Mahesh Jayaram

Randomised trials relevant to mental health conducted in low and middle-income countries: a survey

BackgroundA substantial proportion of the psychiatric burden of disease falls on the worlds poorest nations, yet relatively little is known about randomised trials conducted in these countries. Our aim was to identify and describe a representative sample of mental health trials from low and middle-income countries.Methods6107 electronic records, most with full text copies, were available following extensive searches for randomised or potentially randomised trials from low and middle-income countries published in 1991, 1995 and 2000. These records were searched to identify studies relevant to mental health. Data on study characteristics were extracted from the full text copies.ResultsTrials relevant to mental health were reported in only 3% of the records. 176 records reporting 177 trials were identified: 25 were published in 1991, 45 in 1995, and 106 in 2000. Participants from China were represented in 46% of trials described. 68% of trials had <100 participants. The method of sequence generation was described in less than 20% of reports and adequate concealment of allocation was described in only 12% of reports. Participants were most frequently adults with unipolar depression (36/177) or schizophrenia (36/177). 80% of studies evaluated pharmacological interventions, a third of which were not listed by WHO as essential drugs. 41% of reports were indexed on PubMed; this proportion decreased from 68% in 1991 to 32% in 2000.ConclusionIn terms of overall health burden, trial research activity from low and middle-income countries in mental health appears to be low, and in no area adequately reflects need.

Prompt letters to reduce non-attendance: applying evidence based practice

BackgroundNon-attendance rates in psychiatric outpatient clinics have been a topic of considerable interest. It is measured as an indicator of quality of service provision. Failed attendances add to the cost of care as well as having an adverse impact on patients leading to missing medications, delay in identifying relapses and increasing waiting list time. Recent trials have demonstrated that prompting letters sent to patients led to a decrease in non-attendance rates. We applied this evidence based practice in our community mental health setting to evaluate its impact.MethodsUsing a before and after study design, we sent prompting letters to all patients due to attend outpatient clinic appointments for a period of six months in 2007. Non-attendance rates were compared with the corresponding period in 2006. We also looked at trends of non-attendance prior to this intervention and compared results with other parts of our service where this intervention had not been applied.Results1433 prompting letters were sent out to all out-patient appointments made from June to November 2007. This resulted in an average non-attendance rate of 17% which was significantly less compared to 27% between June and November 2006 (RR 0.65, 95% CI 0.56 to 0.76, NNT 11). No downward trend in non-attendance rate was identified either prior to the intervention or when compared with similar teams across the city.ConclusionPrompt letters have been shown to reduce non-attendance rates in previous RCTs and systematic reviews. Our findings demonstrate a reduction in non-attendance rates with prompting letters even under non-trial conditions. Majority of the patients were constant during the two periods compared although there were some changes in medical personnel. This makes it difficult to attribute all the change, solely to the intervention alone. Perhaps our work shows that the results of pragmatic randomised trials are easily applicable and produce similar results in non-randomised settings. We found that prompting letters are a useful and easy to apply evidence based intervention to reduce non-attendance rates with a potential to achieve significant cost savings.

Antidepressant prescribing in the precision medicine era: a prescriber's primer on pharmacogenetic tools

About half of people who take antidepressants do not respond and many experience adverse effects. These detrimental outcomes are in part a result of the impact of an individual’s genetic profile on pharmacokinetics and pharmcodynamics. If known and made available to clinicians, this could improve decision-making and antidepressant therapy outcomes. This has spurred the development of numerous pharmacogenetic-based decision support tools. In this article, we provide an overview of pharmacogenetic decision support tools, with particular focus on tools relevant to antidepressants. We briefly describe the evolution and current state of antidepressant pharmacogenetic decision support tools in clinical practice, followed by the evidence-base for their use. Finally, we present a series of considerations for clinicians contemplating use of these tools and discuss the future of antidepressant pharmacogenetic decision support tools.

Levomepromazine for Schizophrenia

Wesearched theCochrane SchizophreniaGroupTrialsRegister (December 2008), which is compiled by regular systematic searches of major databases including EMBASE, MEDLINE, and PsycINFO, the hand searching of relevant journals and conference proceedings, and searches of several key gray literature sources. References of all identified studies were inspected for further trials. We also contacted relevant pharmaceutical companies for additional information.

Twittering on about mental health: is it worth the effort?

