Antipsychotic prescription, assumption and conversion to psychosis: resolving missing clinical links to optimize prevention through precision

Abstract

The current concept of clinical high-risk(CHR) of psychosis relies heavily on “below-threshold” (i.e. attenuated or limited and intermittent) psychotic positive phenomena as predictors of the risk for future progression to “above-threshold” positive symptoms (aka “transition” or “conversion”). Positive symptoms, even at attenuated levels are often treated with antipsychotics (AP) to achieve clinical stabilization and mitigate the psychopathological severity. The goal of this study is to contextually examine clinicians’ decision to prescribe AP, CHR individuals’ decision to take AP and psychosis conversion risk in relation to prodromal symptoms profiles. CHR individuals (n = 600) were recruited and followed up for 2 years between 2016 and 2021. CHR individuals were referred to the participating the naturalistic follow-up study, which research procedure was independent of the routine clinical treatment. Clinical factors from the Structured Interview for Prodromal Syndromes (SIPS) and global assessment of function (GAF) were profiled via exploratory factor analysis (EFA), then the extracted factor structure was used to investigate the relationship of prodromal psychopathology with clinicians’ decisions to AP-prescription, CHR individuals’ decisions to AP-taking and conversion to psychosis. A total of 427(71.2%) CHR individuals were prescribed AP at baseline, 532(88.7%) completed the 2-year follow-up, 377(377/532, 70.9%) were taken AP at least for 2 weeks during the follow-up. EFA identified six factors (Factor-1-Negative symptoms, Factor-2-Global functions, Factor-3-Disorganized communication & behavior, Factor-4-General symptoms, Factor-5-Odd thoughts, and Factor-6-Distorted cognition & perception). Positive symptoms (Factor-5 and 6) and global functions (Factor-2) factors were significant predictors for clinicians’ decisions to AP-prescription and CHR individuals’ decisions to assume AP, whereas negative symptoms (Factor-1) and global functions (Factor-2) factors predicted conversion. While decisions to AP-prescription, decisions to AP-taking were associated to the same factors (positive symptoms and global functions), only one of those was predictive of conversion, i.e. global functions. The other predictor of conversion, i.e. negative symptoms, did not seem to be contemplated both on the clinician and patients’ sides. Overall, the findings indicated that a realignment in the understanding of AP usage is warranted.

Baseline antipsychotic prescription and short‐term outcome indicators in individuals at clinical high‐risk for psychosis: Findings from the Parma At‐Risk Mental States (PARMS) program

“…In particular, this risk was not related to differences in pre‐test risk enrichment across the studies (Raballo et al, 2021b). In 2022, other investigations on single, longitudinal CHR‐P cohorts confirmed the negative prognostic value associated with baseline AP exposure (Preti et al, 2022; Zeng et al, 2022), which is probably due to different factors that are still unknown and under‐investigated (Zhang et al, 2022). In particular, baseline AP exposure in CHR‐P individuals may be considered as a functional equivalent of the psychometric transition to psychosis (Preti et al, 2022), as already postulated in the original ‘Ultra High‐Risk’ model (Yung et al, 2003).…”

Baseline benzodiazepine exposure is associated with greater risk of transition in clinical high-risk for psychosis (CHR-P): a meta-analysis

“…It should be noted that in CHR-P individuals, baseline exposure to antipsychotics is associated with a greater risk of transition to psychosis both at a meta-analytical level (Raballo et al, 2020b; Raballo, Poletti, & Preti, 2023) and in subsequent field testing and reanalysis of available cohorts (Preti et al, 2022; Zhang et al, 2022), and it might be that BDZ – although this info is omitted in the source literature - could have been co-administered with antipsychotics, thereby capturing part of the AP-related pro-transition effect.…”

“…We also lacked details about the profile of symptoms at baseline by drug prescription, thus we were unable to determine whether BDZs were effectively prescribed to CHR-P help-seekers with more severe symptoms, e.g., with higher levels of anxiety or depression symptoms. There is some evidence that prescription of antipsychotics to help-seeking CHR-P is related to the severity of positive symptoms and greater impairment of global functioning (Zhang et al, 2022). Although we can surmise that the prescription of BDZ, especially when concomitant to the prescription of antipsychotics or antidepressants, might be related to greater severity at presentation, the lack of available information impedes a direct meta-analytical testing.…”

“…Forest plot of the risk ratio of conversion to psychosis between CHR who were or were not exposed to benzodiazepines at baseline. (Zhang et al, 2022). Although we can surmise that the prescription of BDZ, especially when concomitant to the prescription of antipsychotics or antidepressants, might be related to greater severity at presentation, the lack of available information impedes a direct meta-analytical testing.…”

Comprehensive review of multidimensional biomarkers in the ShangHai At Risk for Psychosis (SHARP) program for early psychosis identification

“…The occurrence and development of psychosis is not only a change in behavioral appearance or brain function but also a characteristic change in the characteristics of immunoinflammatory markers in the early stage. The SHARP team 29,34,35 found that the imbalance of The results suggest that antipsychotic drugs should not be used prematurely in the at-risk population 27,28,40 as they are only valuable for <15% of the CHR population of a certain subtype [41][42][43] ; it is necessary to carry out individualized new intervention technologies for CHR subtypes of different biological dimensions. 3 Approximately 30% of the CHR population may recover naturally without intervention, and a large proportion of CHR are teenagers.…”