-hour family skills group intervention programme attended by children and their primary caregivers over 3 weeks. The waitlist group will be offered the intervention after their outcome assessment. Three raters will conduct blind assessments at baseline, 2 and 6 weeks postintervention. The primary outcome measures include the feasibility of Strong Families, as determined by families' recruitment and attendance rates, and programme completeness (mean number of sessions attended, attrition rates). The secondary outcomes include assessment of child behaviour, parenting practices, parental adjustment and child resilience. Purposefully selected participants, including up to five caregivers from each site, researchers and facilitators delivering the intervention, will be interviewed. Descriptive statistics will be used to analyse primary and secondary outcomes. The process evaluation will be conducted in terms of programme context, reach, fidelity, dose delivered and received, implementation, and recruitment., Ethics and Dissemination: This study has been approved by the UNODC Drug Prevention and Health Branch in the Headquarters office of Vienna and the National Bioethics Committee of Pakistan. Findings will be disseminated through publication in reputable journals, newsletters and presentations at conferences., Trial Registration Number: NCT05933850., Competing Interests: Competing interests: IBC, NC and NH have disclosed engagements encompassing presentations and consultancy roles with Eli Lilly, Bristol Myers Squibb, Lundbeck, AstraZeneca and Janssen Pharmaceuticals. These interactions led to reimbursements for them or their respective employing institutions. NH and IBC have held positions as trustees at the PILL in the past. NH has also held roles as a trustee for organisations including Manchester Global Foundation, Lancashire Mind and Abaseen Foundation, UK. Additionally, NH is an NIHR senior investigator and serves as the Director of Research and Innovation at Mersey Care NHS Foundation Trust. Importantly, none of the aforementioned companies maintains any financial stake in this research., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Clinical equipoise, also defined as the uncertainty principle, is considered essential when recruiting subjects to a clinical trial. However, equipoise is threatened when clinicians are influenced by their own preferences. Little research has investigated equipoise in the context of trial recruitment., Methods: This cross-sectional survey sought clinicians' views (operationalised as 11 statements relating to treatments offered in a trial of a psychological intervention for young people) about equipoise and individual treatment preferences in the context of moral justification for recruiting young people at risk of self-harm or suicide to a randomised controlled trial (RCT) to evaluate the Youth Culturally Adapted Manual Assisted Psychological Intervention (Y-CMAP) in Pakistan. We compared the views of clinicians involved in Y-CMAP RCT recruitment to those of a sample of clinicians not involved in trial recruitment but treating similar patients, comparing their sociodemographic characteristics and the proportions of those in each group agreeing with each statement., Results: There was a response rate of 96% (75/78). Findings showed that, during trial recruitment and before the RCT results were known, the majority of all responding clinicians (73.3%) considered Y-CMAP to be an effective treatment for young people at risk of self-harm or suicide. Although there was an acknowledgement of individual preferences for the intervention, there was near consensus (90%) on the need to conduct an RCT for reaching an evidence-based decision. However, there were no significant differences in the proportion of recruiting clinicians reporting a treatment preference for Y-CMAP than non-recruiting clinicians (31 (88.6%) versus 36 (90%), p = 0.566). A significantly higher proportion of non-recruiting clinicians (87.5%) as compared to (48.5%) in the trial (p = 0.000) stated that there may be other treatments that may be equally good for the patients, seemingly undermining a preference for the intervention. Those reporting a treatment preference also acknowledged that there was nothing on which this preference was based, however confident they felt about them, thus accepting clinical equipoise as ethical justification for conducting the RCT. There was a significant group difference in views that treatment overall is better as a result of young patients' participation in the Y-CMAP trial (p = 0.015) (i.e. more clinicians not involved in the trial agreed with this statement). Similarly, more clinicians not involved in the trial agreed on the perceived availability of other treatment options that were good for young people at risk of self-harm (p < 0.05)., Conclusions: The paper highlights that clinicians in Pakistan accept the notion of clinical equipoise as an ethical justification for patient participation in RCTs. The need for conducting RCTs to generate evidence base and to reduce bias was considered important by the clinical community., (© 2023. BioMed Central Ltd., part of Springer Nature.)

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., Competing Interests: Competing interests: NH, former Trustee of 'Pakistan Institute of Living and Learning (PILL)', 'Abaseen Foundation (UK)' and 'Lancashire Mind (UK)'. At 'Manchester Global Foundation', he is the Chair of Board of Trustees. He is also a member of the executive committee for the Faculty of Academic Psychiatry, at the Royal College of Psychiatrists. NH is a NIHR Senior Investigator. NC is Associate Director of Global Mental Health and Cultural Psychiatry Research Group. IBC, former Trustee of 'PILL' is Honorary Professor at the University of Manchester. NH, IBC and NC have received support for educational programmes and/or travel support and/or speaker fees from pharmaceutical companies. CW is the author of a book aimed at suicide prevention, and has written a range of books and online CBT-based course resources that are available as both, free access and on a commercial basis. NH, NC, IBC and TK’s time is partially funded by the Global Challenges Research Fund 'South Asia Harm Reduction Movement-SAHAR M' (MR/P028144/1)., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

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., (Copyright © 2021. Published by Elsevier Inc.)

