An evidence map of interventions across premorbid, ultra-high risk and first episode phases of psychosis

Abstract

The onset of psychotic disorders peaks in adolescence and young adulthood. Early interventions during the ultra-high risk and first episode stages of illness are increasingly emphasised given the greater opportunities for clinical and functional recovery during these early phases. As a large volume of such research now exists, there is a need to summarise the extent and distribution of research to ascertain what is, and is not yet known about the evidence-base for preventing and treating early psychotic disorders.

Methods

An ‘evidence mapping’ methodology was used to systematically search for intervention studies published post-1980 in English (participant mean age: 6–30 years). Studies were restricted to systematic reviews, meta-analyses and controlled trials. The Cochrane Central Register of Controlled Trials, PSYCHINFO, MEDLINE and EMBASE were searched. Studies were screened according to these criteria and mapped on pre-defined study characteristics, including intervention types, stage of illness and type of study.

Results

Fifty-eight controlled trials and 8 systematic reviews were identified. The majority pertained to the first episode stage of illness (n = 37), indicated prevention (n = 9) and relapse prevention (n = 9). Most studies involved biological (n = 32) or psychological (n = 17) interventions. Antipsychotic medication (n = 27) and cognitive behavioural therapy (CBT; n = 10) were the most common intervention modalities.

Conclusions

The extant research is dominated by trials examining intervention for first episode psychosis with antipsychotic medication. Biological interventions other than antipsychotics are sparse for patients with established psychotic disorders. For at-risk populations, there is a need for high-quality prevention studies of pharmaceutical treatments (e.g. neuroprotective agents) and a broad range of psychosocial interventions, including, but not limited to, CBT.

Introduction

The early intervention model for psychotic disorders, established over the last two decades (Keshavan and Schooler, 1992), has resulted in a steadily growing field of clinical practice and research aimed at improving outcomes and prognosis for patients with psychosis. There are two streams of evidence supporting the early intervention paradigm. Firstly, accumulating evidence shows that the duration of untreated psychosis (DUP) is negatively associated with the long-term symptomatic and functional outcomes in schizophrenia (Marshall et al., 2005, Perkins et al., 2005). Secondly, research indicates that cognitive functioning deteriorates steeply before psychotic symptoms fully manifest (Davidson et al., 1999, Caspi et al., 2003). Thus, interventions delivered during the early phases of illness manifestation are believed to help preserve the individual's overall functional ability by reducing DUP and/or addressing the deterioration of functioning before the occurrence of a first episode of psychosis.

The course of psychosis can be divided into three phases: premorbid, prodromal and florid psychosis (Fava and Kellner, 1993, McGorry et al., 2006), however, the premorbid and prodromal phases are often only identifiable retrospectively once a full-threshold episode has occurred (Yung et al., 2007). The premorbid phase is the period of relative normality before patients exhibit any psychotic symptoms (other symptoms may be present however, such as anxiety or depression). The prodromal phase is a period characterized by accelerating global functioning decline and the emergence of psychotic symptoms. The florid phase refers to the experience of full-scale symptoms such as delusions, hallucinations and thought disturbance. Early interventions can be delivered at any of these three stages; for example, to detect patients early through increased awareness and mental health literacy campaigns (Johannessen et al., 2005); to intervene at the prodromal phase in order to reduce the transition rate to a first episode of psychosis (McGorry et al., 2002); or to provide early interventions at the point of onset of a first episode of psychosis (McGorry et al., 1996).

A variety of early intervention approaches have been examined to various degrees internationally, targeting the prodromal phase and the first episode of psychosis. In an attempt to prospectively identify the prodromal phase of psychosis, Yung and McGorry identified features associated with the ultra-high risk (UHR) stage of developing a psychotic disorder (Yung and McGorry, 1996). These UHR criteria have since been adopted or adapted by a number of other clinical research programs internationally (e.g. McGorry et al., 2003), leading to the empirical testing of interventions that aim to prevent the transition to psychosis or to postpone the onset of the illness. Interventions in the prodromal phase have included psychological therapies targeting symptoms of anxiety and depression, along with psychosocial distress associated with the prodrome (Bechdolf et al., 2006), as well as the use of antipsychotic medication aimed at preventing the occurrence of a full-blown episode of psychosis (McGorry et al., 2002). The use of antipsychotics in the prodromal phase is still controversial, as the majority of patients meeting ultra-high risk criteria do not develop a frank psychotic episode (Yung et al., 2006). However, it is unclear whether there is enough compelling evidence on which to draw conclusions regarding the efficacy of interventions in the prodromal phase in general (Marshall and Rathbone, 2006). Interventions aimed at alleviating the symptoms in a first episode of psychosis have included psychological therapies, antipsychotic medication and integrated or specialised interventions, the latter typically involving an early intervention service delivering a combination of intensive case management, psychotherapies and antipsychotic medications.

In a developing and, at times, controversial area of research, the need to summarise the evidence-base for interventions and to identify potential gaps in knowledge is vital in order to inform best clinical practice and direct future research. The methodology of ‘evidence mapping’, developed by Katz et al. (2003), is a useful and appropriate approach to providing a comprehensive overview of early interventions in psychosis. Evidence mapping adopts a similar approach to systematic reviews, using explicit and reproducible methods, yet remains broader and less detailed (Arksey, 2003). Unlike systematic reviews, which only answer one specific clinical question (e.g., is treatment X effective for condition Y?), evidence mapping allows a concise summary of the existing literature in the broad field of interest, while simultaneously having the capability to identify gaps in the research literature (e.g., what interventions are available for condition Y?).

This paper presents an overview of the extent, range and nature of high-quality clinical research interventions for early psychosis by summarising the empirical evidence from randomised controlled trials (RCTs), controlled clinical trials (CCTs), and systematic reviews and/or meta-analyses. As a result, existing gaps in the evidence will also be identified, which will be relevant to those developing (or funding) new research agendas.