‘We have some great ideas, but most of ‘em come too late to do us any good’. Will Rogers (American humorist, 1933) In contrast with mainstream health care, early diagnosis and intervention has come late to the field of psychiatry. People with potentially severe disorders, such as depression, schizophrenia, bipolar disorder, substance use disorders and borderline personality disorder typically enter treatment late or not at all. This is due to a number of factors, notably the neglect and consequently variable quality of most psychiatric services, their disconnection from mainstream medicine, stigma and unwarranted pessimism about the effectiveness of treatments in psychiatry. In psychiatry, the syndromal nature of diagnosis and widespread comorbidity means that a focus on a single syndromal target for early intervention may be counterproductive. Building on the exponential progress in early psychosis over the past decade, as well as widespread interest around the world in preventive psychiatry, we believe it is now timely to create a broad early intervention focus, and launch a platform for researchers and clinicians working across the full spectrum of disorders and with a special interest in their early phases, to share and promote ideas, experience and data. Early Intervention in Psychiatry will stimulate new interest among a broad range of professionals and help to develop a new international critical mass in preventive psychiatry. The journal’s biopsychosocial perspective will provide an integrating force to condense findings across aetiopathological domains and intervention strategies. By incorporating a health services and policy focus, Early Intervention in Psychiatry will help guide reform in mental health in an evidence-based manner and act as a resource for policy makers and planners. Evidence should be the life-blood for lasting reform, yet useful evidence is in short supply. Moreover, practical reform is heavily overdetermined, driven also by ideas, advocacy, economic and cultural factors and feasibility considerations. Reform cannot always wait for perfect evidence, because the lack of positive change leads to decay. In most areas of psychiatry we still lack key pieces of evidence, yet paradoxically the evidence we have is often not applied in the real world to help patients and their families. In this scenario, the best available evidence can nevertheless be used to support ‘best bets’ in gaining value for money and optimizing health outcomes. Because on the one hand, primary prevention remains elusive, while on the other the bulk of resources are expended on reactive acute care and palliation, early intervention is on any analysis a ‘best bet’. For a variety of reasons, sociological as well as scientific, early diagnosis and intervention represents one of the last frontiers in psychiatry. Early intervention could release the much vaunted potential of the neuroscience revolution in a practical way and catalyse a new wave of treatment approaches and models of care. Even with existing levels of knowledge, a simple change of focus and emphasis could deliver better outcomes for people with potentially severe mental and substance use disorders. The earlier stages of such disorders are likely to be more responsive to interventions, which may be correspondingly safer and more benign, as witnessed in mainstream medicine, notably oncology and cardiology. In recent years, international interest in early intervention has grown exponentially in psychotic disorders, arguably the least promising arena for such progress, given the entrenched pessimism that has engulfed schizophrenia since its birth as a concept over 100 years ago. There have been calls to develop a journal for early psychosis during the past decade; however, we believed psychosis as a sole focus did not warrant a new early intervention journal and delayed this step. The genesis of this journal has come after much debate and reflection. We hope that Early Intervention in Psychiatry, with its much wider mandate, will be a more useful and ultimately sustainable proposition, which will contribute much more substantially to progress in psychiatry and the mental health field in general. This decision is supported by the results of an international consultation process, and we are confident that the journal will not only fill a gap, but also help to create and extend a missing frontier in academic and clinical psychiatry. Early Intervention in Psychiatry is needed because there is a burgeoning literature in early psychosis, which captures a significant proportion of journal and conference space already, especially in the schizophrenia and psychosis domain. Without a new journal it will be difficult to extend the reach of this paradigm into other disorders. This journal will seek to draw upon and merge the disparate literature from disorder-specific forums. The major general psychiatry journals cannot comprehensively do this as they must embrace not only all disorders, but all aspects of psychiatry. A cross-disorder focus, but with a focus on the early phases of disorder, is a unique strategy that should progress the field more rapidly. The aims of Early Intervention in Psychiatry are therefore as follows: to promote the scientific study of the early phases of mental and substance use disorders, and their early detection, diagnosis and treatment; to promote and extend early diagnosis and phase-specific treatment in psychiatry; and to illuminate the underlying pathophysiology and clinical epidemiology of onset and early course of disorder. The ultimate aim is to ensure that early diagnosis and preventive intervention become as well accepted in psychiatric practice as they are in mainstream health care. Early Intervention in Psychiatry will seek to be an international journal of the finest quality. The editorial team is keen to fulfil this role because they believe this is the last frontier in psychiatry, and, if significant progress is made here, then health outcomes for people with serious mental illness can be substantially improved. Deeper understanding of the early phases of disorder may also represent a gateway to major advances in aetiology and treatment. We want Early Intervention in Psychiatry to be a critical tool in catalysing progress in serious mental disorders. We are highly motivated around this goal and see the journal as a central strategy for more effective growth upon a scientific base. We hope and expect to receive support from all parts of the world in this task, and invite researchers, clinicians, consumers and families, policy makers and our communities to participate in this challenge.
