Early intervention in psychosis: concepts, evidence and future directions

Patrick D. McGorry, Eóin Killackey, Alison R. Yung · 2008 · 583 citationsRead the paper

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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