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.

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.

Background: Associations between childhood trauma, personality, and Major Depressive Disorder (MDD) have been well established in studies conducted in high-income countries. However, there are limited studies on these associations in low and middle-income countries (LMICs), where MDD is highly prevalent. We assessed the relationships between childhood trauma, personality, and MDD in women in Karachi, Pakistan., Method: In this cross-sectional study of 455 female patients attending general medical outpatient clinics, a diagnosis of MDD was confirmed using the Structured Clinical Interview for DSM-IV (SCID); retrospective reports of childhood trauma were collected using the childhood trauma questionnaire (CTQ); and Big Five personality traits were assessed using the NEO Personality Inventory Revised (NEO PI-R). Other measures included the Life Events Questionnaire (LEQ) and the Multidimensional Scale of Perceived Social Support (MSPSS). Factors independently associated with MDD were determined using logistic regression analyses., Results: Of the 455 women recruited between August 1, 2011 and July 31, 2013, 242 (53%) had a diagnosis of MDD. Women with MDD were significantly more likely to be separated, had more stressful life events and higher CTQ scores. Higher perceived social support, conscientiousness and extraversion were independently associated with significantly reduced odds of MDD. There were no significant associations between CTQ scores and any of the NEO PI-R subscales., Limitations: Ratings of childhood trauma were based on retrospective recall., Conclusion: MDD and a history of childhood trauma were highly prevalent in Pakistani women attending general medical clinics. Interventions to prevent childhood trauma and promote social support in women may improve public mental health in LMICs like Pakistan., (Copyright © 2021. Published by Elsevier B.V.)

The prevalence and risk factors of suicidal ideation in bipolar depression in low- and middle-income countries (LMICs) are poorly understood. This study is a secondary, cross-sectional analysis of a randomized controlled trial from Pakistan, a lower middle-income country. Participants included psychiatric outpatients aged 18 to 65 with a known diagnosis of bipolar disorder and currently in a depressive episode. Suicidality was assessed using the suicide item of the 17-item Hamilton Depression Rating Scale (HAM-D) and levels of severity were categorized as absent, mild/moderate, or severe. Biometric data and biomarkers were obtained. Descriptive statistics were used to describe prevalence and logistic regression applied to establish correlates to suicidal ideation. Among the 266 participants, 67% indicated suicidality of any level and 16% endorsed severe suicidality. Lower body mass index (BMI) (OR = 0.93, 95% CI = 0.88-0.98), higher HAM-D score (OR = 1.29, 95% CI = 1.16-1.43), lower C-reactive protein (CRP) level (OR = 0.53, 95% CI = 0.40-0.70), and increased number of inpatient hospitalizations (OR = 1.16, 95% CI = 1.03-1.31) were identified as significant predictors of suicidality in the fully adjusted regression model. Our findings add to the limited literature on suicidality in bipolar disorder in the LMIC context and suggest roles of biological variables such as BMI and CRP level in predicting suicidal ideation and potentially suicidal behaviours in bipolar depression., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Suicide is a serious global public health problem and the third leading cause of death in those 15-35 years old. Self-harm is the major predictor of future suicide attempts and completed suicide yet remains poorly understood. There is limited evidence on effective interventions for adolescents who present with self-harm. To identify and develop acceptable preventive and therapeutic interventions it is essential to understand the factors that contribute to self-harm and suicide in young people, in the context of their emotions, interpersonal difficulties, available support and prevention strategies. This qualitative study aimed at exploring the lived experiences of adolescents presenting with self-harm and their views about potential prevention strategies. Semi-structured interviews with 16 adolescents (12-18 years) presenting with a self-harm episode in a public hospital in Pakistan. A topic guide was developed to facilitate the interviews. The following themes emerged using the framework analysis; predisposing factors (interpersonal conflicts, emotional crisis etc.), regret and realization that self-harm is not the only option, perceived impact of self-harm, and suggestions for suicide prevention strategies (sharing, distraction techniques, involvement of family). This study may help in refining a contextual and culturally based explanatory model of self-harm in adolescents and in informing development of culturally acceptable interventions.