Advocacy for early intervention in psychiatry as described in the first issue of this Journal1, 2 includes a call to bring the rationale of public health and prevention to the improvement of mental health. Even though much of the research on early intervention in psychiatry is conducted in rich countries, the call is even more relevant to low-income countries where the needs are higher and the treatment and research gaps wider.3, 4 Poverty, gender-based violence and other determinants of poor mental health are also more prevalent in low-income countries. The moral case for international mental health5 has at its centre ‘the need to reclaim the place of mental health at the heart of international public health’ (p. 1312). The failure to do this is linked with the perception that mental health is a luxury for rich people in wealthy countries, and related to the well-known paradox that those most in need receive the least in attention and resources. Early intervention and other public health actions need consideration as important components of the response to poor mental health in the populations of all countries. The temptation for services, governments and non-government organizations in the face of overwhelming distress and disability related to mental illnesses in low income countries is to concentrate exclusively on those with established illnesses and neglected needs for acute treatment and rehabilitation. Experience from the rest of medicine, however, along with emerging evidence for early intervention, suggest that the effective and efficient response in countries to mental health needs will be seen to include additional components: attention to the needs for early intervention, as well as health promotion and prevention of other types.6, 7 Public health is defined as the organized global and local effort to promote and protect the health of populations and to reduce health inequities.8 Yet for many professionals and non-professionals whose experience is institutionalized care for people living with apparently entrenched illnesses and disabilities, early intervention, prevention of illnesses and the promotion of mental health are seen as removed from the most urgent problems and even as diverting resources from these. On the contrary, in low-income countries the needs for early intervention, along with prevention and health promotion, are based on the need to avert episodes of illness as well as avoid the losses in health and productivity that accompany poor mental health for patients and families. The epidemic of pesticide ingestion in many poorly resourced countries,9 for example, requires early intervention in mental health problems as an important part of the solution. Across a range of disorders the needs for early intervention are higher and the available evidence base weaker in low-income countries. The choice is either to improve the evidence base or to wait and see while early intervention finds its feet in the rich world. The extent of need and its rates of growth, as well as the emerging evidence for early intervention make the latter a risky choice. The Lancet Series on global mental health (to be published in September 2007) summarizes the evidence on cost-effective interventions for the treatment and prevention of mental disorders in low- and middle-income countries, and provides the rationale to scale up mental health services and prevention activities at the country level. There is strong evidence of the effectiveness of both drug and psychosocial treatments for common mental disorders including depression. Strong evidence also exists for pharmacological and community and family-based models of care for people with psychotic disorders including studies on the treatment of first episode disorders. There is modest evidence in support of primary care-based interventions for hazardous alcohol use, another problem with a high burden in many low-income countries. This work emphasizes the need for further research, including research in early intervention across these and other conditions. Early intervention needs to be placed on country agendas when considering mental health policy and practice, as the opportunities for research and appropriate service development will otherwise be lost. Unless service systems are established with this possibility in mind, the work cannot easily be imagined or proceed. The work of non-government organizations in rural and urban areas of several countries gives an indication of feasible early intervention at low cost along with community-based rehabilitation.10 Common program elements include community-based workers who may or may not have previous professional training, trained and supervised by the scarce mental health professionals. The workers interact with participating families and community groups that identify those with onset of illness as well as support those receiving treatment and rehabilitation. The workers are often supported by stepped care programs where needs are met by appropriate referrals in an organized care structure. Careful organization and management are required, but the resources used are a fraction of those used by service systems in wealthier countries. The work in these systems needs evaluation. The development of research capacity through collaborations with researchers in other countries can help this occur. Placing the support for such research and research capacity development in mental health on the agenda of the major national and international development agencies, financial institutions and foundations is an important task for advocates of early intervention and advocates for the improvement of mental health more generally. The barriers to the development of evidence-based capacity for early intervention in developing countries are the same as those in all countries2 and for any service development, though the difficulties are magnified. These notably include stigma, unwarranted pessimism about the effectiveness of treatments and capacity to deliver these, and exiguous resources dedicated to mental health. The solutions, however, can be different and innovative. Such solutions properly characterized and evaluated can inform service development in better-resourced countries and settings, where avoidable disability and poor service coordination remain common of those receiving care.
AIM: To assess: (i) trainees' educational needs on early intervention in psychiatry; (ii) their satisfaction and competence in early detection and management of patients with severe mental disorders; (iii) characteristics of training on prevention and on early intervention in psychiatry; and (iv) organizational and clinical differences of early intervention programmes and services in different countries. METHODS: Sixty early career psychiatrists, recruited from the early career psychiatrists' network of the World Psychiatric Association, were invited to participate in the survey. Respondents were asked to provide the collective input of their trainees' association rather than that of any individual officer or member. An online survey was conducted using an ad hoc questionnaire consisting of 18 items. RESULTS: Thirty-five countries sent back the questionnaire (58.3%). University training in early intervention for mental disorders was provided in 13 countries (38%); 54% of respondents were not satisfied with received training and about half of them did not feel enough confident to provide specialistic interventions to patients at the onset of the disorder. Services for early intervention existed in 22 countries (63%). The most frequently available were those for schizophrenia (75%). Informative campaigns on mental disorders were usually carried out in almost all surveyed countries (85%). CONCLUSIONS: Although prevention and early intervention represent one of the current paradigms of psychiatric practice and research, efforts are still needed in order to improve training programmes at university sites.
