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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. [ABSTRACT FROM AUTHOR]

To establish feasibility and acceptability of a Culturally adapted Family Intervention (CulFI) that was developed using an empirically derived conceptual framework in Pakistan. 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. 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. 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: NCT02167347 The 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 Pakistan A full-scale trial of CulFI in comparison with standard care is warranted to determine clinical and cost-effectiveness. [ABSTRACT FROM AUTHOR]

Background: Randomized controlled clinical trials that have investigated minocycline as an adjunctive treatment for major depressive disorder have proved promising. Data from two studies were pooled to evaluate more definitively whether the addition of minocycline to standard treatment for major depressive disorder leads to an improvement of depressive symptoms when compared with placebo. Methods: Both studies were multi-site, double-blinded, placebo-controlled trials of minocycline 200 mg/day added to treatment as usual during a 12-week period. The primary outcome measure was change in depressive symptoms (Montgomery–Asberg Depression Rating Scale in Dean et al. and Hamilton Depression Rating Scale in Husain et al.). Secondary outcomes were change in depression severity (Montgomery–Asberg Depression Rating Scale for Dean et al. and 9-item Patient Health Questionnaire in Husain et al.), anxiety severity (Hamilton Anxiety Rating Scale in Dean et al. and Generalized Anxiety Disorder 7-item scale in Husain et al.) and functional status, which were also evaluated as potential mediators on the primary outcome. Results: A total of 112 participants were included in the pooled data (Dean et al., n = 71; Husain et al., n = 41). A significant change from baseline to week 12 was noted in depressive symptoms – differential change (Placebo vs Minocycline): 9.0, 95% confidence interval = [4.2, 13.9], Cohen's D (95% confidence interval): 0.71 [0.29, 1.14], p < 0.001 – anxiety severity – differential change (Placebo vs Minocycline): 0.38, confidence interval = [0.00, 0.75], Cohen's D (95% confidence interval): 0.41 [0.00, 0.82], p = 0.050) and functional status – differential change (Placebo vs Minocycline): 1.0, 95% confidence interval = [0.4, 1.5], Cohen's D (95% confidence interval): 0.76 [0.34, 1.19], p = 0.001). Duration of illness, current use of benzodiazepine and pain medication were identified as moderators, whereas functional status as a mediator/predictor. Conclusion: The improvement of depressive symptoms, anxiety severity and functional status is promising and suggests that minocycline has potential as an adjunctive treatment for major depressive disorder. However, further studies are warranted to confirm therapeutic effects of minocycline in major depressive disorder. Trial registrations: NCT02263872, registered October 2014, and ACTRN12612000283875, registered March 2012. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

OBJECTIVE To explore the association of different variables and the role of Vortioxetine in managing suicidal ideation in patients suffering from depression in Pakistan. STUDY DESIGN This is a secondary-analysis of a large, multi-centre, noninterventional, prospective longitudinal study with patients who were prescribed Vortioxetine. PLACE AND DURATION OF THE STUDY The main study was conducted in 16 Psychiatry outpatient clinics in eight cities across Pakistan. The period of study was August 2019 to June 2020. SUBJECTS AND METHODS A total of 498 depressed patients aged 18- 65 years participated in the study. Suicidal ideation was measured using item number 9 of the Patient Health Questionnaire (PHQ-9). Participants were assessed at baseline, 1 week, 1-month and 3-month after treatment initiation. RESULTS There was statistically significant reduction in reporting of suicidal ideation from 80% at baseline to 13% at outcome assessment. There was significant positive correlation between suicidal ideation and cognitive dysfunction on Perceived Deficits Questionnaire (PDQ) and suicidal ideation and depression scores on PHQ-9. There was a statistically significant difference between those who reported suicidal ideation and those who did not report suicidal ideation on the clinical global impression-severity scale both at baseline and at 3-month outcome assessment. CONCLUSION Suicidal ideation is common in depressed patients and this study demonstrated that suicidal ideation was reduced significantly with Vortioxetine treatment. Future research is warranted to further confirm the findings with controlled groups. [ABSTRACT FROM AUTHOR]

Importance: Male postpartum depression is prevalent across populations; however, there is limited evidence on strategies to address it, particularly in low-income settings., Objective: To evaluate the effectiveness of Learning Through Play Plus Dads (LTP + Dads), a nonspecialist-delivered psychosocial intervention, in improving symptoms of male postpartum depression compared to treatment as usual., Design, Setting, and Participants: This cluster randomized clinical trial was conducted in Karachi, Pakistan, between June 2018 and November 2019. Assessors were blind to treatment allocation. Participants were recruited from 2 large towns in the city of Karachi via basic health units. Fathers aged 18 years and older with a DSM-5 diagnosis of major depressive episode and a child younger than 30 months were recruited. Of 1582 fathers approached, 1527 were screened and 357 were randomized in a 1:1 ratio to either the intervention or treatment as usual; 328 were included in the final analysis. Data were analyzed from April to June 2022., Interventions: LTP + Dads is a manualized intervention combining parenting skills training, play therapy, and cognitive behavior therapy. The intervention was delivered by community health workers via 12 group sessions over 4 months., Main Outcomes and Measures: The primary outcome was change in 17-item Hamilton Depression Rating Scale score at 4 months. Secondary outcomes included anxiety symptoms; parenting stress; intimate partner violence; functioning; quality of life; and child social, emotional, and physical health outcomes. Assessments were completed at baseline and 4 and 6 months postrandomization., Results: Of the 357 fathers included (mean [SD] age, 31.44 [7.24] years), 171 were randomized to the intervention and 186 to treatment as usual. Participants randomized to the intervention demonstrated significantly greater improvements in depression (group difference ratio [GDR], 0.66; 95% CI, 0.47 to 0.91; P < .001), anxiety (GDR, 0.62; 95% CI, 0.48 to 0.81; P < .001), parenting stress (GDR, -12.5; 95% CI, -19.1 to -6.0; P < .001), intimate partner violence (GDR, 0.89; 95% CI, 0.80 to 1.00; P = .05), disability (GDR, 0.77; 95% CI, 0.61 to 0.97; P = .03), and health-related quality of life (GDR, 12.7; 95% CI, 0.17 to 0.34; P < .001) at 4 months. The difference in depression and parenting stress was sustained at 6 months. Children of fathers randomized to the parenting intervention had significantly greater improvements in social-emotional development scores (mean difference, -20.8; 95% CI, -28.8 to -12.9; P < .001) at 6 months., Conclusions and Relevance: The psychosocial parenting intervention in this study has the potential to improve paternal mental health and child development in Pakistan. Further studies in other populations and with longer follow-up are warranted., Trial Registration: ClinicalTrials.gov Identifier: NCT03564847.

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.)