Efforts to build research capacity and capability in low and middle income countries (LMIC) has progressed over the last three decades, yet it confronts many challenges including issues with communicating or even negotiating across different cultures. Implementing global research requires a broader understanding of community engagement and participatory research approaches. There is a considerable amount of guidance available on community engagement in clinical trials, especially for studies for HIV/AIDS, even culturally specific codes for recruiting vulnerable populations such as the San or Maori people. However, the same cannot be said for implementing research in global health. In an effort to build on this work, the Pakistan Institute of Living and Learning and University College London in the UK sought to better understand differences in beliefs, values and norms of local communities in Pakistan. In particular, they have sought to help researchers from high income countries (HIC) understand how their values are perceived and understood by the local indigenous researchers in Pakistan. To achieve this end, a group discussion was organised with indigenous researchers at Pakistan Institute of Living and Learning. The discussion will ultimately help inform the development of a cultural protocol for researchers from HIC engaging with communities in LMIC. This discussion revealed five common themes; (1) religious principles and rules, (2) differing concepts of and moral emphasis on autonomy and privacy, (3) importance of respect and trust; (4) cultural differences (etiquette); (5) custom and tradition (gift giving and hospitality). Based on the above themes, we present a preliminary cultural analysis to raise awareness and to prepare researchers from HIC conducting cross cultural research in Pakistan. This is likely to be particularly relevant in collectivistic cultures where social interconnectedness, family and community is valued above individual autonomy and the self is not considered central to moral thinking. In certain cultures, HIC ideas of individual autonomy, the notion of informed consent may be regarded as a collective family decision. In addition, there may still be acceptance of traditional professional roles such as 'doctor knows best', while respect and privacy may have very different meanings.

Background: The risk factors and adverse outcomes related to maternal depression and child malnutrition are a leading cause of morbidity and mortality in low and middle-income countries (LMIC) including Pakistan. Above 25% of women suffer from maternal depression. Up to 50% children are under-nourished which contributes to 35% of all under-5 deaths in the country., Aim: To determine the efficacy of Learning through Play Plus Thinking Healthy Program (LTP Plus) intervention to reduce maternal depression in mothers with undernourished children., Methods: In this randomised controlled trial, all eligible mothers presenting to the paediatric departments were invited to participate in the study. Out of the total 256 mothers screened, 107 were included, 54 of those were randomly allocated to LTP Plus group and 53 to treatment as usual (TAU). Edinburgh Postnatal Depression Scale (EPDS) was used to screen for depression. Hamilton Depression Rating Scale (HDRS), Maternal Attachment Inventory (MAI), Social Support Scale (OSLO-3) and the Euro-QoL (EQ-5D) were used to measure the severity of depression, mother-child attachment, level of support and health related quality of life dimensions. Assessments were completed at baseline, end of intervention (3 months from baseline) and at 6 months from baseline., Results: Mothers in the LTP Plus group significantly showed improvements in depression (p<0.001), social support (p = 0.02) and quality of life (p<0.001) at the end of the intervention (LTP Plus), as compared to the TAU group, which were sustained up to 6 months after baseline., Conclusion: The outcomes of LTP Plus intervention for mothers of malnourished children show promising results in reducing maternal depression and improving child outcomes. A full trial with longer-term outcomes and cost-effectiveness needs to be conducted., (Copyright © 2020. Published by Elsevier B.V.)