Psychotic disorders and particularly schizophrenia are serious and sometimes fatal illnesses which typically emerge during the sensitive developmental period of adolescence and emerging adulthood 1. For over a century, a corrosive blend of pessimism, stigma and neglect have confined therapeutic efforts to delayed and inconsistent palliative care. Much of this can be attributed to the conceptual error underpinning the concept of schizophrenia, namely that a true disorder could be validly defined by its (poor) outcome. This error was, in turn, a legacy of the 19th century degeneration theory, which has been allowed to influence the field well beyond its use-by date 2. Although Kraepelin himself and some of his contemporaries ultimately recognized the fallacy, his dichotomy (between dementia praecox and manic depressive insanity) has withstood several challenges and has been strongly reinforced with the advent of operational diagnostic systems. This has not only hampered neurobiological research, but has caused widespread iatrogenic harm and inhibited early diagnosis because of an exaggerated fear of the expected outcome. Until recently, apart from transient and illusory optimism generated by the mental hygiene movement in the 1920s, early intervention for psychotic disorders has been the furthest thing from the minds of clinicians and researchers. Ironically, however, since the early 1990s, this hitherto barren landscape has seen the growth of an increasingly rich harvest of evidence, and widespread national and international efforts for reform in services and treatment approaches, setting the scene for more serious efforts in early intervention in other mental disorders 3–5. Building on seminal research on first episode psychosis from the 1980s 6–8, frontline early psychosis clinical services were established, first in Melbourne 9 and soon after in many key locations in the UK, Europe, North America and Asia 10. There are now hundreds of early intervention programs worldwide, of varying intensity and duration, which focus on the special needs of young people and their families. International clinical practice guidelines and a consensus statement have been published 11 and clinical practice guidelines for the treatment of schizophrenia now typically have a major section on early psychosis 12,13. The International Early Psychosis Association (www.iepa.org.au), an international organization which seeks to improve knowledge, clinical care and service reform in early psychosis, has been in existence for over ten years, led by a highly collegial leadership group of clinicians and researchers. This association has over 3000 members from over 60 different countries, and by 2008 will have held six international conferences, stimulating and capturing a large volume of research and experience. In recent months, responding to the widespread international momentum, the US National Institute of Mental Health has announced a large new funding initiative to study and promote the development of better services for patients with first episode psychosis (www.nimh.nih.gov). The advent of preventive thinking has required a shift in the way schizophrenia and other psychotic disorders are viewed. Rather than seeing them as having inevitably poor prognoses with deterioration in social and functional outcome as the norm, more recent thinking backed up by evidence from large international studies 14–25 views the course of these disorders as much more fluid and malleable. Examination of risk factors which can influence outcome has revealed that many of these may be reversible. For example, disruption of peer and family networks and vocational drop-out commonly occur around and even before the onset of a first psychotic episode. Attention to these areas as part of treatment has the potential to limit or repair the damage. Comorbid depression, substance use, personality dysfunction and post-traumatic stress disorder (PTSD) are all factors which may influence outcome in a person with first episode psychosis. Again, early and vigorous management of these problems can result in better outcomes 26. Early intervention is a potentially confusing term. Because there is no aetiopathological basis for diagnosing psychotic disorders, they can only be diagnosed by symptoms or combinations of symptoms. In addition, we have no known malleable causal risk factors which predict onset of psychotic disorder with any specificity. Thus, it seems that primary prevention is currently out of our reach. Early intervention, therefore, means early secondary prevention. In keeping with the clinical staging model 27 articulated below, early intervention in psychosis can be defined as comprising three foci or stages: ultra-high risk, first episode, and the recovery or critical period. The principal reason for making such distinctions relates to the underlying risk of chronicity, and specifically the timing and duration of prescription of antipsychotic medication, since psychosocial interventions are needed at all stages, though these interventions too vary by stage. Clinicians and researchers have debated whether to focus on the preventive target of schizophrenia or of psychotic disorders more broadly. There are several reasons for stepping out of the current diagnostic silos and preferring a relatively broad target. As described above, schizophrenia is conceived and defined in part as an outcome as much as a diagnosis. While it is very stable once applied 28–31, it is intrinsically difficult to apply until the patient has been ill for a prolonged period of time. Within a sample of ultra-high risk cases (already defined in order to preferentially predict transition to non-affective psychosis), only 75% of those who go on to develop a first episode psychosis will progress to a schizophrenia diagnosis 32. So, the false positive rate is higher for schizophrenia than for first episode psychosis. Even within a first episode psychosis sample, only 30–40% will meet criteria for schizophrenia, and this percentage will increase over time with additional diagnostic flux. Thus, some cases of first episode psychosis which do not meet criteria for schizophrenia can be seen as being at risk for this in the future 33. Schizophrenia, therefore, is to some extent a more distal target than psychosis, which is a better and broader initial waystation for critical treatment decisions. An even earlier and broader point for intervention is the ultra-high risk clinical stage, where there is a need for care prior to the positive psychotic symptoms having become severe and sustained. In addition, due to fear and stigma derived from the notion of intrinsic poor prognosis, clinicians are reluctant to use the label “schizophrenia” early on anyway, justifiably concerned about iatrogenic effects on hope and the potential for recovery 34. This has led some countries, such as Japan, to change their diagnostic terminology and eschew the word “schizophrenia” 35. Our preferred alternative is to retain it for the time being, as one subtype of psychotic disorder outcome, admittedly a major one, among a small range of distal targets. Psychosis itself is a variable syndrome, defined by the presence of positive psychotic symptoms, especially delusions and hallucinations, and typically features one or many comorbidities, including negative symptoms, mood syndromes, personality disorders, substance use disorders, medical diseases and PTSD. The relative prominence of the positive symptoms and comorbidities varies, and this leads to a more hetero-geneous group of patients. As a consequence of this, a broader range of clinical skills will be required in early psychosis programs than in narrower schizophrenia programs. Some have argued that the schizophrenia focus allows the other psychotic disorders, especially psychotic mood disorders and psychoses associated with certain personality disorders and PTSD, to be treated in more appropriate settings. However, provided there is a flexible attitude and a broad range of clinical expertise available, both groups of patients benefit more from this broad, early, and inclusive focus on the spectrum of psychosis. It provides a good balance between specialization and addressing common needs, and also facilitates both clinical and aetiological research, which increasingly needs