Ethics and early intervention in psychosis: keeping up the pace and staying in step☆
Introduction
Clinical and research interest in early psychosis is growing rapidly, and strategies for preventive intervention are now more realistic and popular worldwide (Edwards et al., 2000). After decades of unremitting pessimism, particularly in schizophrenia and non-affective psychosis, a range of forces has combined to prize open the door sufficiently to allow preventive models to influence research and clinical care. Because one of the obstacles to this shift is the flawed Kraepelinian conceptual model itself (Crow, 1986, McGorry et al., 1990), it is critical to focus more broadly on early psychosis rather than schizophrenia alone (McGorry, 1995). Psychosis is a more proximal and definable target, particularly since syndromal comorbidity and flux are common in the early phases of illness in young people, and delayed and inadequate treatment is increasingly recognized in all serious mental illnesses. Our main contention is that the ethics of early intervention in psychosis are essentially the same as in mainstream healthcare, though there are some specific obstacles, mainly arising from the alienist history of psychiatry and overwhelming prejudice and distrust, towards patients, clinicians and researchers, which still contaminate rational debate. Since true primary prevention remains out of reach, there are essentially three preventive foci, namely pre-psychotic intervention, early detection and phase-specific intensive treatment during the critical period after diagnosis of first episode psychosis (FEP). These foci will be used as a framework for a consideration of the ethical issues.
The first focus involves the pre-psychotic phase, when most psychosocial impairment develops but the specifics of treatment remain difficult to research and apply. This will be the main focus considered and a delineation of the key ethical issues linked to review of clinical experience and research data will be presented. Secondly, while the extent of prepsychotic deterioration may mean that the total duration of untreated illness (DUI) may ultimately prove more critical, the duration of untreated psychosis (DUP) is a more realistic immediate target for early detection and intervention. Although DUP has not yet been conclusively demonstrated to be a malleable causal risk factor influencing outcome, early detection and engagement in treatment are well justified on clinical grounds (Lieberman and Fenton, 2000), and consequently are being systematically implemented in many countries (Edwards et al., 2000). Once frank psychosis has become established, most would argue that it makes no sense to withhold antipsychotic and psychosocial treatments, especially since the former has become increasingly safe and effective. Yet skepticism persists as to whether early detection can influence the longer-term course of illness. What research designs could be employed to address this skepticism in an ethical manner? Where is the onus of proof?
Finally, FEP is comparatively more treatment responsive than multi-episode psychosis, and intensive phase-specific treatment appears to result in short term improvements in outcome and cost-effectiveness. It is probable that good adherence to low dose atypical antipsychotic medications and more intensive and skilled psychosocial treatment in this critical period of the illness (the first episode and the ensuing 2–5 years) will reduce the mortality, morbidity, costs of treatment, and ultimately the overall prevalence of psychotic disorders (Birchwood et al., 1997, Birchwood et al., 2000). This is logical, yet still unproven. While the majority of patients will probably benefit from longer term treatment, there are still finite risks associated with this, and a significant subset will turn out not to have needed it, just as in the prodromal scenario. The twin parameters of Number Needed to Treat (NNT) and Number Needed to Harm (NNH) (Cook and Sackett, 1995), which can be derived from randomized controlled trial (RCT) data and are routinely utilized in the Cochrane reviews, are helpful in appreciating this unresolved dilemma. Despite the surprising lack of this essential data, some have taken the opposite stance to that adopted in relation to the prodromal phase, arguing that studies designed to compare different intensities and durations of core treatments are unethical. How can ethical research be designed to examine whether the intensity, duration and ‘grip’ of intervention especially but not solely drug therapies, during the early years after a first episode, influences outcome, and for which patients?
Section snippets
A clinical research strategy in early psychosis
Before considering the three preventive foci identified, we explicate our evolving approach, which commenced in 1984 in Melbourne with the establishment of a specialist stand-alone in-patient unit for the assessment and treatment of young people with FEP (McGorry, 1985, Copolov et al., 1989). We adopted the clinician-researcher model described by Schooler and Baker (1999) and this has served us well in relation to ethical issues over a prolonged period notwithstanding the inherent tensions. Our
Rationale and research
The sense of having arrived on the scene too late to really help the patient is prominent in chronic schizophrenia (McGlashan and Johanssen, 1996). It is an unexpectedly common experience too in FEP, partly because long delays are not uncommon even after clearcut psychosis has emerged (Loebel et al., 1992, McGlashan, 1999), but also because even before this there is usually an even longer period of more subtle symptomatology which erodes the developmental achievements and potential of the
Rationale and research
The currently accepted threshold for treatment with antipsychotic medication is at the first clear and sustained emergence of psychotic features. Despite this, for a substantial proportion of people, such treatment is delayed, often for very prolonged periods (McGlashan, 1999). For others, especially in the developing world (Padmavathi et al., 1998), treatment is never accessed. DUP, as a marker of delay in delivering effective specific treatment, is a potentially important variable in
The recovery phase or critical period after the first psychotic episode
Once the first episode of psychosis is treated as effectively as possible, a minority of patients will have treatment-resistant symptoms and a majority will achieve syndromal remission, though functional recovery is often more elusive in the short term. What are the ethical controversies in this phase of the early psychosis spectrum? A prevailing opinion, is that it may be unethical to consider studies of different durations of antipsychotic treatment post-first-episode, even in the fully
Conclusions
A potential obstacle to progress stems from inconsistencies in logic across phases of illness and the threat of censorship of particular research foci. This seems to be driven at least partly by emotional and political determinants arising from celebrated cases, legal pressures and a divided consumer voice. We sense that such pressures have already censored research activity in some places in key aspects of schizophrenia treatment, and get the impression that something similar is at risk of
References (72)
- et al.
