Elsevier

Schizophrenia Research

Volume 51, Issue 1, 1 August 2001, Pages 17-29
Schizophrenia Research

Ethics and early intervention in psychosis: keeping up the pace and staying in step

https://doi.org/10.1016/S0920-9964(01)00235-3Get rights and content

Abstract

The intense clinical and research interest in early psychosis in recent years has highlighted a range of ethical issues which need to be considered carefully. Our perspective is based on 16 years of clinical and research experience with young people at this phase of illness as well as the research contributions of many others. We discuss the ethical dilemmas in relation to the three key foci, which make up the early psychosis paradigm. These are the pre-psychotic or prodromal phase, the period of untreated psychosis and the first psychotic episode and the critical period of recovery, which follows this. Most attention is devoted to the pre-psychotic period, however ethical considerations related to research in the other two clinical foci are briefly covered as well. Our contention is that the ethical issues are essentially identical to those arising in early intervention research in mainstream medicine. This has been concealed by inconsistency and emotion, which has great potential to confuse, politicize and derail rational debate. The legacy of the isolation of psychiatry from medicine and consequent prejudice and stigma in the professional as well as the public mind seems to be fuelling a tendency in some societies to view psychiatric research as qualitatively different from other medical research. Sound clinical research data should be allowed to illuminate the options for potential consumers across all phases of illness. The alternative is research paralysis, which would force clinical practice to expand blindly without an evidence base.

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

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