to transcend traditional diagnostic barriers. Many of the problems of categorical diagnosis flow from a telescoping of syndromes and stages of illness which conceals and distorts the natural ebb and flow of illness, remission and progression. In addition to augmenting categorical approaches with symptom dimensions, consideration needs to be given to the dimensions of time, severity, persistence and recurrence. The notion of staging can be borrowed and adapted from mainstream medicine to assist us here. A clinical staging model provides a heuristic framework allowing the development and evaluation of broad and specific interventions as well as the study of the variables and processes underlying the evolution of psychiatric disorder 27,36. Clinical staging is simply a more refined form of diagnosis 37,38. Its value is recognized in the treatment of malignancies, where quality of life and survival rely on the earliest possible delivery of effective interventions. However, it also has applicability in a diverse range of diseases. Clinical staging differs from conventional diagnostic practice in that it defines the extent of progression of disease at a particular point in time, and where a person lies currently along the continuum of the course of illness 36. The differentiation of early and milder clinical phenomena from those that accompany illness extension, progression and chronicity lies at the heart of the concept. It enables the clinician to select treatments relevant to earlier stages, and assumes that such interventions will be both more effective and less harmful than treatments delivered later in the course. While staging links treatment selection and prediction, its role in the former is more crucial than in the latter, particularly since early successful treatment may change the prognosis and thus prevent progression to subsequent stages. In addition to guiding treatment selection, a staging framework, which moves beyond the current diagnostic silos to encompass a broader range of clinical phenotypes, and which at the same time introduces subtypes along a longitudinal dimension, has the potential to organize endophenotypic data in a more coherent and 36. 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BACKGROUND: Excessive drinking is a significant cause of mortality, morbidity and social problems in many countries. Brief interventions aim to reduce alcohol consumption and related harm in hazardous and harmful drinkers who are not actively seeking help for alcohol problems. Interventions usually take the form of a conversation with a primary care provider and may include feedback on the person's alcohol use, information about potential harms and benefits of reducing intake, and advice on how to reduce consumption. Discussion informs the development of a personal plan to help reduce consumption. Brief interventions can also include behaviour change or motivationally-focused counselling.This is an update of a Cochrane Review published in 2007. OBJECTIVES: To assess the effectiveness of screening and brief alcohol intervention to reduce excessive alcohol consumption in hazardous or harmful drinkers in general practice or emergency care settings. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and 12 other bibliographic databases to September 2017. We searched Alcohol and Alcohol Problems Science Database (to December 2003, after which the database was discontinued), trials registries, and websites. We carried out handsearching and checked reference lists of included studies and relevant reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of brief interventions to reduce hazardous or harmful alcohol consumption in people attending general practice, emergency care or other primary care settings for reasons other than alcohol treatment. The comparison group was no or minimal intervention, where a measure of alcohol consumption was reported. 'Brief intervention' was defined as a conversation comprising five or fewer sessions of brief advice or brief lifestyle counselling and a total duration of less than 60 minutes. Any more was considered an extended intervention. Digital interventions were not included in this review. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We carried out subgroup analyses where possible to investigate the impact of factors such as gender, age, setting (general practice versus emergency care), treatment exposure and baseline consumption. MAIN RESULTS: We included 69 studies that randomised a total of 33,642 participants. Of these, 42 studies were added for this update (24,057 participants). Most interventions were delivered in general practice (38 studies, 55%) or emergency care (27 studies, 39%) settings. Most studies (61 studies, 88%) compared brief intervention to minimal or no intervention. Extended interventions were compared with brief (4 studies, 6%), minimal or no intervention (7 studies, 10%). Few studies targeted particular age groups: adolescents or young adults (6 studies, 9%) and older adults (4 studies, 6%). Mean baseline alcohol consumption was 244 g/week (30.5 standard UK units) among the studies that reported these data. Main sources of bias were attrition and lack of provider or participant blinding. The primary meta-analysis included 34 studies (15,197 participants) and provided moderate-quality evidence that participants who received brief intervention consumed less alcohol than minimal or no intervention participants after one year (mean difference (MD) -20 g/week, 95% confidence interval (CI) -28 to -12). There was substantial heterogeneity among studies (I² = 73%). A subgroup analysis by gender demonstrated that both men and women reduced alcohol consumption after receiving a brief intervention.We found moderate-quality evidence that brief alcohol interventions have little impact on frequency of binges per week (MD -0.08, 95% CI -0.14 to -0.02; 15 studies, 6946 participants); drinking days per week (MD -0.13, 95% CI -0.23 to -0.04; 11 studies, 5469 participants); or drinking intensity (-0.2 g/drinking day, 95% CI -3.1 to 2.7; 10 studies, 3128 participants).We found moderate-quality evidence of little difference in quantity of alcohol consumed when extended and no or minimal interventions were compared (-14 g/week, 95% CI -37 to 9; 6 studies, 1296 participants). There was little difference in binges per week (-0.08, 95% CI -0.28 to 0.12; 2 studies, 456 participants; moderate-quality evidence) or difference in days drinking per week (-0.45, 95% CI -0.81 to -0.09; 2 studies, 319 participants; moderate-quality evidence). Extended versus no or minimal intervention provided little impact on drinking intensity (9 g/drinking day, 95% CI -26 to 9; 1 study, 158 participants; low-quality evidence).Extended intervention had no greater impact than brief intervention on alcohol consumption, although findings were imprecise (MD 2 g/week, 95% CI -42 to 45; 3 studies, 552 participants; low-quality evidence). Numbers of binges were not reported for this comparison, but one trial suggested a possible drop in days drinking per week (-0.5, 95% CI -1.2 to 0.2; 147 participants; low-quality evidence). Results from this trial also suggested very little impact on drinking intensity (-1.7 g/drinking day, 95% CI -18.9 to 15.5; 147 participants; very low-quality evidence).Only five studies reported adverse effects (very low-quality evidence). No participants experienced any adverse effects in two studies; one study reported that the intervention increased binge drinking for women and two studies reported adverse events related to driving outcomes but concluded they were equivalent in both study arms.Sources of funding were reported by 67 studies (87%). With two exceptions, studies were funded by government institutes, research bodies or charitable foundations. One study was partly funded by a pharmaceutical company and a brewers association, another by a company developing diagnostic testing equipment. AUTHORS' CONCLUSIONS: We found moderate-quality evidence that brief interventions can reduce alcohol consumption in hazardous and harmful drinkers compared to minimal or no intervention. Longer counselling duration probably has little additional effect. Future studies should focus on identifying the components of interventions which are most closely associated with effectiveness.