The medical community disseminates information increasingly using social media. Randomised controlled trials are being conducted in this area to evaluate effectiveness of social media with mixed results so far, but more trials are likely to be published in the coming years. One recent twitter randomised control trial using Cochrane Schizophrenia Group reviews suggests that tweets increase the hits to the target web page by about threefold and time spent on the web page is also increased threefold when referrals come in via twitter. These are early findings and need further replication. Twitter appeals to professionals, entertainers and politicians among others as a means of networking with peers and connecting with the wider public. Twitter, in particular, seems to be well placed for use by the medical community and is effective in promoting messages, updating information, interacting with each other locally and internationally and more so during conferences. Twitter is also increasingly used to disseminate evidence in addition to traditional media such as academic peer-reviewed journals. Caution is required using twitter as inadvertent tweets can lead to censure. Overall, the use of twitter responsibly by the medical community will increase visibility of research findings and ensure up to date evidence is readily accessible. This should open the door for further trials of different social media platforms to evaluate their effectiveness in disseminating accurate high-quality information instantaneously to a global audience.

To tweet or not to tweet about schizophrenia systematic reviews (TweetSz): study protocol for a randomised controlled trial.

Introduction The Cochrane Schizophrenia Group (CSzG) has produced and maintained systematic reviews of effects of interventions for schizophrenia and related illness. Each review has a Plain Language Summary (PLS), for those without specialised knowledge, and an abstract, which are freely available from The Cochrane Library (https://summaries.cochrane.org). Increasingly, evidence is being distributed using social media such as Twitter and Weibo (in China) alongside traditional publications. Methods and analysis In a prospective two-arm, parallel, open randomised controlled trial with a 1:1 allocation ratio, we will allocate 170 published systematic reviews into the intervention group (tweeting arm/Weibo arm) versus the control group (non-tweeting arm). Reviews will be stratified by baseline access activity, defined as high (≥19 views per week, n=14), medium (4.3 to 18.99 views per week, n=72) or low (<4.3 views per week, n=84), based on Google Analytics, which will also be used for evaluating outcomes. The intervention group will have three tweets daily using Hootsuite with a slightly different accompanying text (written by CEA and AB) and a shortened Uniform Resource Locator (URL) to the PLS: a) The review title as it appears in summaries.cochrane.org, b) A pertinent extract from results or discussion sections of the abstract and c) An intriguing question or pithy statement related to the evidence in the abstract. The primary outcome will be: total number of visits to a PLS in 7 days following the tweet. Secondary outcomes will include % new visits, bounce rate, pages per visit, visit duration, page views, unique page views, time on page, entrances, exiting behaviour and country distribution. Ethics and dissemination This study does not involve living participants, and uses information available in the public domain. Participants are published systematic reviews, hence, no ethical approval is required. Dissemination will be via Twitter, Weibo and traditional academic means. Trial registration number ISRCTN84658943.

Randomised trials relevant to mental health conducted in low and middle-income countries: protocol for a survey of studies published in 1991, 1995 and 2000 and assessment of their relevance.

BackgroundA substantial proportion of the psychiatric burden of disease falls on the worlds poorest nations. Despite this, relatively little is known about the quality and content of clinical research undertaken in these countries, or the relevance of the interventions evaluated and specifically that of randomised trials.This project aims to survey the content, quality and accessibility of a sample of trials relevant to mental health conducted within low and middle-income countries; to compare these with studies conducted in high-income countries; and to assess their relevance for the needs of low and middle-income countries.MethodsAn extensive search for all trials, or possible trials, published in 1991, 1995 and 2000 with participants in low and middle-income countries has already been conducted. Studies evaluating prevention or treatment of a mental health problem within these three years will be identified and further searches conducted to assess completeness of the initial search. Data on study quality and characteristics will be extracted from each report. Accessibility will be estimated based on whether each citation is available on MEDLINE. Trials relevant to schizophrenia will be compared with a random sample of schizophrenia trials from high-income countries in the same years. Topics covered by the trials will be compared with the estimated burden of disease.ConclusionTrials and systematic reviews of trials are the gold standard of evaluation of care and increasingly provide the basis for recommendations to clinicians, to providers of care and to policy makers. Results from this study will present the first assessment of the scope, quality and accessibility of mental health trials in low and middle-income countries.

Why Cochrane should prioritise sharing data

Packer1 says that the one who submits a research for public good should be ready to receive a request for data sharing for examination and re-analysis and that tax payers assume that a national agency is checking such data and analysis. Here we discuss Cochrane’s practice on data sharing. Open science, as endorsed by the G7,2 includes sharing data, computer code, and materials. It is essential for reproducibility, collaboration, and innovation. We support the work of Cochrane, but are concerned that Cochrane is not sharing all its reviews’ data. These data should be fully accessible for reuse by third parties. Cochrane, a non-profit private company3 and registered charity, produces and maintains systematic reviews in health and social care. Its work is undertaken by a global network of thousands of people,4 and its support largely comes from public funding.5 Most people producing Cochrane reviews are volunteers not specifically funded for this work,67 and Cochrane encourages “crowdsourcing” of work.8910 Cochrane editorial bases help volunteers obtain study reports and manually extract the wealth of data needed to generate systematic reviews.111213 Cochrane teams use RevMan software14 to produce files in standard format (XML), storing information on the studies, their methods, and results for publication in the Cochrane Library. Benefits of sharing extracted data from trials and systematic reviews are well known, as are the costs of not sharing.13151617 Sharing maximises transparency, reliability of data extraction, and syntheses. It improves access to data—saving time and money—and opens new avenues of inquiry.18 Sharing is associated with increased citations,19 more publications,20 and reuse for new purposes.16 Structured data from Cochrane should be fully accessible for download, reuse, and review (box 1). Currently, they are not. …

