Intervention strategies for ultra-high risk for psychosis: Progress in delaying the onset and reducing the impact of first-episode psychosis

Abstract

Over a quarter of a century ago, the formulation of the "at risk mental state" and operational criteria to prospectively identify individuals at "clinical" or "ultra-high risk" (UHR) for psychosis created a global wave of research momentum aimed at predicting and preventing first-episode psychosis. A substantial number of randomized controlled trials (RCTs) were conducted to determine if transition to psychosis could be delayed or even prevented. The efficacy of a range of interventions was examined, with standard meta-analyses clearly indicating that these could at least delay transition for 1-2 years and that outcomes improve. Recently, network meta-analyses have attempted to identify the most effective intervention. These highlighted the fact that no one form of intervention is superior to the rest, a finding interpreted in such a way as to create doubts concerning the value of intervening. These doubts have been reinforced by a subsequent Cochrane review which judged the quality of the evidence as low or very low. Here, we report a narrative review of findings from RCTs and meta-analyses on the efficacy of interventions in UHR. We also critique the network meta-analyses and the Cochrane review, and indicate that many of the trials were of the highest possible quality for such research, and were published in top ranked psychiatry journals, which demand such quality. Although outcomes vary, and the UHR group is clearly heterogeneous, we highlight the clinical benefits of psychosocial treatment. The next generation of clinical trials seek to elucidate the optimal type, duration and sequence of interventions.

Keywords: At risk mental state; Clinical high risk; Meta-analyses; Psychosis; Randomized controlled trials; Ultra-high risk.