Importance: Cerebral palsy describes the most common physical disability in childhood and occurs in 1 in 500 live births. Historically, the diagnosis has been made between age 12 and 24 months but now can be made before 6 months' corrected age. Objectives: To systematically review best available evidence for early, accurate diagnosis of cerebral palsy and to summarize best available evidence about cerebral palsy-specific early intervention that should follow early diagnosis to optimize neuroplasticity and function. Evidence Review: This study systematically searched the literature about early diagnosis of cerebral palsy in MEDLINE (1956-2016), EMBASE (1980-2016), CINAHL (1983-2016), and the Cochrane Library (1988-2016) and by hand searching. Search terms included cerebral palsy, diagnosis, detection, prediction, identification, predictive validity, accuracy, sensitivity, and specificity. The study included systematic reviews with or without meta-analyses, criteria of diagnostic accuracy, and evidence-based clinical guidelines. Findings are reported according to the PRISMA statement, and recommendations are reported according to the Appraisal of Guidelines, Research and Evaluation (AGREE) II instrument. Findings: Six systematic reviews and 2 evidence-based clinical guidelines met inclusion criteria. All included articles had high methodological Quality Assessment of Diagnostic Accuracy Studies (QUADAS) ratings. In infants, clinical signs and symptoms of cerebral palsy emerge and evolve before age 2 years; therefore, a combination of standardized tools should be used to predict risk in conjunction with clinical history. Before 5 months' corrected age, the most predictive tools for detecting risk are term-age magnetic resonance imaging (86%-89% sensitivity), the Prechtl Qualitative Assessment of General Movements (98% sensitivity), and the Hammersmith Infant Neurological Examination (90% sensitivity). After 5 months' corrected age, the most predictive tools for detecting risk are magnetic resonance imaging (86%-89% sensitivity) (where safe and feasible), the Hammersmith Infant Neurological Examination (90% sensitivity), and the Developmental Assessment of Young Children (83% C index). Topography and severity of cerebral palsy are more difficult to ascertain in infancy, and magnetic resonance imaging and the Hammersmith Infant Neurological Examination may be helpful in assisting clinical decisions. In high-income countries, 2 in 3 individuals with cerebral palsy will walk, 3 in 4 will talk, and 1 in 2 will have normal intelligence. Conclusions and Relevance: Early diagnosis begins with a medical history and involves using neuroimaging, standardized neurological, and standardized motor assessments that indicate congruent abnormal findings indicative of cerebral palsy. Clinicians should understand the importance of prompt referral to diagnostic-specific early intervention to optimize infant motor and cognitive plasticity, prevent secondary complications, and enhance caregiver well-being.
Bipolar disorder is a recurrent disorder that affects more than 1% of the world population and usually has its onset during youth. Its chronic course is associated with high rates of morbidity and mortality, making bipolar disorder one of the main causes of disability among young and working-age people. The implementation of early intervention strategies may help to change the outcome of the illness and avert potentially irreversible harm to patients with bipolar disorder, as early phases may be more responsive to treatment and may need less aggressive therapies. Early intervention in bipolar disorder is gaining momentum. Current evidence emerging from longitudinal studies indicates that parental early-onset bipolar disorder is the most consistent risk factor for bipolar disorder. Longitudinal studies also indicate that a full-blown manic episode is often preceded by a variety of prodromal symptoms, particularly subsyndromal manic symptoms, therefore supporting the existence of an at-risk state in bipolar disorder that could be targeted through early intervention. There are also identifiable risk factors that influence the course of bipolar disorder, some of them potentially modifiable. Valid biomarkers or diagnosis tools to help clinicians identify individuals at high risk of conversion to bipolar disorder are still lacking, although there are some promising early results. Pending more solid evidence on the best treatment strategy in early phases of bipolar disorder, physicians should carefully weigh the risks and benefits of each intervention. Further studies will provide the evidence needed to finish shaping the concept of early intervention. AJP AT 175 Remembering Our Past As We Envision Our Future April 1925: Interpretations of Manic-Depressive Phases Earl Bond and G.E. Partridge reviewed a number of patients with manic-depressive illness in search of a unifying endo-psychic conflict. They concluded that understanding either phase of illness was "elusive" and "tantalizing beyond reach." (Am J Psychiatry 1925: 81: 643-662 ).
Diagnosis in psychiatry increasingly struggles to fulfil its key purposes, namely, to guide treatment and to predict outcome. The clinical staging model, widely used in clinical medicine yet virtually ignored in psychiatry, is proposed as a more refined form of diagnosis which could restore the utility of diagnosis, promote early intervention and also make more sense of the confusing array of biological research findings in psychiatry by organizing data into a coherent clinicopathological framework. A selective review of key papers in clinical medicine and psychiatry which describe clinical and clinicopathological staging, and a range of related issues. Clinical staging has immediate potential to improve the logic and timing of interventions in psychiatry just as it does in many complex and potentially serious medical disorders. Interventions could be evaluated in terms of their ability to prevent or delay progression from earlier to later stages of disorder, and they could be selected on clear-cut risk/benefit criteria. Biological variables and a range of candidate risk factors could be studied within and across stages, and their role, specificity and centrality in risk, onset and progression of disorder could be greatly clarified. A clinicopathological framework could be progressively constructed. Clinical staging with a restructure across and within diagnostic boundaries with the explicit operationalization of criteria for extent and progression of disorder should be actively explored in psychiatry as a heuristic strategy for the development and evaluation of earlier, safer, and more effective clinical interventions, and for clarifying the biological basis of psychiatric disorders.
