Progress in Neuro-Psychopharmacology and Biological Psychiatry
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
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
References (75)
A multidimensional (pharmacokinetic and clinical–biological) approach to neuroleptic response in schizophrenia. With particular reference to drug resistance
Schizophr. Res.
(1993)- et al.
Self-assessment of functional status in schizophrenia
J. Psychiatr. Res.
(2007) - et al.
Predicting schizophrenia patients' real-world behavior with specific neuropsychological and functional capacity measures
Biol. Psychiatry
(2008) - et al.
Factor structure of the MATRICS Consensus Cognitive Battery (MCCB) in schizophrenia
Schizophr. Res.
(2013) - et al.
Management of treatment resistance in schizophrenia
Biol. Psychiatry
(2001) - et al.
A path model investigation of neurocognition, theory of mind, social competence, negative symptoms and real-world functioning in schizophrenia
Schizophr. Res.
(2011) - et al.
Differential cognitive performances between schizophrenic responders and non-responders to antipsychotics: correlation with course of the illness, psychopathology, attitude to the treatment and antipsychotics doses
Psychiatry Res.
(2013) - et al.
Antipsychotic treatment resistance in schizophrenia associated with elevated glutamate levels but normal dopamine function
Biol. Psychiatry
(2014) - et al.
Functional milestones and clinician ratings of everyday functioning in people with schizophrenia: overlap between milestones and specificity of ratings
J. Psychiatr. Res.
(2012) - et al.
Determinants of work outcome in neuroleptic-resistant schizophrenia and schizoaffective disorder: cognitive impairment and clozapine treatment
Psychiatry Res.
(2010)
A prospective comparative study of risperidone long-acting injectable for treatment-resistant schizophrenia with dopamine supersensitivity psychosis
Schizophr. Res.
Neurochemical sensitization in the pathophysiology of schizophrenia: deficits and dysfunction in neuronal regulation and plasticity
Neuropsychopharmacology
Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study
Lancet
High-dose quetiapine in treatment refractory schizophrenia
Schizophr. Res.
Negative symptoms and everyday functioning in schizophrenia: a cross-sectional study in a real world-setting
Psychiatry Res.
Assessing everyday functioning in schizophrenia: not all informants seem equally informative
Schizophr. Res.
The natural history and pathophysiology of treatment resistant schizophrenia
J. Psychiatr. Res.
Discriminant cognitive factors in responder and non-responder patients with schizophrenia
Eur. Psychiatry
Determinants of different aspects of everyday outcome in schizophrenia: the roles of negative symptoms, cognition, and functional capacity
Schizophr. Res.
Dopamine supersensitivity psychosis as a pivotal factor in treatment-resistant schizophrenia
Psychiatry Res.
Neuropsychological substrates and everyday functioning implications of prospective memory impairment in schizophrenia
Schizophr. Res.
Remission in schizophrenia: proposed criteria and rationale for consensus
Am. J. Psychiatry
The brief assessment of cognition in schizophrenia. Normative data for the Italian population
Neurol. Sci.
Impact of atypical antipsychotics on quality of life in patients with schizophrenia
CNS Drugs
The practical management of refractory schizophrenia — the Maudsley Treatment REview and Assessment Team service approach
Acta Psychiatr. Scand.
Combined cognitive remediation and functional skills training for schizophrenia: effects on cognition, functional competence, and real-world behavior
Am. J. Psychiatry
Multiple versus single antipsychotic agents for hospitalized psychiatric patients: case–control study of risks versus benefits
Am. J. Psychiatry
Effect of psychosocial interventions on social functioning in depression and schizophrenia: meta-analysis
Br. J. Psychiatry
Dopamine synthesis capacity in patients with treatment-resistant schizophrenia
Am. J. Psychiatry
Social/communication skills, cognition, and vocational functioning in schizophrenia
Schizophr. Bull.
The 2009 schizophrenia PORT psychosocial treatment recommendations and summary statements
Schizophr. Bull.
A naturalistic controlled study of relapsing schizophrenic patients with tardive dyskinesia and supersensitivity psychosis
J. Psychopharmacol.
A multiple-center, randomized, double-blind, placebo-controlled study of oral aripiprazole for treatment of adolescents with schizophrenia
Am. J. Psychiatry
Identification of increased genetic risk scores for schizophrenia in treatment-resistant patients
Mol. Psychiatry
The influence of illness-related variables, personal resources and context-related factors on real-life functioning of people with schizophrenia
World Psychiatry
Cluster analysis of cognitive deficits may mark heterogeneity in schizophrenia in terms of outcome and response to treatment
Eur. Arch. Psychiatry Clin. Neurosci.
Direct measurement of disability
Psychiatry (Edgmont)
Cited by (113)
Changes in immunoglobulin levels during clozapine treatment in schizophrenia
2024, Brain, Behavior, and ImmunityVerbal and visual learning ability in patients with treatment-resistant schizophrenia: A 1-year follow-up study
2023, Schizophrenia Research: CognitionA pilot-study to examine motor cortical plasticity as a neuro-marker of antipsychotic treatment response in schizophrenia
2023, Asian Journal of PsychiatryDecrease in gamma-band auditory steady-state response in patients with treatment-resistant schizophrenia
2023, Schizophrenia Research