Validation and refinement of the clinical staging model in a French cohort of outpatient with schizophrenia (FACE-SZ)

Highlights

• Clinical staging for schizophrenia can be improved by adding assessment of mood symptoms and cognitive handicap

• Early treatment of depression and cognitive remediation might reduce the number of patients in the most severe stages

• This data suggests a reverse gear to clinical staging, traditionally thought as uniformly progressive.

Abstract

Objective

Existing staging models have not been fully validated. Thus, after classifying patients with schizophrenia according to the staging model proposed by McGorry et al. (2010), we explored the validity of this staging model and its stability after one-year of follow-up.

Method

Using unsupervised machine-learning algorithm, we classified 770 outpatients into 5 clinical stages, the highest being the most severe. Analyses of (co)variance were performed to compare each stage in regard to socio-demographics factors, clinical characteristics, co-morbidities, ongoing treatment and neuropsychological profiles.

Results

The precision of clinical staging can be improved by sub-dividing intermediate stages (II and III). Clinical validators of class IV include the presence of concomitant major depressive episode (42.6% in stage IV versus 3.4% in stage IIa), more severe cognitive profile, lower adherence to medication and prescription of >3 psychotropic medications. Follow-up at one-year showed good stability of each stage.

Conclusion

Clinical staging in schizophrenia could be improved by adding clinical elements such as mood symptoms and cognition to severity, relapses and global functioning. In terms of therapeutic strategies, attention needs to be paid on the factors associated with the more stages of schizophrenia such as treatment of comorbid depression, reduction of the number of concomitant psychotropic medications, improvement of treatment adherence, and prescription of cognitive remediation.

Introduction

Clinical staging has been widely used to predict course and to optimize treatment in most chronic medical disorders, but until recently it has relatively been neglected in psychiatry (Fava and Kellner, 1993). Clinical staging differs from conventional diagnostic practice in that it defines not only the extent of progression of a disorder at a given point in time, but also where a person currently lies along the illness course continuum (McGorry et al., 2010). The last two decades have seen the gradual emergence of clinical staging in psychiatric disorders. In schizophrenia, staging models are likely to have heuristic utility in the understanding of illness progression, improving the exploration of relationships of stages with biomarkers and psychosocial risk factors. A major advantage of clinical staging models is the guidance they provide to clinicians to estimate prognosis and to define therapeutic strategies relevant for each stage.

Different theoretical staging models, have been proposed such as stage 1 as the “latent stage” to stage IV as the “chronic and refractory stage” (McGorry et al., 2010; Scott et al., 2013) without necessarily identifying external validators of these different propositions. Few follow-up studies have as of yet been performed and most of them have been done in the field of bipolar disorder (Rosa et al., 2014; Magalhães et al., 2012; Grande et al., 2014). In schizophrenia, to the best of our knowledge, only three studies have applied clinical staging models in individuals with schizophrenia. In a sample of 171 individuals at a high risk of psychosis followed-up over 3 years, Carrion and colleagues showed that the severity of early prodromal symptoms plays a critical role in determining clinical outcome, including the risk of psychosis, time to emergence and medication treatment (Carrión et al., 2017). However, this study only focused on the early phases of the illness and transition to psychosis. In a sample of 203 patients with schizophrenia, Ortiz et al. investigated whether clinical and psychopathological differences exist between first-episode schizophrenia and multiple-episode patients; however they focused on hospitalized patients (Ortiz et al., 2017). Tedja et al., concluded that clinical staging was applicable to schizophrenia (Tedja A, 2017) by investigating a retrospective cohort of 649 patients diagnosed with schizophrenia, followed up for 3 years. However, in order to fulfill the defined staging criteria, only 20% of the initial sample could be assignable to a clinical stage, thereby limiting the generalization of their results. To date, no study has applied a clinical staging framework, as defined by McGorry et al. (2010) (Scott et al., 2013), in a large systematically recruited cohort of outpatients with schizophrenia.

The present study has three aims: (i) to classify patients with schizophrenia according to the staging model proposed by McGorry et al. (2010), using number of episodes, daily functioning and current illness severity, in a prospective cohort of 770 patients (ii) to use clinical, cognitive and treatment characteristics to explore the validity of this staging model, and (iii) to explore the stability of these different stages after one-year of follow-up.