BACKGROUND: The accumulation of soluble and insoluble aggregated amyloid-beta (Aβ) may initiate or potentiate pathologic processes in Alzheimer's disease. Lecanemab, a humanized IgG1 monoclonal antibody that binds with high affinity to Aβ soluble protofibrils, is being tested in persons with early Alzheimer's disease. METHODS: We conducted an 18-month, multicenter, double-blind, phase 3 trial involving persons 50 to 90 years of age with early Alzheimer's disease (mild cognitive impairment or mild dementia due to Alzheimer's disease) with evidence of amyloid on positron-emission tomography (PET) or by cerebrospinal fluid testing. Participants were randomly assigned in a 1:1 ratio to receive intravenous lecanemab (10 mg per kilogram of body weight every 2 weeks) or placebo. The primary end point was the change from baseline at 18 months in the score on the Clinical Dementia Rating-Sum of Boxes (CDR-SB; range, 0 to 18, with higher scores indicating greater impairment). Key secondary end points were the change in amyloid burden on PET, the score on the 14-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog14; range, 0 to 90; higher scores indicate greater impairment), the Alzheimer's Disease Composite Score (ADCOMS; range, 0 to 1.97; higher scores indicate greater impairment), and the score on the Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL; range, 0 to 53; lower scores indicate greater impairment). RESULTS: A total of 1795 participants were enrolled, with 898 assigned to receive lecanemab and 897 to receive placebo. The mean CDR-SB score at baseline was approximately 3.2 in both groups. The adjusted least-squares mean change from baseline at 18 months was 1.21 with lecanemab and 1.66 with placebo (difference, -0.45; 95% confidence interval [CI], -0.67 to -0.23; P<0.001). In a substudy involving 698 participants, there were greater reductions in brain amyloid burden with lecanemab than with placebo (difference, -59.1 centiloids; 95% CI, -62.6 to -55.6). Other mean differences between the two groups in the change from baseline favoring lecanemab were as follows: for the ADAS-cog14 score, -1.44 (95% CI, -2.27 to -0.61; P<0.001); for the ADCOMS, -0.050 (95% CI, -0.074 to -0.027; P<0.001); and for the ADCS-MCI-ADL score, 2.0 (95% CI, 1.2 to 2.8; P<0.001). Lecanemab resulted in infusion-related reactions in 26.4% of the participants and amyloid-related imaging abnormalities with edema or effusions in 12.6%. CONCLUSIONS: Lecanemab reduced markers of amyloid in early Alzheimer's disease and resulted in moderately less decline on measures of cognition and function than placebo at 18 months but was associated with adverse events. Longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer's disease. (Funded by Eisai and Biogen; Clarity AD ClinicalTrials.gov number, NCT03887455.).
BACKGROUND: The use of positive psychological interventions may be considered as a complementary strategy in mental health promotion and treatment. The present article constitutes a meta-analytical study of the effectiveness of positive psychology interventions for the general public and for individuals with specific psychosocial problems. METHODS: We conducted a systematic literature search using PubMed, PsychInfo, the Cochrane register, and manual searches. Forty articles, describing 39 studies, totaling 6,139 participants, met the criteria for inclusion. The outcome measures used were subjective well-being, psychological well-being and depression. Positive psychology interventions included self-help interventions, group training and individual therapy. RESULTS: The standardized mean difference was 0.34 for subjective well-being, 0.20 for psychological well-being and 0.23 for depression indicating small effects for positive psychology interventions. At follow-up from three to six months, effect sizes are small, but still significant for subjective well-being and psychological well-being, indicating that effects are fairly sustainable. Heterogeneity was rather high, due to the wide diversity of the studies included. Several variables moderated the impact on depression: Interventions were more effective if they were of longer duration, if recruitment was conducted via referral or hospital, if interventions were delivered to people with certain psychosocial problems and on an individual basis, and if the study design was of low quality. Moreover, indications for publication bias were found, and the quality of the studies varied considerably. CONCLUSIONS: The results of this meta-analysis show that positive psychology interventions can be effective in the enhancement of subjective well-being and psychological well-being, as well as in helping to reduce depressive symptoms. Additional high-quality peer-reviewed studies in diverse (clinical) populations are needed to strengthen the evidence-base for positive psychology interventions.
Aging is characterized by systemic chronic inflammation, which is accompanied by cellular senescence, immunosenescence, organ dysfunction, and age-related diseases. Given the multidimensional complexity of aging, there is an urgent need for a systematic organization of inflammaging through dimensionality reduction. Factors secreted by senescent cells, known as the senescence-associated secretory phenotype (SASP), promote chronic inflammation and can induce senescence in normal cells. At the same time, chronic inflammation accelerates the senescence of immune cells, resulting in weakened immune function and an inability to clear senescent cells and inflammatory factors, which creates a vicious cycle of inflammation and senescence. Persistently elevated inflammation levels in organs such as the bone marrow, liver, and lungs cannot be eliminated in time, leading to organ damage and aging-related diseases. Therefore, inflammation has been recognized as an endogenous factor in aging, and the elimination of inflammation could be a potential strategy for anti-aging. Here we discuss inflammaging at the molecular, cellular, organ, and disease levels, and review current aging models, the implications of cutting-edge single cell technologies, as well as anti-aging strategies. Since preventing and alleviating aging-related diseases and improving the overall quality of life are the ultimate goals of aging research, our review highlights the critical features and potential mechanisms of inflammation and aging, along with the latest developments and future directions in aging research, providing a theoretical foundation for novel and practical anti-aging strategies.
As the COVID-19 pandemic has largely increased the utilization of telehealth, mobile mental health technologies - such as smartphone apps, vir-tual reality, chatbots, and social media - have also gained attention. These digital health technologies offer the potential of accessible and scalable interventions that can augment traditional care. In this paper, we provide a comprehensive update on the overall field of digital psychiatry, covering three areas. First, we outline the relevance of recent technological advances to mental health research and care, by detailing how smartphones, social media, artificial intelligence and virtual reality present new opportunities for "digital phenotyping" and remote intervention. Second, we review the current evidence for the use of these new technological approaches across different mental health contexts, covering their emerging efficacy in self-management of psychological well-being and early intervention, along with more nascent research supporting their use in clinical management of long-term psychiatric conditions - including major depression; anxiety, bipolar and psychotic disorders; and eating and substance use disorders - as well as in child and adolescent mental health care. Third, we discuss the most pressing challenges and opportunities towards real-world implementation, using the Integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework to explain how the innovations themselves, the recipients of these innovations, and the context surrounding innovations all must be considered to facilitate their adoption and use in mental health care systems. We conclude that the new technological capabilities of smartphones, artificial intelligence, social media and virtual reality are already changing mental health care in unforeseen and exciting ways, each accompanied by an early but promising evidence base. We point out that further efforts towards strengthening implementation are needed, and detail the key issues at the patient, provider and policy levels which must now be addressed for digital health technologies to truly improve mental health research and treatment in the future.
