Clinical outcomes in individuals at clinical high risk of psychosis who do not transition to psychosis: a meta-analysis

Abstract

Aims The clinical outcomes of individuals at clinical high risk of psychosis (CHR-P) who do not transition to psychosis are heterogeneous and inconsistently reported. We aimed to comprehensively evaluate longitudinally a wide range of outcomes in CHR-P individuals not developing psychosis. Methods “Preferred Reporting Items for Systematic reviews and Meta-Analyses” and “Meta-analysis Of Observational Studies in Epidemiology”-compliant meta-analysis (PROSPERO: CRD42021229212) searching original CHR-P longitudinal studies in PubMed and Web of Science databases up to 01/11/2021. As primary analysis, we evaluated the following outcomes within CHR-P non-transitioning individuals: (a) change in the severity of attenuated psychotic symptoms (Hedge's g); (b) change in the severity of negative psychotic symptoms (Hedge's g); (c) change in the severity of depressive symptoms (Hedge's g); (d) change in the level of functioning (Hedge's g); (e) frequency of remission (at follow-up). As a secondary analysis, we compared these outcomes in those CHR-P individuals who did not transition vs. those who did transition to psychosis at follow-up. We conducted random-effects model meta-analyses, sensitivity analyses, heterogeneity analyses, meta-regressions and publication bias assessment. The risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale (NOS). Results Twenty-eight studies were included (2756 CHR-P individuals, mean age = 20.4, 45.5% females). The mean duration of follow-up of the included studies was of 30.7 months. Primary analysis: attenuated psychotic symptoms [Hedges’ g = 1.410, 95% confidence interval (CI) 1.002–1.818]; negative psychotic symptoms (Hedges’ g = 0.683, 95% CI 0.371–0.995); depressive symptoms (Hedges’ g = 0.844, 95% CI 0.371–1.317); and functioning (Hedges’ g = 0.776, 95% CI 0.463–1.089) improved in CHR-P non-transitioning individuals; 48.7% remitted at follow-up (95% CI 39.3–58.2%). Secondary analysis: attenuated psychotic symptoms (Hedges’ g = 0.706, 95% CI 0.091–1.322) and functioning (Hedges’ g = 0.623, 95% CI 0.375–0.871) improved in CHR-P individuals not-transitioning compared to those transitioning to psychosis, but there were no differences in negative or depressive symptoms or frequency of remission (p > 0.05). Older age was associated with higher improvements of attenuated psychotic symptoms (β = 0.225, p = 0.012); publication years were associated with a higher improvement of functioning (β = −0.124, p = 0.0026); a lower proportion of Brief Limited Intermittent Psychotic Symptoms was associated with higher frequencies of remission (β = −0.054, p = 0.0085). There was no metaregression impact for study continent, the psychometric instrument used, the quality of the study or proportion of females. The NOS scores were 4.4 ± 0.9, ranging from 3 to 6, revealing the moderate quality of the included studies. Conclusions Clinical outcomes improve in CHR-P individuals not transitioning to psychosis but only less than half remit over time. Sustained clinical attention should be provided in the longer term to monitor these outcomes.

Timing of antipsychotics and benzodiazepine initiation during a first episode of psychosis impacts clinical outcomes: Electronic health record cohort study

“…More on this, the duration of psychotic symptoms during a FEP may also be variable, with fleeting or spontaneous remission [about 19% of patients with a FEP (20)]. These cases are broadly classed as brief psychotic disorders (if druginduced psychosis can be ruled out), variably operationalized as Acute and Transient Psychotic Disorders [ATPD in the ICD (21)], Brief Psychotic Disorders [BPD in the DSM (16)] and Brief (Limited) Intermittent Psychotic Disorders (BLIPS/BIPS) in the Clinical High Risk state for Psychosis (CHR-P) research paradigm [68% of BLIPS meet criteria for ATPD (22); for recent reviews of this topic see (20, [23][24][25][26][27][28][29]]. In other FEP cases, the duration of presenting psychotic symptoms may be transient and closely related to the pathophysiological effect of illicit drugs of abuse on the brain and vanish once the substance has been cleared from the body.…”

A network analysis of anxiety, depressive, and psychotic symptoms and functioning in children and adolescents at clinical high risk for psychosis

“…Accordingly, preventive interventions are recommended as early as possible, with the goal of preventing, postponing, or ameliorating the onset of full-blown psychotic disorder (5,12). Individuals who meet the CHR-P criteria present a cumulative transition risk of 0.15 at 1 year, 0.19 at 2 years, 0.25 at 3 years, 0.27 at 4 years, and 0.28 at more than 4 years (5), and tend to maintain symptoms and poor functioning for years (14,15). Moreover, young people may never transition but present with chronic low functioning, fluctuating remission, recurrence and relapse of CHR-P status (6,(16)(17)(18).…”

“…Despite its utility for identifying individuals at imminent risk of psychosis, the CHR-P paradigm exhibits some limitations that merit further research. First, CHR-P individuals, at intake, show a large array of other full-fledged, clinically debilitating mental disorders, which can significantly hinder both treatment planning and the efficacy of interventions (14,(26)(27)(28)(29)(30)(31). Specifically, meta-analytical evidence indicates that 73% of CHR-P individuals present at least one comorbid mental disorder, with 41 and 15% suffering from depressive and anxiety disorders, respectively (28).…”

“…Also, the presenting complain CHR-P individuals seeks help for, may not be related to attenuated psychotic features and need to be considered actively ( 32 ). Depressive disorders, in turn, are related to negative symptoms and decreased remission from the CHR-P status, which may further impact general functioning ( 14 , 28 ). Second, both the CHR-P diagnostic criteria and current preventive interventions are mainly focused on positive symptoms, while frequently neglecting other psychopathological domains.…”

“…One of the exceptions is represented by the PACE clinic, which uses different modules to address symptomatology beyond attenuated psychotic features ( 18 , 33 ). The efficacy of early interventions is therefore limited to ameliorating positive symptoms and preventing psychosis ( 34 ), whereas there is a lack of evidence for their longitudinal improvement of depressive and negative symptoms and general functioning ( 14 , 35 ) (the step trial is an attempt to provide stepwise psychological and psychotropic interventions to address functioning overall as primary aim ( 36 ). Therefore, a crucial challenge is devising broader at-risk frameworks to capture early psychopathology manifestation and, at the same time, “maximize clinical utility” ( 37 ).…”