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Original Research

Intervention in Individuals at Ultra High Risk for Psychosis: A Review and Future Directions

Patrick D. McGorry, PhD; Barnaby Nelson, PhD; G. Paul Amminger, MD; Andreas Bechdolf, MD; Shona M. Francey, PhD; Gregor Berger, MD; Anita Riecher-Rössler, MD; Joachim Klosterkötter, MD; Stephan Ruhrmann, MD; Frauke Schultze-Lutter, PhD; Merete Nordentoft, PhD; Ian Hickie, MD, FRANZCP; Philip McGuire, MD; Michael Berk, PhD; Eric Y. H. Chen, MD, MRCPscyh, FHKAM; Matcheri S. Keshavan, MD; and Alison R. Yung, MD

Published: June 30, 2009

Article Abstract

Objective: Over the last 15 years, a focus on early intervention in psychotic disorders has emerged. Initially, the early psychosis movement focused on timely recognition and phase-specific treatment of first-episode psychosis. However, early psychosis researchers suspected that pushing the point of intervention even further back to the prodromal phase of psychotic disorders may result in even better outcomes. This article reviews intervention research in the ultra-high-risk phase of psychotic disorders.

Data sources: A literature search of intervention trials with ultra-high-risk cohorts published after 1980 was conducted on PubMed with the search terms prodrome and intervention.

Study selection: All published intervention trials with ultra-high-risk cohorts.

Data synthesis: The first generation of intervention trials indicated that both pharmacologic and psychological intervention strategies may be of value in terms of symptom reduction and delay or prevention of onset of threshold psychotic disorder.

Conclusions: Further controlled intervention trials with larger sample sizes are required in order to confirm and extend these findings. We argue that the clinical staging model provides a framework for the rationale and design of such studies, with simpler, safer, and more benign interventions being better candidates for first-line treatment, while more complex and potentially harmful treatments should be reserved for those cases in which response has failed to occur. Recent evidence indicates that neuroprotective agents, such as essential fatty acids, may be a suitable form of intervention for the ultra-high-risk phase of psychotic disorders, with a positive risk-benefit balance. Ethical aspects have become more salient given the recently observed declining transition rate in ultra-high-risk samples. We outline the key questions for the next generation of ultra-high-risk intervention trials.


Submitted: June 16, 2008; accepted September 17, 2008.

Online ahead of print: June 30, 2009.

Corresponding author: Barnaby Nelson, PhD, Orygen Research Centre, 35 Poplar Rd (Locked Bag 10), Parkville, Victoria 3052, Australia (

Volume: 70

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