PURPOSE OF REVIEW: In this review, we discuss feasibility, content, and where possible efficacy of ecological momentary interventions (EMIs) in psychiatry. EMIs adopt mobile devices, such as personal digital assistants or smartphones, for the delivery of treatments in the daily life of patients. We will discuss EMIs in the field of schizophrenia, bipolar disorder and major depression disorder, as well as one generic, transdiagnostic EMI. RECENT FINDINGS: The few studies that are available all underscore feasibility and acceptability of mobile health approaches in patients with severe mental illness. In terms of content, there is a huge variety in approaches ranging from a mixture of face-to-face contacts augmented with EMI components to a fully automated EMI. With regard to efficacy, only two randomized clinical trials have been conducted, supporting the efficacy of EMIs in mental health. Evidence seems to point toward greater efficacy when EMI is integrated with real-life assessment using experience sampling methodology, preferentially tailoring the intervention toward the specific needs of the individual as well as toward those moments when intervention is needed. SUMMARY: The review demonstrates that mobile health may be an important asset to the mental health field but underscores that it still is in its very early ages. In the discussion, we point toward ways of improving EMIs for severe mental illness, changing our perspective from testing feasibility to testing efficacy and ultimately implementing EMIs in routine mental health services.
Mindfulness interventions aim to foster greater attention to and awareness of present moment experience. There has been a dramatic increase in randomized controlled trials (RCTs) of mindfulness interventions over the past two decades. This article evaluates the growing evidence of mindfulness intervention RCTs by reviewing and discussing (a) the effects of mindfulness interventions on health, cognitive, affective, and interpersonal outcomes; (b) evidence-based applications of mindfulness interventions to new settings and populations (e.g., the workplace, military, schools); (c) psychological and neurobiological mechanisms of mindfulness interventions; (d) mindfulness intervention dosing considerations; and (e) potential risks of mindfulness interventions. Methodologically rigorous RCTs have demonstrated that mindfulness interventions improve outcomes in multiple domains (e.g., chronic pain, depression relapse, addiction). Discussion focuses on opportunities and challenges for mindfulness intervention research and on community applications.
Importance: The value of early intervention in psychosis and allocation of public resources has long been debated because outcomes in people with schizophrenia spectrum disorders have remained suboptimal. Objective: To compare early intervention services (EIS) with treatment as usual (TAU) for early-phase psychosis. Data Sources: Systematic literature search of PubMed, PsycINFO, EMBASE, and ClinicalTrials.gov without language restrictions through June 6, 2017. Study Selection: Randomized trials comparing EIS vs TAU in first-episode psychosis or early-phase schizophrenia spectrum disorders. Data Extraction and Synthesis: This systematic review was conducted according to PRISMA guidelines. Three independent investigators extracted data for a random-effects meta-analysis and prespecified subgroup and meta-regression analyses. Main Outcomes and Measures: The coprimary outcomes were all-cause treatment discontinuation and at least 1 psychiatric hospitalization during the treatment period. Results: Across 10 randomized clinical trials (mean [SD] trial duration, 16.2 [7.4] months; range, 9-24 months) among 2176 patients (mean [SD] age, 27.5 [4.6] years; 1355 [62.3%] male), EIS was associated with better outcomes than TAU at the end of treatment for all 13 meta-analyzable outcomes. These outcomes included the following: all-cause treatment discontinuation (risk ratio [RR], 0.70; 95% CI, 0.61-0.80; P < .001), at least 1 psychiatric hospitalization (RR, 0.74; 95% CI, 0.61-0.90; P = .003), involvement in school or work (RR, 1.13; 95% CI, 1.03-1.24; P = .01), total symptom severity (standardized mean difference [SMD], -0.32; 95% CI, -0.47 to -0.17; P < .001), positive symptom severity (SMD, -0.22; 95% CI, -0.32 to -0.11; P < .001), and negative symptom severity (SMD, -0.28; 95% CI, -0.42 to -0.14; P < .001). Superiority of EIS regarding all outcomes was evident at 6, 9 to 12, and 18 to 24 months of treatment (except for general symptom severity and depressive symptom severity at 18-24 months). Conclusions and Relevance: In early-phase psychosis, EIS are superior to TAU across all meta-analyzable outcomes. These results support the need for funding and use of EIS in patients with early-phase psychosis.
Diagnosis in psychiatry continues to struggle to fulfil its key purposes, namely to guide treatment and to predict outcome. A clinical staging model, widely used in clinical medicine, could improve the utility of diagnosis in psychiatry, especially in young people with emerging disorders. Clinical staging has immediate potential to improve the logic and timing of interventions in psychiatry, as it does in many complex and potentially serious medical disorders. Interventions could be evaluated in terms of their ability to prevent or delay progression from earlier to later stages of a disorder, and selected by consumers and clinicians on the basis of clear-cut risk-benefit criteria. This would ensure that, as treatments are offered earlier, they remain safe, acceptable and affordable, and potentially more effective. Biological variables and a range of candidate risk and protective factors could be studied within and across stages, and their role, specificity and centrality in risk, onset and progression of disorders clarified. In this way, a clinicopathological framework could be progressively constructed. Clinical staging, with restructuring across and within diagnostic boundaries and explicit operational criteria for extent and progression of disorder, should be actively explored in psychiatry as a heuristic strategy for developing and evaluating earlier, safer, and more effective clinical interventions, and for clarifying the biological basis of psychiatric disorders. Young people with emerging mental and substance use disorders could be the main beneficiaries.
