Early detection and intervention evaluation for people at risk of psychosis: multisite randomised controlled trial

Abstract

Objective To determine whether cognitive therapy is effective in preventing the worsening of emerging psychotic symptoms experienced by help seeking young people deemed to be at risk for serious conditions such as schizophrenia.Design Multisite single blind randomised controlled trial.Setting Diverse services at five UK sites.Participants 288 participants aged 14-35 years (mean 20.74, SD 4.34 years) at high risk of psychosis: 144 were assigned to cognitive therapy plus monitoring of mental state and 144 to monitoring of mental state only. Participants were followed-up for a minimum of 12 months and a maximum of 24 months.Intervention Cognitive therapy (up to 26 (mean 9.1) sessions over six months) plus monitoring of mental state compared with monitoring of mental state only. Main outcome measures Primary outcome was scores on the comprehensive assessment of at risk mental states (CAARMS), which provides a dichotomous transition to psychosis score and ordinal scores for severity of psychotic symptoms and distress. Secondary outcomes included emotional dysfunction and quality of life.Results Transition to psychosis based on intention to treat was analysed using discrete time survival models. Overall, the prevalence of transition was lower than expected (23/288; 8%), with no significant difference between the two groups (proportional odds ratio 0.73, 95% confidence interval 0.32 to 1.68). Changes in severity of symptoms and distress, as well as secondary outcomes, were analysed using random effects regression (analysis of covariance) adjusted for site and baseline symptoms. Distress from psychotic symptoms did not differ (estimated difference at 12 months −3.00, 95% confidence interval −6.95 to 0.94) but their severity was significantly reduced in the group assigned to cognitive therapy (estimated between group effect size at 12 months −3.67, −6.71 to −0.64, P=0.018).Conclusions Cognitive therapy plus monitoring did not significantly reduce transition to psychosis or symptom related distress but reduced the severity of psychotic symptoms in young people at high risk. Most participants in both groups improved over time. The results have important implications for the at risk mental state concept.Trial registration Current Controlled Trials ISRCTN56283883.

The slow death of the concept of schizophrenia and the painful birth of the psychosis spectrum

“…Emerging evidence from at-risk samples was a wake-up call to early intervention (Fusar-Poli et al 2014;McGorry & Nelson, 2016): (i) The framework of 'transition' as an end result fails to explain the heterogeneity in clinical and functional outcome, (ii) Studies that control for 'false transition' representing natural fluctuation of an existing psychotic state find very low 'transition' rates (Morrison et al 2012), (iii) An over-reliance on positive psychotic symptoms sets a self-limiting barrier to capture early expression of nonspecific psychopathology, the severity of which is 'marked' but not 'caused' by attenuated psychosis, (iv) 'Clinical High Risk' criteria majorly identify individuals with diagnosed states of anxiety/depression and/ or drug use who also display subtle psychotic experiences, which research has shown is a marker forbut not necessarily the cause of -relatively poor outcome (Perlis et al 2011;Wigman et al 2014;McAusland et al 2015). Thus, early treatment of psychopathology (including treatment of subtle psychotic experiences), in states of anxiety/depression/drug use with a degree of psychosis admixture will naturally improve outcome; it does not seem necessary or valid, however, to claim that this effort represents 'prevention of schizophrenia' ( .…”

Comparing time use in individuals at different stages of psychosis and a non-clinical comparison group

“…Data for the ARMS sample (N = 199) were taken from baseline assessments in the Early Detection and Intervention Evaluation (EDIE-II) study (Morrison et al, 2012), a multi-centre randomised controlled trial of CBT for helpseeking individuals with at-risk mental states, defined using the Comprehensive Assessment of At-Risk Mental States (CAARMS; Yung et al, 2002). None of the sample met DSM-IV criteria for psychotic disorders, but 67% had at least one other DSM-IV diagnosis at study entry.…”

Research Strategies and Priorities to Improve the Lives of People With Schizophrenia: Executive Summary of the Ernst Struungmann Forum on Schizophrenia

“…Better understanding is needed because current evidence suggests that while we may be able to delay the onset of schizophrenia for 1-2 years in people in an at-risk mental state, we may not be able to prevent its eventual onset. 14,15 One conclusion from these findings is that it is too late to intervene at the point when a person starts to exhibit prodromal indicators of schizophrenia (ie, the current best-practice approach). Therefore, an alternative, albeit untested, approach is to intervene much earlier (eg, 9-13 years of age) when academic and behavioral difficulties typically emerge.…”