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

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

Culturally adapted motivational interviewing with cognitive behavior therapy and mindfulness-based relapse prevention for substance use disorder in Pakistan (CAMAIB): protocol for a feasibility factorial randomised controlled trial.

BACKGROUND: The use of psychoactive substances significantly impacts the health, social and economic aspects of families, communities and nations. There is a need to develop and test psychological interventions aimed for individuals with substance use disorder (SUD) in lower- and middle-income countries (LMICs), such as in Pakistan. The aim of this exploratory trial is to test the feasibility and acceptability of two culturally adapted psychological interventions in a factorial randomised controlled trial (RCT). METHODS: The proposed project will be conducted in three phases. The first phase of the study will focus on cultural adaptation of the interventions through qualitative interviews with key stakeholders. The second phase will be to refine and produce manually assisted interventions. Third and last stage would be to assess the feasibility of the culturally adapted interventions through a factorial RCT. The study will be carried out in Karachi, Hyderabad, Peshawar, Lahore and Rawalpindi, Pakistan. Recruitment of participants will take place from primary care and volunteer organisations/drug rehabilitation centres. A total of 260 individuals diagnosed with SUD (n = 65) in each of the four arms will be recruited. The intervention will be delivered weekly over a period of 12 weeks in both individual and group settings. Assessments will be carried out at baseline, at 12th week (after completion of intervention) and 24th week post-randomisation. The analysis will determine the feasibility of recruitment, randomisation, retention and intervention delivery. Acceptability of intervention will be determined in terms of adherence to intervention, i.e. the mean number of sessions attended, number of home assignments completed, attrition rates, as well as through process evaluation to understand the implementation process, context, participants' satisfaction, and impact of the study intervention. The health resource use and impact on the quality of life will be established through health economic data. DISCUSSION: This study will provide evidence for feasibility and acceptability of culturally adapted manually assisted psychological interventions for individuals with SUD in the context of Pakistan. The study will have clinical implications if intervention is proven feasible and acceptable. TRIAL REGISTRATION: Name of the registry: ClinicalTrials.gov, Trial registration number: NCT04885569 , Date of registration: 25th April 2021.

What works? Lessons from a pretrial qualitative study to inform a multi-component intervention for refugees and asylum seekers: Learning Through Play and EMDR Group Traumatic Episode Protocol.

Almost half of the trials failed to recruit their targeted sample size of which 89% could be preventable. Successful implementation of mental health trials in a context of forcibly displaced individuals can be even more challenging. Mental health difficulties have the potential to impact parenting skills, which are linked to poor development in children, while parenting interventions can improve parents' mental health and parenting behaviors. However, the evidence on parenting interventions for refugees is limited. A parenting intervention, Learning Through Play Plus Eye Movement Desensitization and Reprocessing Group Treatment Protocol, has been designed to address parental mental health. This pretrial qualitative study, conducted with refugees, asylum seekers and professionals, aimed to explore their perceptions of the intervention and to identify barriers and recommendations for better engagement, recruitment, and delivery. Three themes were generated from thematic analysis: the content of the intervention, suggestions for improvement and implementation, and understanding the role of the facilitator. These themes provided insights into the issues that might predict the barriers for delivery of the intervention and offered several changes, including destigmatization strategies to improve engagement.

Group eye movement desensitization and reprocessing interventions in adults and children: A systematic review of randomized and nonrandomized trials.

This review systematically synthesized existing literature on group protocols of eye movement desensitization and reprocessing (EMDR) therapy for treating a range of mental health difficulties in adults and children. We conducted database searches on PsychINFO, EMBASE, MEDLINE, Web of Science, The Cochrane Library and Francine Shapiro Library up to May 2020, using PRISMA guidelines. Studies were included if they used at least one standardized outcome measure, if they present a quantitative data on the effect of group EMDR protocols on mental health difficulties and if they were published in English. Twenty-two studies with 1739 participants were included. Thirteen studies examined EMDR Integrative Group Treatment Protocol (IGTP), four studies examined EMDR Group Traumatic Episode Protocol (G-TEP), four studies EMDR Integrative Group Treatment Protocol for Ongoing Traumatic Stress and one study considered EMDR Group Protocol with Children. Of the 22 studies included, 12 were one-arm trials and 10 were two-arm trials. We assessed risk of bias using a revised Tool to Assess Risk of Bias in Randomized Trials (ROB 2) and Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I). Overall, the results suggested that Group EMDR protocols might be an effective tool in improving a wide range of mental health-related outcomes including posttraumatic stress disorder (PTSD), depression and anxiety. However, the included studies are limited to methodological challenges. The limitations and future directions are discussed.