Background: Several small studies suggest that the adjunctive use of anti-inflammatory agents might improve depressive symptoms in bipolar disorder. However, there are few well designed, appropriately powered clinical trials assessing the efficacy of these novel treatment strategies. We aimed to assess the efficacy of adjunctive minocycline or celecoxib in this setting., Methods: This double-blind, 12-week, randomised, placebo-controlled trial was done in four outpatient psychiatric clinics in Pakistan. Eligible participants were adults (aged 18-65 years) with DSM-5 bipolar disorder (type I or II) and a major depressive episode. In a 2 × 2 factorial design, participants were randomly assigned (1:1:1:1) to receive either active minocycline plus active celecoxib, active minocycline plus placebo celecoxib, placebo minocycline plus active celecoxib, or placebo minocycline plus placebo celecoxib. The primary outcome was the mean change from baseline to week 12 in score on the 17-item Hamilton Depression Rating Scale (HAMD-17), assessed in all randomised participants (missing data were imputed and assumed to be missing at random). The trial was registered with ClinicalTrials.gov, NCT02703363., Findings: 266 (17%) of 1542 patients assessed between May 1, 2016, and March 31, 2019, were randomly assigned to receive minocycline plus celecoxib (n=68), minocycline plus placebo (n=66), celecoxib plus placebo (n=66), or placebo plus placebo (n=66). From baseline to week 12, depressive symptoms as per HAMD-17 reduced in all four groups (from 24·5-25·2 to 11·3-12·8), but these reductions did not differ significantly between the groups. In terms of main effects, reductions in HAMD-17 did not differ for patients treated with minocycline (mean adjusted difference vs non-minocycline 1·48 [95% CI -0·41 to 3·36]; p=0·123) or for celecoxib (mean adjusted difference vs non-celecoxib -0·74 [-2·61 to 1·14]; p=0·443). Rates of serious adverse effects did not differ between groups (31 participants had a manic switch, two self-harmed, and one died in a motor vehicle accident)., Interpretation: We found no evidence that minocycline or celecoxib was superior to placebo for the treatment of bipolar depression. This large trial casts doubt on the potential therapeutic benefits of adjunctive anti-inflammatory drugs for the acute management of bipolar depression., Funding: Stanley Medical Research Institute., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Self-harm is a major public health issue in Pakistan, yet the characteristics of those who self-harm are under-explored. This is a secondary analysis from a large randomized control trial on the prevention of self-harm, exploring demographic, clinical and psychological characteristics of people who self-harm in Pakistan. A total of 221 participants with a history of self-harm were recruited from medical wards of three major hospitals in Karachi. The Beck Scale for Suicidal Ideation (BSI), Beck Depression Inventory (BDI), Beck Hopelessness Scale (BHS), and Suicide Attempt Self Injury Interview (SASII) assessment scales were completed. The sample consisted predominantly of females (68.8%) in their 20's. Interpersonal difficulties were most commonly reported as the main antecedent to the self-harm, followed by financial difficulties. Participants had high severity scores on BSI, BDI and BHS. Pesticide and insecticide use were (n = 167, 75.6%) the most common methods of self-harm. The findings indicate that some characteristics of those who self-harm in Pakistan are comparable to other populations. This may raise the possibility of common causal mechanisms and processes. Future research needs to examine the efficacy of interventions targeting these risk factors in reducing rates of self-harm and thus suicide., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: Evidence demonstrates the detrimental impact of depression in patients with congestive heart failure (CHF), however, large-scale prospective data from Low and Middle Income Countries (LMICs) is limited. We assessed the prevalence of depression in a large sample with CHF from Karachi, Pakistan, and the impact of depression on all-cause mortality, disability and health-related quality of life (QoL)., Methods: 1009 patients diagnosed with CHF were recruited from public hospitals in Karachi, Pakistan. Patients were screened for depression at baseline using the Beck Depression Inventory (BDI) and the diagnosis was confirmed using the Clinical Interview Schedule-Revised (CIS-R). Health-related QoL and disability were measured using the EuroQol (EQ-5D) and Brief Disability Questionnaire respectively at baseline and after a 6-month follow-up., Results: A total of 670 (66%) patients were depressed at baseline and 821 participants completed 6-month follow up assessments (retention rate: 81%). At baseline, lower income (p < 0.001) and lower education level (p = 0.03) were associated with higher BDI scores. Higher BDI scores were associated with a history of depression (p < 0.001), higher NYHA class (p < 0.001), diabetes (p < 0.001), COPD (p = 0.007), renal disease (p < 0.001) and stroke (p = 0.02). 145 participants were deceased at 6-months. Regression analysis showed that at follow up, higher BDI scores in depressed participants were associated with higher all-cause mortality (OR 1.23 (95% CI: 1.11-1.36); p < 0.001)., Conclusion: The rate of depression was high among Pakistani patients with CHF. Severity of depression correlated with increased mortality. Further research on controlled intervention trials in this population is warranted., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: British Pakistanis are one of the largest ethnic minority groups living in the UK, with high rates of maternal depression being reported in this population. Evidence suggests that culturally-adapted Cognitive Behavioural Therapy (CBT)-based interventions for depression, may improve clinical outcomes and patient satisfaction. This study was conducted to develop and test the feasibility and acceptability of a culturally-adapted, CBT-based, manual-assisted intervention in British Pakistani mothers experiencing maternal depression., Methods: A mixed-method feasibility study that included qualitative interviews followed by the development of a CBT-based intervention for mothers with mild to moderate depression. Following the qualitative interviews, a CBT-based intervention called the Positive Health Program (PHP) was developed and delivered consisting of 12-weekly sessions. A before and after design was used to explore the feasibility and acceptability of the Positive Health Programme., Results: A culturally-adapted CBT-based group intervention (PHP) was acceptable to this group and improvements were reported in depression and health-related quality of life. The women's understanding of 'depression' as a general consensus was in physical terms, but with an onset triggered by psychosocial causes. The most commonly reported factors contributing to depression were marital disharmony, lack of social support, and financial difficulties. Past help offered was primarily antidepressants, which were not welcomed by most of the women. A lack of availability of culturally sensitive interventions and the limited cultural sensitivity of NHS staff was also reported., Conclusion: This study provides preliminary evidence for the feasibility and acceptability of a CBT-based culturally-adapted group psychological intervention for British Pakistani mothers., Trial Registration: Study ethics registration number: 10/H1005/62 (University of Manchester).

