Treatment resistant schizophrenia is associated with the worst community functioning among severely-ill highly-disabling psychiatric conditions and is the most relevant predictor of poorer achievements in functional milestones

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Highlights

  • Treatment resistant schizophrenia (TRS) patients differed from responders in many clinical respects.

  • Treatment resistant schizophrenia (TRS) patients had less achievements in functional milestones than responders.

  • Diagnosis of treatment resistant schizophrenia (TRS) was a consistent predictor of worse psychosocial functioning.

Abstract

The aim of this work was to compare achievements in milestones of community functioning in highly disabling psychiatric conditions, including treatment resistant schizophrenia (TRS), schizophrenia (responsive to antipsychotics), bipolar disorder, and anxiety/depressive diseases. Also, we investigated the predictors of community functioning outcomes across several domains.

Among consecutive patients screened, 188 met inclusion criteria and 118 ultimately entered the study. Diagnosis of TRS was made by stringent criteria, including historic and perspective evaluations and excluding potential confounding factors. Achievements in functional milestones of everyday living were recorded. Performances in discrete cognitive tasks were assessed. The Positive and Negative Syndrome Scale, the Personal and Social Performance Scale, the Drug Attitude Inventory-10, and the Quality of Life Enjoyment and Satisfaction Questionnaire were administered.

TRS patients showed the highest impairment in community functioning among diagnostic groups. TRS was found to have more severe psychopathology, more impaired cognitive functioning, and poorer psychosocial adjustment compared to all the other groups. In the whole sample, the main predictors of community functioning were the diagnostic group (with TRS diagnosis associated with worst functioning) and achievements in the other functional milestones. In psychotic patients, however, the main predictors of community functioning were clinical and psychopathological variables.

These results may support the hypothesis that TRS represents a separate schizophrenia subtype, with its own neurobiology, psychopathology and clinical course. Our results identify a group of modifiable predictors to be addressed to prevent community disability.

Introduction

Treatment resistant schizophrenia (TRS) is a severe clinical condition with poor or no responsiveness to antipsychotic treatment affecting at least one third of schizophrenia patients (Lindenmayer, 2000), who do not respond or respond poorly to antipsychotic medications (Kane, 1996). The lack of response to antipsychotics is associated in these patients with persisting psychotic symptoms (both positive and negative) and cognitive dysfunctions (de Bartolomeis et al., 2013, Gilbert et al., 2014, Iasevoli et al., 2013), all of which have been regarded to predispose to social dysfunctions in schizophrenia patients (Burton et al., 2013, Galderisi et al., 2014), contributing to long-term disability and poor community functioning (Dickinson et al., 2007, Rocca et al., 2014, Rosenheck et al., 2006, Twamley et al., 2002, Twamley et al., 2008).

Despite an extensive literature on inadequate social adaptations in schizophrenia patients is available (Couture et al., 2011, Harvey, 2009, Harvey et al., 2009, Strassnig et al., 2015), very few data have been to date provided on the extent of social dysfunctions and community functioning in TRS, compared to responder schizophrenia patients and to other highly disabling psychiatric conditions. High rates of unemployment in a mixed sample of TRS and schizoaffective patients were found and were related to impaired neurocognitive performances (Kaneda et al., 2010), however no comparison was given with other psychiatric conditions or with antipsychotic responder schizophrenia patients. As TRS has been regarded as a more severe subtype of schizophrenia, with putative distinct neurobiological underpinnings (Demjaha et al., 2012, Demjaha et al., 2014, Frank et al., 2015, Quarantelli et al., 2014, Szeszko et al., 2012) and poorer prognosis (Kolakowska et al., 1985, Sheitman and Lieberman, 1998), it is expected that TRS patients will suffer from more serious disability.

Quantitative evaluation of disability and social competence in schizophrenia patients has been a challenging issue. Indeed, self-reported questionnaires, such as assessment of quality of life or of skills profile, are often jeopardized by patients' lack of complete insight on their pathological conditions (Bowie et al., 2007, Sabbag et al., 2011), while increasing reliability may be granted to informants' reports, high-contact clinicians' reports, and assessments of real-word everyday functioning (Harvey and Velligan, 2011). Measurement of everyday functioning has been accomplished by two approaches: ratings of real-world functioning using structured or performance-based assessments (Harvey et al., 2007, Harvey et al., 2011, Leifker et al., 2011), and the examination of functional achievements (e.g., marriage; independent living; competitive employment), the so-called functional milestones (Harvey et al., 2012). Therefore, milestones of real-world functioning are a reliable direct measure of everyday community functioning and may evaluate disability in multiple everyday functional domains, whose impairment is common in schizophrenia patients (Murray and Lopez, 1997), including vocational, residential, and social domains (Bowie et al., 2008, Twamley et al., 2002), and whose attainment is considered basic to social living (Wiersma et al., 2000).

The main aim of this work was to evaluate whether significant differences in functional milestones' achievements can be detected among TRS, schizophrenia responders and patients with non-schizophrenic highly disabling psychiatric conditions. Additional aims were: i) to evaluate whether significant differences can be found among TRS, schizophrenia responders and the other patients of the sample in multiple demographic, clinical, therapy-related, psychopathological, cognitive and psychosocial variables; ii) to dissect, among the above-mentioned groups of variables, the predictors of outcomes in community functioning, as measured by functional milestones, in the whole sample of patients; and iii) to identify the predictors of achievement in functional milestones in the sample of psychotic patients.

Section snippets

Study design

This cross-sectional, naturalistic trial was conducted at the Outpatient Unit on Treatment Resistant Psychosis, Section of Psychiatry, Department of Neuroscience, University “Federico II” of Naples, from September 2013 to December 2014. All consecutive patients meeting criteria for eligibility were recruited. All patients signed a written informed consent form, approved by the participating institution. Patients were adequately informed of all aspects regarding the participation and the purpose

Demographics and clinical data

188 consecutive patients were considered eligible for the study and 118 of them were included in the study. A flow diagram of the study is provided in Fig. 1. Among patients not included in the study, 45 met exclusion criteria, 7 failed to give informed consent, 8 were possible TRS whose clinical history cannot be reliably documented, and 10 were pseudo-pharmacoresistant schizophrenia patients whose putative factors of pseudo-pharmacoresistance cannot be removed. Namely, 75 schizophrenia

Discussion

This study was conducted to investigate the extent of disability in community functioning in four groups of severely-ill psychiatric patients, and to establish the determinants of disability in these ones.

Specifically, the first aim of this study was to evaluate whether a condition of treatment resistant schizophrenia, assessed by rigorous and structured definitions, could determine poorer levels of community functioning compared to other highly disabling psychiatric conditions, even including

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