Patients at high risk for psychosis pose a clinical dilemma

The concept of a clinical high risk syndrome for psychosis is justified not only by the fact that those who meet its criteria are at high risk of emergent psychosis, but also by the fact that they are already ill and in need of treatment. How best to intervene is not yet clear.

The prodromal phase before first episode psychosis (FEP) is described by patients and families as a period of rapid change in the content of thought accompanied by disturbed perception and impaired social engagement and functioning, Scott Woods (Yale University, New Haven, USA) told APAAM 2021.

Such changes can be captured by the Structured Interview for Psychosis-risk Syndromes (SIPS).1 When used after appropriate training, this is a reliable tool; and those it identifies – who are 2-3% of the general population – are eight times more likely than others to develop psychosis.2

The prodromal patient is both symptomatic and at risk, but progression is not inevitable2


A clinical dilemma

The existence of a high-risk state offers the prospect that intervention at this early stage may prevent progression to frank psychosis. But this will be the outcome in only 20-40% of cases.3,4

Not everyone is on the same trajectory: many people with apparently prodromal features remit spontaneously, while others have symptoms that persist but remain stable, and around 10% develop non-psychotic mood disorders.4

So the majority of people at clinical high risk (CHR) would not benefit from intervention, making this an ethically questionable approach.

That said, people at high risk of developing psychosis are already ill, in distress and experiencing impaired functioning,3 Professor Woods argued.


Does the CHR label bring stigma or opportunity?

Concern that describing someone as clinically high risk might be stigmatizing and cause harm is balanced by the possibility that empathic diagnosis relieves anxiety by providing an explanation for what is happening and also brings the opportunity of help.

Stigma from the high risk label is balanced by the chance it will bring help

What form this help might take remains uncertain, though. Recent meta-analysis of interventions including pharmacotherapy, cognitive behavioral therapy and family therapy found little evidence of efficacy overall and no evidence on which to choose between options.5,6 But the number of patients involved in these studies was small, and the need for further research is clear.

DSM-5 lists what it terms Attenuated Psychosis Syndrome as a “condition for further study” in which symptoms are less severe and more transient than in full psychosis, and with relatively maintained insight.

But DSM does not give the syndrome a diagnostic code, and this has hampered research and the development of potential therapies, Scott Woods argued.  

Our understanding of what it means to be CHR will hopefully be enhanced by ongoing study of people enrolled in the global Psychosis Risk Outcomes Network (ProNET) and the Trajectories and Predictors in the Clinical High Risk for Psychosis Population (PRESCIENT) consortium. These initiatives share clinical and biomarker protocols and will compare outcomes against matched healthy controls.


Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.


1. Woods SW et al. In Handbook of Attenuated Psychosis Syndrome Across Cultures, Li H et al. Springer, 2019

2. Powers et al. In Clinical Phenomenology, Tammaninga et al. Oxford, 2020

3. Woods SW et al. The “prodromal” patient: both symptomatic and at risk. CNS Spectrums 2001;6: 223-232

4. Woods SW et al. Lack of Diagnostic Pluripotentiality in Patients at Clinical High Risk for Psychosis: Specificity of Comorbidity Persistence and Search for Pluripotential Subgroups.  Schizophr Bull 2018; 44: 254-63

5. Devoe DJ et al. Negative Symptom Interventions in Youth at Risk of Psychosis: A Systematic Review and Network Meta-analysis. Schizophr Bull 2018; 44: 807-823

6. Davies C et al. Lack of evidence to favor specific preventive interventions in psychosis: a network meta-analysis. World Psychiatry 2018 ;17:196-209.

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