Understanding the impact of persistent symptoms in schizophrenia: Cross-sectional findings from the Pattern study

https://doi.org/10.1016/j.schres.2015.09.001Get rights and content

Abstract

Background

The high societal burden of schizophrenia is largely caused by the persistence of symptoms and accompanying functional impairment. To date, no studies have specifically assessed the course of persistent symptoms or the individual contributions of positive and negative symptoms to patient functioning. The cross-sectional analysis of the Pattern study provides an international perspective of the burden of schizophrenia.

Methods

Clinically stable outpatients from 140 study centers across eight countries (Argentina, Brazil, Canada, France, Germany, Italy, Spain and the United Kingdom) were assessed using clinical rating scales: Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Schizophrenia (CGI-SCH) Scale and the Personal and Social Performance (PSP) Scale. Additional measures included patient-reported outcomes, patient socio-demographic variables, living situation, employment and resource use.

Results

Overall, 1379 patients were assessed and analyzed and had similar sociodemographic characteristics across countries, with 61.6% having persistent positive and/or negative symptoms. Positive and negative symptoms had been persistent for a mean of 9.6 and 8.9 years (SD: 8.8 and 9.6), respectively. Approximately 86% of patients had a functional disability classified as greater than mild. Patients with a higher PANSS Negative Symptom Factor Score were more likely to have a poorer level of functioning.

Conclusions

This analysis examines individual contributions of persistent positive and negative symptoms on patient functioning in different countries. A high prevalence of patients with persistent symptoms and functional impairment was a consistent finding across countries. Longitudinal observations are necessary to assess how to improve persistent symptoms of schizophrenia and overall patient functioning.

Introduction

Schizophrenia is a severe mental disorder associated with high personal, family and societal burden (Van Os and Kapur, 2009). It is characterized by the presence of a variety of symptoms, which are commonly divided into three main symptom domains: 1) psychotic symptoms such as delusions, hallucinations (reality distortion) and disorganization (thought disorders and bizarre behavior); 2) negative symptoms, which include affective flattening, paucity of thought or speech, lack of motivation and emotional and social withdrawal; and 3) cognitive impairment (especially in memory, attention and executive function) (Liddle, 1987, Malla et al., 1993). The annual incidence of schizophrenia averages 15 per 100,000 and the lifetime prevalence is approximately 1% (Tandon et al., 2008). Schizophrenia is one of the most costly mental disorders in terms of human suffering and societal expenditure. This high burden to patients, their families and wider society is predominantly caused by the persistence of symptoms and occurrence of relapse throughout the course of illness.

A substantial proportion of patients with schizophrenia experience residual and unremitting positive symptoms despite antipsychotic treatment (Suzuki et al., 2012, Suzuki et al., 2011). Approximately 70% of patients treated with antipsychotics show improvement in positive symptoms in the short-term (up to 6 months). However, the response is not consistent or fully effective for all patients (Menezes et al., 2006, Novick et al., 2007, Novick et al., 2009, Van Os and Kapur, 2009). Indeed, it has been estimated that around two-thirds of patients continue to experience significant symptoms two years after treatment initiation, and approximately one-third will continue to experience these symptoms six years after diagnosis (Hegarty et al., 1994, Menezes et al., 2006, Novick et al., 2007, Novick et al., 2009). Insufficiently controlled positive symptoms can lead to poor patient outcomes, including relapse, rehospitalization, impaired functioning and a reduced quality of life (Norman et al., 1999, Norman et al., 2001, Novick et al., 2009, Csernansky and Schuchart, 2002, Doering et al., 1998, Postrado and Lehman, 1995, Menezes et al., 2006, Novick et al., 2007, Novick et al., 2009, Jordan et al., 2014).

A recent follow-up study of individuals experiencing a first psychotic episode has challenged this negative prognosis. The AESOP-10 study followed up a cohort of 557 people with a first psychotic episode. Of the 126 patients with schizophrenia who were reevaluated about half of them were classified as having a good end state (Morgan et al., 2014). Seventy percent of the cases who were followed up had experienced at least a period of sustained remission. However, these results are somehow in conflict with recent review that found that the proportion of those with schizophrenia who recover on both symptom and functional outcome is modest (approximately 14%). The discrepancies can be explained by disparities in the patient samples, whether first-episode or not, but also by the lack of consistent definitions of remission and recovery. Recovery should be conceptualized as a multifaceted process, in which symptoms, functioning and patient perception need to be taken into account (McGrath et al., 2014). Recovery obviously depends on remission. Nevertheless, there are a number of other intervening factors affecting recovery that are responsible for the marked variation in outcome observed (Menendez-Miranda et al., 2015, Jordan et al., 2014).