Background: The incidence of depression is difficult to determine because of low clinical depression detection rates in the primary care setting. This low level of detection is a significantly greater problem in people from ethnic minority communities. The availability of culturally validated screening questionnaires might help to improve the detection and treatment of depression., Method: The aim of the study was to assess the validity of the self-reporting questionnaire SRQ 20, (English and Urdu versions) in white Europeans and British Pakistanis and to determine the optimum cut-off scores for detecting depression. Validation of the English and Urdu versions of the SRQ was conducted with a sample of white Europeans and British Pakistani participants. The semi-structured Schedule for Clinical Assessment in Neuropsychiatry (SCAN) was used as the gold standard diagnostic interview, and receiver operating characteristic analysis was used to evaluate SRQ test performance., Results: The SRQ was completed by 1856 participants out of whom 651 completed the SCAN interview. The SRQ sensitivity, specificity, and predictive values versus SCAN indicated a cut-off score of 7 as optimum for white Europeans and a cut-off score of 6 for British Pakistanis., Limitations: This study focused on depression alone and did not take into consideration comorbid conditions such as anxiety which might have affected the way respondents answered the questions and contributed to comparatively lower optimum cut-off scores in British Pakistanis., Conclusions: The findings of this validation study provide evidence for high sensitivity and specificity of SRQ amongst both white Europeans and British Pakistanis. The SRQ can be used as a routine screening questionnaire for depression in English and Urdu speaking populations in the UK., (Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.)

Background: Depression is one of the leading causes of disability worldwide. A high proportion of patients do not respond to standard drug treatments. Recent evidence has suggested that anti-inflammatory treatment may have beneficial effects in major depression. Minocycline is a tetracycline antibiotic with good CNS penetration that exerts effects on multiple interacting symptoms implicated in the pathophysiology of mood disorders. Open-label studies have suggested that minocycline is effective as an adjunct drug in improving depressive symptoms., Methods/design: This is a multi-centre, 3-month, double-blind, placebo-controlled, pilot trial of minocycline added to treatment as usual for patients suffering from DSM-IV major depressive disorder. This will be a double-blind, randomised, controlled, two parallel-arm study with 20 participants in each arm, giving a total of 40 participants. There will be a screening visit, a randomization visit and four follow-up visits. Clinical assessments using the Hamilton Depression Rating Scale (HAM-D), Clinical Global Impression scale (CGI), Patient Health Questionnaire-9 (PHQ -9) and the Generalised Anxiety Disorder scale (GAD-7) will be carried out at every visit. Side effects checklists will also be undertaken at each visit. Biomarkers (inflammatory cytokines and CRP) will be measured at baseline and at the end of the treatment phase. Minocycline will be started at 100 mg once daily (OD) and will be increased to 200 mg at two weeks., Discussion: Anti-inflammatory treatments have been shown to have some beneficial effects in the treatment of major depressive disorder. The aim of this pilot randomised controlled trial is to establish the degree of improvement in depressive symptoms with the addition of minocycline to treatment as usual., Trial Registration: ClinicalTrials.gov NCT02263872 registered 10 October 2014.

Background: Methotrexate is a commonly used anti-inflammatory and immunosuppressive drug. There is growing evidence that inflammatory processes are involved in the pathogenesis of schizophrenia. In our recent randomised double-blind placebo-controlled clinical trial in Pakistan and Brazil, the addition of minocycline (antibiotic and anti-inflammatory drug) for 1 year to treatment as usual reduced negative symptoms and improved some cognitive measures. A meta-analysis of cytokine changes in the peripheral blood has identified IL-2, IFN-gamma, TNF-alpha and soluble IL-2 receptor as trait markers of schizophrenia because their levels were elevated during acute exacerbations and reduced in remission. This suggests immune activation and an inflammatory syndrome in schizophrenia. Based on the evidence of the strong anti-inflammatory properties of methotrexate, we propose that low-dose methotrexate may be an effective therapy in early schizophrenia., Methods/design: This is a double-blind placebo-controlled study of methotrexate added to treatment as usual for patients suffering from schizophrenia, schizoaffective disorder, psychosis not otherwise specified or schizophreniform disorder. This will be with 72 patients, 36 in each arm over 3 months. There will be screening, randomisation and follow-up visits. Full clinical assessments will be carried out at baseline, 2, 4, 8 and 12 weeks. Social and cognitive assessments will be carried out at baseline and 12 weeks. Methotrexate will be given at a dose of 10 mgs orally once a week for a 3-month period., Discussion: Evidence suggests inflammatory processes are involved in the pathogenesis of schizophrenia and anti-inflammatory treatments have shown to have some beneficial effects. Methotrexate is a known immunosuppressant and anti-inflammatory drug. The aim of this study is to establish the degree of improvement in positive and negative symptoms, as well as cognitive functioning with the addition of methotrexate to treatment as usual.ClinicalTrials.gov identifier: NCT02074319 (24 February 2014).

