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 that 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 ARMS that are available both in high, low and middle-income countries. Methods A six-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. 320 consenting patients with capacity will be recruited from community, general practitioner clinics and psychiatric units. Allowing for a 25% dropout rate, we will recruit 59 completing participants to each study arm, and 236 will complete in total. We will determine whether the addition of minocycline and/or Omega-3 fatty acids to TAU attenuates 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 end-point is conversion to psychotic disorder at 12 months post study entry. Analysis will be by intention-to-treat, using analysis-of variance, chi-squared tests and adjusted odds ratios to assess between-group differences. Cox regression analyses will be used to analyse 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 evidenced, may prove to be safe and effective for treating ARMS

A mixed methods analysis of existing assessment and evaluation tools (AETs) for mental health applications

IntroductionMental health Applications (MH Apps) can potentially improve access to high-quality mental health care. However, the recent rapid expansion of MH Apps has created growing concern regarding their safety and effectiveness, leading to the development of AETs (Assessment and Evaluation Tools) to help guide users. This article provides a critical, mixed methods analysis of existing AETs for MH Apps by reviewing the criteria used to evaluate MH Apps and assessing their effectiveness as evaluation tools.MethodsTo identify relevant AETs, gray and scholarly literature were located through stakeholder consultation, Internet searching via Google and a literature search of bibliographic databases Medline, APA PsycInfo, and LISTA. Materials in English that provided a tool or method to evaluate MH Apps and were published from January 1, 2000, to January 26, 2021 were considered for inclusion.ResultsThirteen relevant AETs targeted for MH Apps met the inclusion criteria. The qualitative analysis of AETs and their evaluation criteria revealed that despite purporting to focus on MH Apps, the included AETs did not contain criteria that made them more specific to MH Apps than general health applications. There appeared to be very little agreed-upon terminology in this field, and the focus of selection criteria in AETs is often IT-related, with a lesser focus on clinical issues, equity, and scientific evidence. The quality of AETs was quantitatively assessed using the AGREE II, a standardized tool for evaluating assessment guidelines. Three out of 13 AETs were deemed ‘recommended’ using the AGREE II.DiscussionThere is a need for further improvements to existing AETs. To realize the full potential of MH Apps and reduce stakeholders’ concerns, AETs must be developed within the current laws and governmental health policies, be specific to mental health, be feasible to implement and be supported by rigorous research methodology, medical education, and public awareness

Prevalence of depression and anxiety in patients with chronic obstructive pulmonary disease and their association with psychosocial outcomes: A cross-sectional study from Pakistan.

ObjectivesChronic obstructive pulmonary disease contributes to substantial health and economic burden worldwide. Co-morbid depression and anxiety are highly prevalent in patients with chronic obstructive pulmonary disease. Depressive symptoms in chronic obstructive pulmonary disease are associated with poorer survival, longer hospitalisation and impaired quality of life. Literature on chronic obstructive pulmonary disease is largely derived from high-income countries; yet 90% of deaths related to chronic obstructive pulmonary disease occur in low- and middle-income countries. We aimed to establish the prevalence of anxiety and depression in patients with chronic obstructive pulmonary disease, as well as the association with psychosocial outcomes.MethodsThis was a cross-sectional study of chronic obstructive pulmonary disease patients attending outpatient primary care clinics in Karachi, Pakistan. The Patient Health Questionnaire-9 was used to assess depression and the Generalised Anxiety Disorder-7 scale was used for the assessment of anxiety. Health-related quality of life was assessed with EuroQol-Five Dimensions, social support with Oslo-3 and social stress with Life Events Checklist. We recruited 293 subjects.ResultsThe prevalence of depression and anxiety in the sample was 51% (n = 149) and 20% (n = 59), respectively. Depressed chronic obstructive pulmonary disease patients reported significantly lower health-related quality of life scores as compared to non-depressed patients. Participants with depression had significantly higher levels of anxiety, less social support, higher social stress and more subjective impairment in quality of life.ConclusionGiven the association with reduced social support and increased perceived stress, the role of psychosocial interventions must be explored in improving outcomes of chronic obstructive pulmonary disease patients in Pakistan

Stakeholders' views and opinions on existing guidelines on “How to Choose Mental Health Apps”

BackgroundMental health Applications (Mhealth Apps) can change how healthcare is delivered. However, very little is known about the efficacy of Mhealth Apps. Currently, only minimum guidance is available in Assessment and Evaluation Tools (AETs). Therefore, this project aims to understand AET developers' perspectives and end users' experiences and opinions on “how to choose a Mhealth App”.ObjectiveThe primary objectives were: (1) obtaining stakeholder's opinions and experiences of development and use of AETs for Mhealth Apps, their weaknesses and strengths, and barriers in their implementation of Mhealth Apps; (2) the experiences of App users, their analyzation and, obstacles in the use of apps; and (3) to quantify themes related to choosing a Mhealth App.MethodsThis qualitative study, used a sampling method to recruit six stakeholders (one App developer, two AET developers, an individual with lived experience of mental health illness, and two physicians) who were interviewed using a topic guide. These were examined by researchers (CT, WK, & FN) using thematic content analysis. Additionally, an anonymous online survey of 107 individuals was conducted.FindingsOur analyses revealed six main themes: (a) needs and opportunities; (b) views on Mhealth apps; (c) views & opinions on AETs; (d) implementation barriers; (e) system of evaluation and; (f) future directions. The first key concept was, all stakeholders agreed that Apps could significantly impact mental health and that end-users were unaware of mental health AETs and Apps. Secondly, due to commercial interests, end-users reliability of App evaluations requires clear conflict-free guidelines. Thirdly, AETs should be evaluated and developed through a rigorous methodology. Finally, stakeholders shared insights into future developments for AETs and Mhealth Apps. Additionally, online survey respondents chose a “health professional” as their preferred source of guidance in selecting a Mhealth app (84%) and best suited to develop guidelines (70%).ConclusionThe interviews and survey highlight the need for Mhealth Apps to be regulated and the importance of health professionals' engagement in the implementation process. Similarly, without well-defined roles for App evaluations within the health care system, it is unlikely that AETs will have wider spread use and impact without risk

Prevalence of suicidal ideation and suicide attempts in individuals with psychosis and bipolar disorder in South Asia: systematic review and meta-analysis.