Can we raise the standard of care in treating schizophrenia: A cautionary note!

Australian & New Zealand Journal of Psychiatry, 51(6) In an interesting and at times controversial paper (Catts and O’Toole, 2016), the authors examine an important and often overlooked area, namely, the progression of clinical and neurobiological changes in schizophrenia and how they may relate to the emergence of treatment-resistant disorder. The authors explore what underlies such changes and potential approaches to ameliorate them. We examine each of the issues considered, and raise alternative views on some of their conclusions, using the wellaccepted hierarchy of evidence pyramid, which gives the highest weighting to systematic review data of randomised controlled trials (RCT) (www.nhmrc.gov.au/_files_nhmrc/file/ guidelines/developers/nhmrc_levels_ grades_evidence_120423.pdf). The authors introduce the topic by using mortality rates (MR) as a measure of progress or lack of progress in the treatment of schizophrenia and infer that the outcomes of treatment are deteriorating over time. The authors note the increasing MR over time in schizophrenia as an indication that existing interventions have failed. The issue of MR is a complex one and can be divided into natural and unnatural causes. Natural causes include cardiovascular, neoplasms or other causes, and there is indeed some evidence of increased risk of cardiovascular deaths but not so for neoplasms. The strongest association, however, is between illicit drug use and unnatural deaths, which is high compared to the general population. The widening gap could also be explained by the actual life expectancy of individuals with schizophrenia remaining static, while that of the rest of the population has improved. To effectively address this apparent increase in MR gap, we need to understand the reasons better. In the subsequent paragraphs, we have addressed the key questions posed by the authors. In response to the first two questions, the authors ask whether schizophrenia is a progressive disease and whether relapse contributes to treatment resistance; they conclude that schizophrenia is a progressive-relapsing disease, resulting in ‘emergent treatment resistance in most cases’. Although there is now considerable evidence for brain changes longitudinally, a number of key questions remain unanswered, including the role of stress, illicit drug use, inactivity and role of maturational processes (Pantelis et al., 2005). Furthermore, there are limited data informing the hypotheses that relapse is associated with neurobiological changes (Cropley and Pantelis, 2014). The term treatment-resistant schizophrenia (TRS) has been around for a number of years; however, there is no consensus in defining it and the definition may vary depending on how response is defined. An extensive review and guideline concluded that 10–30% of patients have little or no response to antipsychotics and an additional 30% may have a partial response. Most of the studies summarized by the authors are based on symptom recovery rather than functional outcomes. A 97-year (1895–1992) meta-analysis involving >300 studies (51,800 patients) demonstrated that the rate of improved outcomes varied between 35% and 48%, with broader criteria associated with better prognosis (Hegarty et al., 1994). More recent studies suggest recovery occurs in a significant proportion of cases; however, outcome is based on a variety of prognostic factors (e.g. age of onset, duration of untreated psychosis, ethnicity). Hence, it would be simplistic to generalise that schizophrenia most often leads to treatment resistance. When should the diagnosis of schizophrenia be made? We agree with the author’s viewpoint that the diagnosis should be made at the earliest opportunity possible, and this applies to any stage of schizophrenia, not just first-episode psychosis (FEP). Indeed, diagnosis may be inconclusive during earlier illness stages. Instability in diagnosis may be related to early acute illness, wherein a clear trajectory has not yet emerged, and to drug-induced psychotic states that Can we raise the standard of care in treating schizophrenia: A cautionary note!

Rapid tranquillisation: a global perspective

Violence and aggression among patients suffering from mental health problems undoubtedly pose a challenge to healthcare professionals, families and carers. Aggressive behaviours affect all aspects of clinical care. The goal of professionals is to ensure safety while effectively managing behavioural emergencies. ‘Rapid tranquillisation’ implies prescribing pharmacological agents to manage these behaviours. This article highlights changing prescription trends. Appraisal of global guidelines suggests that factors other than scientific evidence dictate their evolution. High-quality randomised controlled trials are needed to develop a global guideline.