Objective: To examine the psychosocial correlates and association of psychological distress and quality of life (QOL) in patients with medically unexplained symptoms (MUS) compared to those with medically explained symptoms (MES) in a primary care setting in Karachi, Pakistan., Methods: A cross-sectional study of 472 patients attending GP clinics between March and August 2009 in Karachi. Participants completed questionnaires to assess demographic details, somatic symptoms, anxiety, depression, and QOL. The patients' GP recorded whether the presenting complaint was medically unexplained or medically explained., Results: MUS subjects in our study were more educated, had better social support and fewer financial problems, were less depressed and had a better QOL than subjects who had medically explained symptoms (non-MUS). Both groups (MUS and non-MUS) were comparable in terms of anxiety and number of somatic symptoms, but non-MUS subjects were more depressed than the MUS group. In a regression analysis, the number of somatic symptoms and lower levels of anxiety predicted poorer QOL in this sample. Whether these symptoms were medically explained (or not) did not seem to contribute significantly to the QOL., Conclusion: Our findings confirm that even in the developing world, patients with MUS are common among primary care attendees. However, patients with MUS in urban Karachi, Pakistan may differ from Western MUS subjects in the role of stress, support, and anxiety in their presentation, and may be reflective of a conceptually different group of difficulties., (© 2015, The Author(s).)

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.

Background: Negative symptoms and cognitive deficits are two partially-related features of schizophrenia which have a major negative impact on social function and objective quality of life. Standard drug treatments have little impact on either. There is some evidence that anti-inflammatory treatment may have beneficial effects in schizophrenia and major depression. Statins are cholesterol-lowering agents that have been found to be anti-inflammatory agents and are also known to decrease C-reactive protein (CRP). Ondansetron is a serotonin (5-HT3) receptor antagonist widely used to prevent nausea and vomiting in patients receiving chemotherapy for cancer. Small studies have suggested that ondansetron is effective as an adjunct drug in improving the symptoms of schizophrenia., Methods/design: This is a two center, six-month, double-blind placebo controlled, factorial design study of ondansetron and/or simvastatin added to treatment as usual for patients suffering from schizophrenia, schizoaffective disorder, psychosis not otherwise specified or schizophreniform disorder. This will be a 2 × 2 design, with 54 patients in each cell, giving a total of 216 patients over three years. There will be a screening, a randomization and seven follow-up visits. Full clinical and neurocognitive assessments will be carried out at baseline (randomization), 14 weeks and at 26 weeks, while the positive and negative syndrome scale (PANSS), pill count and side effects checklist will be carried out at every visit. Simvastatin will be started at 20 mg once daily (OD), this will be increased to 40 mg after four weeks. Ondansetron will be administered in an 8 mg dose., Discussion: Anti-inflammatory treatments have been shown to have some beneficial effects in schizophrenia. Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared to treatment as usual. The aim of this study is to establish the degree of improvement in negative symptoms with the addition of ondansetron and/or simvastatin to treatment as usual., Trial Registration: [corrected] ClinicalTrials.gov NCT01602029.

Background: Depressive disorders are common and disabling among perinatal women. The rates are high in ethnic minority groups. The causes are not known in British Pakistani women. The aim of this study was to estimate the rates, correlates and maintaining factors of perinatal depression in a Pakistani sample in UK. The design used was a cross-sectional two phase population based survey with a prospective cohort study., Methods: All women in 3rd trimester attending antenatal clinic were screened with the Edinburgh postnatal depression scale (EPDS). Women scoring 12 or more on EPDS and a random sample of low scorers were interviewed using the Schedules for Assessment in Neuropsychiatry (SCAN) and the Life Events and Difficulties schedule (LEDS). Social support was assessed with the Multidimensional Scale for Perceived Social Support (MSPSS). They were reassessed 6 months after the delivery using the same measures., Results: The weighted prevalence of depression was 16.8%. Depressed mothers had more marked non health difficulties (housing, financial and marital). They had less social support and were socially isolated. Marked social isolation and marked non-health related difficulties were independent predictors of depression. Analyses of all the possible risk factors, comparing 26 persistent depressed with 27 depression resolved group showed significant differences in the MSPSS subscales between the two groups., Limitations: The study lacked inter-rater reliability testing between the individuals carrying out diagnostic interviews. The study sample did not accurately represent the general population and information about the origins of depression in this group of mothers was limited., Conclusion: Depression in British Pakistani mothers is associated with social isolation, poor social support and severe and persistent social difficulties. The findings will have implications in planning suitable services for this group., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The onset and early course of schizophrenia is associated with subtle loss of grey matter which may be responsible for the evolution and persistence of symptoms such as apathy, emotional blunting, and social withdrawal. Such 'negative' symptoms are unaffected by current antipsychotic therapies. There is evidence that the antibiotic minocycline has neuroprotective properties. We investigated whether the addition of minocycline to treatment as usual (TAU) for 1 year in early psychosis would reduce negative symptoms compared with placebo. In total, 144 participants within 5 years of first onset in Brazil and Pakistan were randomised to receive TAU plus placebo or minocycline. The primary outcome measures were the negative and positive syndrome ratings using the Positive and Negative Syndrome Scale. Some 94 patients completed the trial. The mean improvement in negative symptoms for the minocycline group was 9.2 and in the placebo group 4.7, an adjusted difference of 3.53 (s.e. 1.01) 95% CI: 1.55, 5.51; p < 0.001 in the intention-to-treat population. The effect was present in both countries. The addition of minocycline to TAU early in the course of schizophrenia predominantly improves negative symptoms. Whether this is mediated by neuroprotective, anti-inflammatory or others actions is under investigation.