Due to the progressive aging of the population, Alzheimer's disease (AD) is becoming a healthcare burden of epidemic proportions for which there is currently no cure. Disappointing results from clinical trials performed in mild-moderate AD dementia combined with clear epidemiological evidence on AD risk factors are contributing to the development of primary prevention initiatives. In addition, the characterization of the long asymptomatic stage of AD is allowing the development of intervention studies and secondary prevention programmes on asymptomatic at-risk individuals, before substantial irreversible neuronal dysfunction and loss have occurred, an approach that emerges as highly relevant.In this manuscript, we review current strategies for AD prevention, from primary prevention strategies based on identifying risk factors and risk reduction, to secondary prevention initiatives based on the early detection of the pathophysiological hallmarks and intervention at the preclinical stage of the disease. Firstly, we summarize the evidence on several AD risk factors, which are the rationale for the establishment of primary prevention programmes as well as revising current primary prevention strategies. Secondly, we review the development of public-private partnerships for disease prevention that aim to characterize the AD continuum as well as serving as platforms for secondary prevention trials. Finally, we summarize currently ongoing clinical trials recruiting participants with preclinical AD or a higher risk for the onset of AD-related cognitive impairment.The growing body of research on the risk factors for AD and its preclinical stage is favouring the development of AD prevention programmes that, by delaying the onset of Alzheimer's dementia for only a few years, would have a huge impact on public health.
BACKGROUND: Early intervention services for psychosis aim to detect emergent symptoms, reduce the duration of untreated psychosis, and improve access to effective treatments. AIMS: To evaluate the effectiveness of early intervention services, cognitive-behavioural therapy (CBT) and family intervention in early psychosis. METHOD: Systematic review and meta-analysis of randomised controlled trials of early intervention services, CBT and family intervention for people with early psychosis. RESULTS: Early intervention services reduced hospital admission, relapse rates and symptom severity, and improved access to and engagement with treatment. Used alone, family intervention reduced relapse and hospital admission rates, whereas CBT reduced the severity of symptoms with little impact on relapse or hospital admission. CONCLUSIONS: For people with early psychosis, early intervention services appear to have clinically important benefits over standard care. Including CBT and family intervention within the service may contribute to improved outcomes in this critical period. The longer-term benefits of this approach and its component treatments for people with early and established psychosis need further research.
Personalized medicine is rapidly becoming a reality in today's physical medicine. However, as yet this is largely an aspirational goal in psychiatry, despite significant advances in our understanding of the biochemical, genetic and neurobiological processes underlying major mental disorders. Preventive medicine relies on the availability of predictive tools; in psychiatry we still largely lack these. Furthermore, our current diagnostic systems, with their focus on well-established, largely chronic illness, do not support a pre-emptive, let alone a preventive, approach, since it is during the early stages of a disorder that interventions have the potential to offer the greatest benefit. Here, we present a clinical staging model for severe mental disorders and discuss examples of biological markers that have already undergone some systematic evaluation and that could be integrated into such a framework. The advantage of this model is that it explicitly considers the evolution of psychopathology during the development of a mental illness and emphasizes that progression of illness is by no means inevitable, but can be altered by providing appropriate interventions that target individual modifiable risk and protective factors. The specific goals of therapeutic intervention are therefore broadened to include the prevention of illness onset or progression, and to minimize the risk of harm associated with more complex treatment regimens. The staging model also facilitates the integration of new data on the biological, social and environmental factors that influence mental illness into our clinical and diagnostic infrastructure, which will provide a major step forward in the development of a truly pre-emptive psychiatry.
BACKGROUND: Synthesis of multiple randomized controlled trials (RCTs) in a systematic review can summarize the effects of individual outcomes and provide numerical answers about the effectiveness of interventions. Filtering of searches is time consuming, and no single method fulfills the principal requirements of speed with accuracy. Automation of systematic reviews is driven by a necessity to expedite the availability of current best evidence for policy and clinical decision-making. We developed Rayyan ( http://rayyan.qcri.org ), a free web and mobile app, that helps expedite the initial screening of abstracts and titles using a process of semi-automation while incorporating a high level of usability. For the beta testing phase, we used two published Cochrane reviews in which included studies had been selected manually. Their searches, with 1030 records and 273 records, were uploaded to Rayyan. Different features of Rayyan were tested using these two reviews. We also conducted a survey of Rayyan's users and collected feedback through a built-in feature. RESULTS: Pilot testing of Rayyan focused on usability, accuracy against manual methods, and the added value of the prediction feature. The "taster" review (273 records) allowed a quick overview of Rayyan for early comments on usability. The second review (1030 records) required several iterations to identify the previously identified 11 trials. The "suggestions" and "hints," based on the "prediction model," appeared as testing progressed beyond five included studies. Post rollout user experiences and a reflexive response by the developers enabled real-time modifications and improvements. The survey respondents reported 40% average time savings when using Rayyan compared to others tools, with 34% of the respondents reporting more than 50% time savings. In addition, around 75% of the respondents mentioned that screening and labeling studies as well as collaborating on reviews to be the two most important features of Rayyan. As of November 2016, Rayyan users exceed 2000 from over 60 countries conducting hundreds of reviews totaling more than 1.6M citations. Feedback from users, obtained mostly through the app web site and a recent survey, has highlighted the ease in exploration of searches, the time saved, and simplicity in sharing and comparing include-exclude decisions. The strongest features of the app, identified and reported in user feedback, were its ability to help in screening and collaboration as well as the time savings it affords to users. CONCLUSIONS: Rayyan is responsive and intuitive in use with significant potential to lighten the load of reviewers.