BackgroundSuicidal ideation and attempts are growing public health concerns globally. Evidence from high-income countries suggests that individuals with psychosis and bipolar disorder are at increased risk of suicidal ideation and attempts, but there is a scarcity of evidence from South Asia.AimsTo estimate the prevalence of suicidal ideation and attempts in individuals with psychosis and bipolar disorder in South Asia.MethodIn this systematic review and meta-analysis, four databases (PsycINFO, Web of Science, EMBASE and Medline) were searched until December 2022. Pooled prevalence was estimated with random-effects models. Heterogeneity was quantified with the I2-statistic.ResultsThe pooled sample size across the 21 studies was 3745 participants, 1941 (51.8%) of which were male. The pooled prevalence of suicide attempts in South Asian people with either psychosis or bipolar disorder was 22% (95% CI 17-27; n = 15). The pooled prevalence of suicidal ideation with psychosis or bipolar disorder combined was 38% (95% CI 27-51; n = 10). Meta-regression, subgroup and sensitivity analysis showed that the pooled prevalence estimates for both suicide attempt and ideation remained unaffected by variations in critical appraisal ratings and study designs. Only one study reported data on suicide-related deaths.ConclusionsOne in four individuals diagnosed with psychosis or bipolar disorder have reported suicide attempts, whereas up to one in three have experienced suicidal ideation. These findings underscore the urgent need for clinicians to regularly assess and monitor suicidal ideation and attempts among individuals with these disorders in South Asia

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.

BackgroundInflammatory 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.Methods10,173 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.FindingsForty-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 InterpretationIn 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.FundingThe study was funded by the Stanley Research Medical Institute

The Toronto Adolescent and Youth Cohort Study:Study Design and Early Data Related to Psychosis Spectrum Symptoms, Functioning, and Suicidality

BACKGROUND: Psychosis spectrum symptoms (PSSs) occur in a sizable percentage of youth and are associated with poorer cognitive performance, poorer functioning, and suicidality (i.e., suicidal thoughts and behaviors). PSSs may occur more frequently in youths already experiencing another mental illness, but the antecedents are not well known. The Toronto Adolescent and Youth (TAY) Cohort Study aims to characterize developmental trajectories in youths with mental illness and understand associations with PSSs, functioning, and suicidality.METHODS: The TAY Cohort Study is a longitudinal cohort study that aims to assess 1500 youths (age 11-24 years) presenting to tertiary care. In this article, we describe the extensive diagnostic and clinical characterization of psychopathology, substance use, functioning, suicidality, and health service utilization in these youths, with follow-up every 6 months over 5 years, including early baseline data.RESULTS: A total of 417 participants were enrolled between May 4, 2021, and February 2, 2023. Participants met diagnostic criteria for an average of 3.5 psychiatric diagnoses, most frequently anxiety and depressive disorders. Forty-nine percent of participants met a pre-established threshold for PSSs and exhibited higher rates of functional impairment, internalizing and externalizing symptoms, and suicidality than participants without PSSs.CONCLUSIONS: Initial findings from the TAY Cohort Study demonstrate the feasibility of extensive clinical phenotyping in youths who are seeking help for mental health problems. PSS prevalence is much higher than in community-based studies. Our early data support the critical need to better understand longitudinal trajectories of clinical youth cohorts in relation to psychosis risk, functioning, and suicidality.</p

Medically unexplained symptoms—a perspective from general practitioners in the developing world

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. </jats:sec

Targeting Metabolic Dysfunction for the Treatment of Mood Disorders: Review of the Evidence

Major depressive disorder (MDD) and bipolar disorder (BD) are often chronic with many patients not responding to available treatments. As these mood disorders are frequently associated with metabolic dysfunction, there has been increased interest in novel treatments that would target metabolic pathways. The objectives of this scoping review were to synthesize evidence on the impact on mood symptoms of lipid lowering agents and anti-diabetics drugs, while also reviewing current knowledge on the association between mood disorders and dyslipidemia or hyperglycemia. We propose that metabolic dysfunction is prevalent in both MDD and BD and it may contribute to the development of these disorders through a variety of pathophysiological processes including inflammation, brain structural changes, hormonal alterations, neurotransmitter disruptions, alteration on brain cholesterol, central insulin resistance, and changes in gut microbiota. Current evidence is conflicting on the use of statins, polyunsaturated fatty acids, thiazolidinediones, glucagon-like peptide agonists, metformin, or insulin for the treatment of MDD and BD. Given the paucity of high-quality randomized controlled trials, additional studies are needed before any of these medications can be repurposed in routine clinical practice. Future trials need to enrich patient recruitment, include evaluations of mechanism of action, and explore differential effects on specific symptom domains such as anhedonia, suicidality, and cognition