Protocol of a feasibility trial for an online group parenting intervention with an integrated mental health component for parent refugees and asylum-seekers in the United Kingdom: (LTP + EMDR G-TEP).

OBJECTIVES: Conflicts expose families to a range of factors that could have a negative impact upon parental mental health which in turn leads to poor growth and development of children. Early support can improve parental mental health and parenting behaviours but currently, there is a lack of evidence on parenting interventions for forcibly displaced populations. This study aims to deliver an online parenting intervention with a mental health component for refugee and asylum-seeker parents to evaluate its feasibility and acceptability. METHODS: This is a single-arm trial without a control group. The trial aims to recruit 14 refugee and asylum-seeker parents into an Online Learning Through Play and Eye Movement Desensitization and Reprocessing Group Traumatic Episode Protocol (LTP + EMDR G-TEP). The intervention will be delivered by trained research team members using online platforms. RESULTS: The participants' sense of parenting competence, symptoms of traumatic stress, anxiety and depression will be measured at baseline and post-intervention. Semi-structured interviews at post-intervention will also be conducted. DISCUSSION: This study will assess the feasibility and inform the design of a future randomized controlled trial which aims to evaluate the effectiveness of LTP + EMDR G-TEP intervention for parent refugees and asylum-seekers with young children.

A randomised, double-blind, placebo-controlled trial of minocycline and/or omega-3 fatty acids added to treatment as usual for at-risk mental states (NAYAB): study protocol.

BACKGROUND: The at-risk mental state (ARMS) describes individuals at high risk of developing schizophrenia or psychosis. The use of antipsychotics in this population is not supported, because most individuals with ARMS are unlikely to develop psychosis. Anti-inflammatory treatments and polyunsaturated fatty acids (PUFAs) may have some beneficial effects in the treatment of ARMS. There have been no controlled clinical trials in which researchers have investigated the use of minocycline for ARMS and no trials involving PUFAs in combination with other proposed treatments. There is a need to find effective, tolerable and inexpensive interventions for individuals with ARMS that are available in high-, low- and middle-income countries. METHODS/DESIGN: A 6-month intervention study of minocycline and/or omega-3 fatty acids added to treatment as usual (TAU) in patients with ARMS will be conducted in Pakistan using a randomised, placebo-controlled, double-blind factorial design. A total of 320 consenting patients with capacity will be recruited from the community, general practitioner clinics and psychiatric units. Allowing for a 25% dropout rate, we will recruit 59 completing participants into each study arm, and in total 236 will complete the study. We will determine whether the addition of minocycline and/or omega-3 fatty acids to TAU attenuates the rate of transition from ARMS to first-episode psychosis and improves symptoms and/or level of functioning in ARMS. We will also investigate whether any candidate risk factors, such as negative symptoms, influence treatment response in the ARMS group. The primary efficacy endpoint is conversion to psychotic disorder at 12 months after study entry. Analysis will be done according to the intention to treat principle using analysis of variance, chi-square tests and adjusted ORs to assess between-group differences. Cox regression analysis will be used to evaluate potential between-group differences in time to onset of psychosis. DISCUSSION: The outcomes of this trial will provide evidence of the potential benefits of minocycline and PUFAs in the treatment of ARMS. Both minocycline and PUFAs are inexpensive, are readily available in low-/middle-income countries such as Pakistan, and if proven, may be safe and effective for treating individuals with ARMS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02569307 . Registered on 3 October 2015.

Explanatory models of psychosis amongst British South Asians.

PURPOSE: A strong interest in the understanding, exploring, and extracting explanatory models of psychosis has recently arisen. Explanatory models (EMs) offer justifications and propose explanations when coping with and treating illnesses. Therefore, they may be important predictors of clinical outcome. Explanatory models of psychosis have been explored in many non-Western countries. However, very little research has examined EMs of psychosis in the UK. We therefore, aimed to elicit and describe explanatory models of psychosis amongst British South Asians, using both quantitative and qualitative methods. METHOD: EMs of psychosis were examined using the Short Explanatory Model Interview (SEMI) in a cross-sectional sample of 45 patients. RESULTS: Most patients (55.5%) attributed their illness to supernatural causes. Few patients cited a biological (4.4%) cause. Majority of patients held dual EMs of psychosis (77.7%), combining prescribed medication and seeing a traditional healer as a treatment method. Duration of Untreated Psychosis (DUP) was not significantly associated with EMs of psychosis. CONCLUSION: The results suggest that patients hold multi-explanatory models in order to make sense of their illness and these stem from deep rooted traditional beliefs. This highlights the importance of educational intervention, culturally adapted psychological interventions and possibly working together with traditional healers in the UK to provide a positive support system. Further work is required in order to fully understand the relationship between EMs of psychosis and DUP.