Objective: To study cardiotoxicities, especially bradycardia in cancer patients treated with 5-Fluouracil and 5-Fluouracil based chemotherapy regimens in Pakistani population., Methods: Data was extracted from the medical records of all diagnosed cancer patients at Shaukat Khanum Memorial Cancer Hospital and Research Center registered between January 2002 and December 2004 receiving 5- Fluouracil based chemotherapy regimens. The data was analysed retrospectively, including electrocardiogram and cardiac markers. Pearson's Correlation coefficient was calculated to see any possible correlation between 5-Fluouracil alone and 5-Fluouracil based regimens and cardiotoxicity, and other variables., Results: Symptomatic cardiotoxicity was observed in 60 (19.93%) out of 301 patients whose cases were part of the study. Bradycardia was the most common cardiotoxicity and was observed in 36 (11.96%) patients. Nine (2.99%) mortalities were also observed. The incidence of cardiotoxicity was not significantly different between the patients with and without pre-existing cardiovascular disease (p = 0.095) and having negative correlation - 0.305. Cardiotoxicities were more common with Continuous Infusion (CI) of 5-Fluouracil, radiotherapy concurrent with 5-Fluouracil and when 5-Fluouracil was used in combination with Cisplatinum (CDDP)., Conclusion: Cardiotoxicities were more prevalent when 5-Fluouracil was used along with concurrent radiotherapy and with Cisplatinum and when administered in continuous infusion pattern. Hence, 5-Fluouracil and 5-Fluouracil based chemotherapy regimens cause cardiotoxicities, especially bradycardia, in a significant number of cancer patients in Pakistani population.

Depression around childbirth is common in low income countries. The aim of this study was to examine the factors associated with persistence of depression from the antenatal to the postnatal period in urban Pakistan. A total of 1,357 pregnant women in their third trimester attending the antenatal clinic were included in the study. From these, 763 mothers who delivered at the study maternity home were reassessed after 3 months of childbirth. Edinburgh Postnatal Depression Scale (EPDS) was administered to measure depression in both the antenatal and the postnatal periods. Psychological distress, disability and life events experienced by mothers were also measured by using the Self-Reporting Questionnaire (SRQ-20), Brief Disability Questionnaire (BDQ), and Life Events Checklist, respectively. We found 25.8% prevalence rate of antenatal depression and 38.3% persistent depression in a private clinic. Persistently depressed mothers had significantly high psychological distress, more disability, and experienced more stressful life events than the resolved group. Our findings confirm the high rates of depression during pregnancy but we found low rates of persistent depression in this urban population as compared to the previous report. There is a need for further investigation of factors associated with persistent depression in order to develop appropriate interventions.

Objective: To determine the prescribing preference of mental health professionals in a developing country for antidepressants if they themselves developed a depressive illness., Methods: A specifically designed self reporting questionnaire was used to investigate which antidepressant was the preferred choice of psychiatrists and nurses and the factors which influenced their decision making., Results: Fluoxetine was the antidepressant most likely to be chosen by psychiatrists for themselves, followed by escitalopram and tricyclic antidepressant. A total of 21 (27.6%) nurses said that they did not know which antidepressant they would prefer for themselves and 22 (29%) said that they would choose a benzodiazepine. Majority of the psychiatrists (71.9%) had more experience with SSRIs, 26.6% with tricyclic antidepressants and only about 1.5% had used venlafaxine and mirtazapine. Efficacy and safety of antidepressants were the two most important factors in selecting an antidepressant., Conclusions: SSRIs are the preferred antidepressants of Pakistani psychiatrists and nurses for their patients and for themselves. Efficacy and safety of a drug are likely to play a greater role in drug choice than cost of the drug.

