Speed of Psychosis Progression in People at Ultra-High Clinical Risk: A Complementary Meta-analysis

The transition to psychosis in patients at ultra-high clinical risk (UHR; as defined elsewhere¹) is most likely to occur within the first 2 years after presentation to clinical services (risk estimate, 29%; 95% CI, 23-36).² After this phase, the speed of psychosis progression tends to plateau from the third year,² reaching approximately 35% after 10 years.³ However, the exact speed of psychosis progression at a particular point during the critical first 2 years is unclear, preventing clinical advancements in the field.

We used the pooled cumulative transition curve from our previous meta-analysis; survival curves from 6 independent studies (n = 1327) covering 24 months were digitally measured and statistically combined.² The gradient of the cumulative curve was calculated to determine the speed of psychosis progression in UHR individuals. The chance of transition over a given month after presentation (Figure 1) and the cumulative chance of transition given transition occurs by 2 years (Figure 2) were modeled using an exponential regression model; we selected this model because it ensured the probability of transition remained finite at zero months and greater than zero at all future points.

The gradient of the smoothed combined cumulative transition is shown in Figure 1. It indexes the speed of psychosis progression in a UHR sample, showing the probability of transition to psychosis in any given month after presentation. Figure 2 shows the cumulative probability of transition within the subgroup of UHR patients who will transition to psychosis in the first 2 years.

The speed of psychosis progression in UHR people is greatest during the first months after presentation. Half of UHR people who progress to psychosis within 2 years will do so within the first 8 months since presentation to high-risk services.

These findings are important, particularly because the duration of the UHR state is known to impact clinical outcomes⁴ and underlying neurobiology.⁵ First, they can be used to directly inform clinicians of the risk for psychosis in a UHR patient (eg, the risk for transition between monthly meetings with a psychologist at 12 months since first presentation can be determined from Figure 1 as approximately 1%). Second, given that cognitive behavioral therapy is the recommended and most effective focused intervention for UHR individuals,⁶ such treatment should be offered on a weekly basis, at least during the first 8 months since presentation to the high-risk service. It seems relevant to reduce the waiting list time to start the treatment and to offer close-in weekly monitoring to UHR patients who refuse the psychological intervention. There are also some diagnostic implications for the responsible clinicians. Our finding that the speed of psychosis transition is highest in the first month (2%) raises the possibility that some patients may have already been psychotic but underreporting at the time of the initial assessment.⁷ High-risk services should place more emphasis in conducting a prolonged and ongoing careful assessment to rule out concealed psychotic symptoms. Diagnostic skepticism should be considered when treating UHR patients included on the basis of brief limited intermittent psychotic symptoms, which is already clinically closer to the psychosis threshold. A 2-step approach—excluding patients who had reported meeting the UHR criteria at first baseline assessment but disclosed overthreshold psychotic experiences consistent with transition at a second assessment conducted in the first month— could be adopted.⁷ Finally, the current results may inform the planning and development of research studies in UHR individuals (eg, power calculations). For example, future neuroimaging studies may want to plan sequential scans in the first months to better clarify the dynamic neurobiological processes underlying the onset of psychosis in UHR individuals.

Corresponding Author: Paolo Fusar-Poli, MD, PhD, RCPsych, Department of Psychosis Studies, Institute of Psychiatry, PO63, De Crespigny Park, London SE58AF, England (p.fusar@libero.it).

Published Online: April 22, 2015. doi:10.1001/jamapsychiatry.2015.0094.

Author Contributions: Drs Kempton and Fusar-Poli had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Kempton, Fusar-Poli.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Kempton, Fusar-Poli.

Critical revision of the manuscript for important intellectual content: Bonoldi, Valmaggia, McGuire, Fusar-Poli.

Statistical analysis: Kempton, Fusar-Poli.

Obtained funding: McGuire, Fusar-Poli.

Administrative, technical, or material support: Bonoldi, McGuire, Fusar-Poli.

Study supervision: McGuire, Fusar-Poli.

Conflict of Interest Disclosures: None reported.

Funding/Support: Dr Kempton was funded by a Medical Research Council Fellowship (grant MR/J008915/1). Dr Fusar-Poli is funded by the Department of Psychosis Studies (King’s College London, London, England) and by the South London and the Maudsley NHS Foundation Trust.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.