Negative labelling of individuals with first episode schizophrenia: the effect of premorbid functioning
Schizophr. Res.
(1996) - et al.
Does treatment delay in first-episode psychosis really mater?
Schizophr. Res.
(2000) - et al.
Two-year outcome in first-episode psychosis treated according to an integrated model. Is immediate neuroleptisation always needed?
Eur. Psychiatry
(2000) - et al.
Neurochemical sensitization in the pathophysiology of schizophrenia: deficits and dysfunction in neuronal regulation and plasticity
Neuropsychopharmacology
(1997) Duration of untreated psychosis in first-episode schizophrenia: marker or determinant of course?
Biol. Psychiatry
(1999)- et al.
Functional psychosis: the case for a loosening of associations
Schizophr. Res.
(1990) - et al.
A randomised controlled trial of interventions in the pre-psychotic phase of psychotic disorders
Schizophr. Res.
(2000) - et al.
Treatment of nonpsychotic relatives of patients with schizophrenia: four case studies
Biol. Psychiatry
(1999) - et al.
Strauss (1969) revisited: A psychosis continuum in the general population?
Schizophr. Res.
(2000) - et al.
Prediction of duration of psychosis before first admission
Eur. Psychiatry
(1998)
Missing the boat: competence and consent in psychiatric research
Am. J. Psychiatry
The Macarther Competence Assessment Tool — Clinical Research Manual
Antipsychotic drug treatment: recent advances
Curr. Opin. Psychiatry
West London first-episode study of schizophrenia. Clinical correlates of duration of untreated psychosis
Br. J. Psychiatry
Early intervention in schizophrenia
Br. J. Psychiatry
Duration of untreated psychosis and 12-month outcome in first-episode psychosis: the impact of treatment approach
Acta Psychiatr. Scand.
The rationale and ethics of medication-free research in schizophrenia
Arch. Gen. Psychiatry
The number needed to treat: a clinically useful measure of treatment effect
Br. Med. J.
Origins and establishment of the Schizophrenia Research Program at Royal Park Psychiatric Hospital
Aust. N Z. J. Psychiatry
Characterization and treatment of the schizophrenia prodrome: Results of a three-year prospective study
Schizophr. Res.
Is there an association between duration of untreated psychosis and 24-month clinical outcome in a first-admission series?
Am. J. Psychiatry
The continuum of psychosis and its implications for the structure of the gene
Br. J. Psychiatry
The Northwick Park study of first episodes of schizophrenia. II. A randomized controlled trial of prophylactic neuroleptic treatment
Br. J. Psychiatry
Causes and consequences of duration of untreated psychosis in schizophrenia
Br. J. Psychiatry
The Sociology of Mental Disorders
Prodromes and precursors: Epidemiologic data for primary prevention of disorders with slow onset
Am. J. Psychiatry
Early psychosis prevention and intervention: evolution of a comprehensive community-based specialised service
Behaviour Change
Models of early intervention in psychosis: an analysis of service approaches
Early intervention for first episode of schizophrenia: a preliminary exploration
Psychiatry
Threats to validity in outcome studies of early intervention in schizophrenia
Schizophr. Res.
Untreated initial psychosis: its relation to quality of life and symptom remission in first-episode schizophrenia
Am. J. Psychiatry
Prevalence and incidence of schizophrenia spectrum disorders: implications for prevention
Aust. NZ J. Psychiatry
Strategies for reducing duration of untreated psychosis
Schizophr. Res.
Cited by (133)
The benefit of foresight? An ethical evaluation of predictive testing for psychosis in clinical practice
2020, NeuroImage: ClinicalCitation Excerpt :Decision-making capacity for predictive testing requires careful consideration for a number of reasons. Firstly, those at high risk for psychosis can have significant levels of comorbid psychiatric disorders, intellectual disabilities, and subthreshold psychotic symptoms, all of which are potentially (though not inevitably) capacity impairing (Mittal et al., 2015; Heinssen et al., 2001; Corcoran, 2016; Lawrie et al., 2019; McGorry et al., 2001). Of note, provision of extra time and explanation has been shown to facilitate capacity in those with established schizophrenia, leveling off the disparity with unaffected controls (Heinssen et al., 2001; Morris and Heinssen, 2014; McGorry et al., 2001).
The Prodrome of Psychotic Disorders: Identification, Prediction, and Preventive Treatment
2020, Child and Adolescent Psychiatric Clinics of North AmericaCitation Excerpt :Much of the disability associated with psychotic disorders, particularly schizophrenia, develops long before the onset of frank psychosis and is difficult to reverse even if the first psychotic episode is successfully treated.9 Within the context of the early intervention paradigm, it was suspected that pushing the point of intervention even further back from the first episode of psychosis to the prodromal phase may result in even better outcomes.10–13 The rationale was that intervening during this phase may ameliorate, delay, or even prevent onset of fully fledged disorder,7 thereby reducing the burden of disability, prevalence, and possibly even the incidence of psychotic disorders.
Stigma related to labels and symptoms in individuals at clinical high-risk for psychosis
2015, Schizophrenia ResearchPediatric Clinical Trial Activity for Antipsychotics and the Sharing of Results: A Complex Ethical Landscape
2015, The Science and Ethics of Antipsychotic Use in ChildrenMy child's future mental health: Carer's engagement with risk identification in an intervention study for youth with at-risk mental states
2022, Early Intervention in PsychiatryThe neurobiology of suicide in psychosis: A systematic review
2020, Journal of Psychopharmacology
- ☆
A review based on experience at the Early Psychosis Prevention and Intervention Centre (EPPIC) and the Personal Assessment and Crisis Evaluation (PACE) clinic.