Objectives: In this study, we explored the attitudes toward Medically Unexplained Symptoms (MUS) of 500 general practitioners (GPs) in Karachi, Pakistan. Using a questionnaire previously developed by Reid et al. (2001), we aimed to investigate whether GPs' attitudes toward medically unexplained symptoms are similar to those of GPs in the developed world., Methods: Five hundred GPs on the database of primary care centers at the Pakistan Institute of Learning and Living in Karachi were all sent a covering letter explaining the purpose of the survey with a case vignette, a questionnaire, and a stamped addressed envelope. One month later, non-respondents received a telephone call from an investigator to remind them of the study., Results: Of the 429 respondents, 68.5% (294) were male and 31.5% (135) female. Although 80.2% of respondents felt that the main role of GPs was to provide support and reassurance, 76.9% of respondents also agreed that GPs had a role in referring patients with MUS for further investigations to identify a cause. Two hundred and four (47.55%) respondents agreed that somatization was useful concept, only 146 (34.03%) felt that there was effective treatment for it., Conclusion: For the most part, Pakistani GPs' attitudes toward MUS are not very different to those of their counterparts in the West. Both agree that the GP has an important role in providing reassurance and counseling. However, our survey also shows that Pakistani GPs are less likely to place emphasis on an underlying psychiatric diagnosis and tend to focus on looking for an underlying physical cause.

Background: British Pakistani women have a high prevalence of depression. There are no reported psychosocial interventions for depression in ethnic minorities in the UK., Aims: To determine the efficacy of a social group intervention compared with antidepressants, and whether the combination of the two is more efficacious than either alone., Method: A total of 123 women with depression participated in the primary care-based cluster randomised controlled trial (ISRCTN19172148). Outcome measures were severity of depression (Hamilton Rating Scale for Depression), social functioning and satisfaction at 3 and 9 months., Results: Greater improvement in depression in the social intervention group and the combined treatment group compared with those receiving antidepressants alone fell short of significance. There was significantly greater improvement in social functioning in the social intervention and combined treatment groups than in the antidepressant group at both 3 and 9 months., Conclusions: Pakistani women with depression found the social groups acceptable and their social function and satisfaction improved if they received social treatment compared with the receipt of antidepressants alone.

Aim: The Multidimensional Scale of Perceived Social Support (MSPSS) was developed to assess perceived social support, and has been widely used in Western samples. We attempted to translate and adapt this scale into the Urdu language, and herewith report on its psychometric properties in a rural Pakistani setting., Methods: The study sample consisted of 325 antenatal women who were registered with 'Lady Health Workers' in the Kallar Circle of Rawalpindi district. The subjects were assessed pre- and postnatally with measures of psychiatric distress, and social support and depression, respectively (using a guided structured interview)., Results: MSPSS scores were inversely related to measures of psychiatric distress and depression, thus supporting the construct validity of the MSPSS as a measure of social support. The internal consistency (Cronbach's alpha) of MSPSS was 0.92. Unlike previous research using the MSPSS in Western studies, the factor analysis revealed a single-factor solution that accounted for 53% of the variance., Conclusions: The Urdu translation of the MSPSS was found to have good construct validity, and internal consistency. However, the findings suggest that women in the study population perceived social support as a unitary construct, as opposed to a tri-dimensional one as identified in Western samples.

Background: Depression is common in Pakistan but no research on this subject has been reported from the North West Frontier Province (NWFP), host to numerous Afghan refugees., Aims: To measure depressive symptoms and associated features in a population-based sample., Method: A Pushto translation of the Self Reporting Questionnaire (SRQ) was administered to 471 adults living in a village in one of the federally administered tribal areas. Respondents were also assessed with a life events checklist for social problems, a social support questionnaire and the Brief Disability Questionnaire., Results: Sixty per cent (95/158) of women and 45% (140/313) of men scored 9 or more on the SRQ. High SRQ score was associated with few years of education, higher social problem score, less social support and greater disability. High social problem score was the strongest correlate., Conclusions: This population reports more depressive symptoms than other communities in Pakistan and this probably reflects the very high degree of social stress experienced in the NWFP, which has been affected by years of turmoilin neighbouring Afghanistan.

Background: The Personal Health Questionnaire (PHQ) was developed to screen for depressive disorder in an English speaking population. Its validity in Urdu speaking people of Pakistani family origin living in UK is yet to be established., Methods: The PHQ was used to screen for depression in a two phase primary care based study of depressive disorder in people of Pakistani family origin residing in Manchester, UK. A proportion of high scorers (PHQ> or =7) and a random selection of low scorers (PHQ 0-6) were interviewed with the Psychiatric Assessment Schedule (PAS) to confirm caseness (ID> or =5). A receiver operator characteristic curve (ROC) analysis was carried out to confirm the optimum threshold value., Results: The PHQ was used to screen 218 subjects with cut off of PHQ> or =7. 46 high scorers and 31 low scorers were interviewed in second stage using PAS. At this threshold PHQ has a sensitivity of 70.4% and specificity of 89.3%., Conclusions: Findings of this study confirm high sensitivity and specificity of PHQ amongst people of Pakistani family origin. It can be used as a screening instrument to detect depression in Urdu speaking population in UK.