At any point in time, including during the first episode of illness, negative symptoms affect up to 60% of patients with schizophrenia (Bobes et al., 2010), with 30% having primary negative symptoms (Buchanan, 2007, Stahl and Buckley, 2007). Currently available antipsychotics may not have a direct effect on primary negative symptoms (Erhart et al., 2006); therefore, many patients experience persistent negative symptoms even after control of their positive symptoms (Stahl and Grady, 2004, Chue and Lalonde, 2014). The severity of negative symptoms is a predictor of poor patient functioning, also contributing, to a greater extent than positive symptoms, to worse patient outcomes (Fervaha et al. (2014a,b). Negative symptoms affect the ability of the patient to live independently, perform activities of daily living, engage in social activity, maintain personal relationships and participate in work or study (Rabinowitz et al., 2012, White et al., 2009, Novick et al., 2009). This impact is often evident even within one to two years following treatment of a first episode of illness (Cassidy et al., 2010, Jordan et al., 2014).

Resolution of persistent symptoms is necessary to achieve complete remission and serves to expand patient progress beyond just “stability” and towards improved social and occupational functioning. Furthermore, psychosocial therapies and rehabilitation are most effective when both positive and negative symptoms are effectively controlled (Andreasen et al., 2005). Many patients experience persistent morbidity over the course of their illness and the attainment of remission (defined as a ‘mild or less’ symptom level for the eight core Positive and Negative Syndrome Scale [PANSS] symptoms for at least six consecutive months) remains a significant challenge (Andreasen et al., 2005). A recent literature review of remission in schizophrenia reported that only 45–70% of first-episode and multi-episode patients fulfilled remission criteria at some point during treatment (Lambert et al., 2010).

A number of epidemiological cohort studies have been followed but none has specifically evaluated the natural course of persistent positive and negative symptoms of schizophrenia or compared them between countries (Buchanan, 2007, Chakos et al., 2006; Haro et al., 2003a; Haro et al., 2003b). The Pattern study was designed to evaluate the burden and course of schizophrenia, patient-reported outcomes, healthcare resource utilization and associated costs for patients with persistent symptoms of schizophrenia, not conditioned by any particular therapy or intervention, under standard routine clinical practice. In addition, family members and other informal carers were assessed for their burden and associated costs with caring for these patients. This study is unique in the field of schizophrenia owing to its analysis of the individual contributions of positive and negative persistent symptoms on patient functioning across countries. Whereas previous studies have evaluated the course of illness in patients with schizophrenia by assessing overall symptom burden, the Pattern study examines individual symptom subgroups. The study consists of two phases: a cross-sectional assessment, which forms the baseline observation; and a longitudinal assessment, in order to collect data on all patients who were not in recovery at baseline. The aim of this study is to describe the characteristics of the patients with schizophrenia receiving outpatient treatment in different countries and to examine the relationship between the persistence of different types of symptoms and patient functioning.

Section snippets

Study design

Pattern is an international, multicenter, non-interventional, prospective, cohort study of schizophrenia patients attending psychiatric outpatient clinics. The study was conducted by psychiatrists treating patients with schizophrenia in outpatient facilities. Recruitment within the sites was based on a sequential selection from patients with a diagnosis of schizophrenia. From a list of current clinic patients generated for each site, those patients without a recent acute relapse, within the

Patient characteristics

A total of 1433 patients were recruited into the Pattern study, from 140 study sites in eight countries (Argentina, Brazil, Canada, France, Germany, Italy, Spain and the United Kingdom). Overall, 1379 patients were included in the CS-PAS; 54 (3.8%) patients were excluded, the majority because they did not have a diagnosis of schizophrenia (primarily schizoaffective disorders). Socio-demographic information was similar across the eight countries (Table 2). Overall, patients were predominantly

Discussion

The cross-national characteristics of the Pattern study allowed comparison of various patient characteristics and outcome variables between countries, similar to recent investigations into psychopathological characteristics of patients with schizophrenia from Brazil, China and the US (Stefanovics et al., 2014). The data of more than 1300 patients and their family members or informal carers represent a valuable epidemiological contribution towards the study of schizophrenia. Clinically stable

Conclusion

This cross-sectional study of 1379 patients, and their carers represents a valuable real-world contribution to the study of schizophrenia, particularly given that naturalistic data from 140 centers across eight countries were collected. Based on this cross-sectional assessment, there was a high prevalence of patients with positive and/or negative persistent symptoms of schizophrenia and associated functional impairment. These results further substantiate the deleterious impact of persistent

Funding

This research was sponsored by F. Hoffmann-La Roche Ltd.

Author contributions

Josep Maria Haro contributed to development of all drafts of the manuscript and approved the final version.

Carlo Altamura contributed to the first draft of the manuscript and literature analyses and approved the final version.

Ricardo Corral recruited and evaluated patients, and contributed to and approved the final manuscript.

Helio Elkis reviewed and contributed to all versions of the manuscript and approved the final version.

Jonathan Evans recruited patients, discussed the analysis plan and

Conflicts of interest

Carlo Altamura has served as a consultant or advisory board member for F. Hoffmann-La Roche, Ltd., Lundbeck, Merck, Astra Zeneca, Bristol Myers Squibb, Janssen-Cilag, Sanofi, Eli Lilly, Pfizer and Otsuka. Helio Elkis has received research grants from the São Paulo Research Foundation (FAPESP), Janssen-Cilag and Roche, participated on advisory boards for Janssen-Cilag and Roche, and received honoraria and travel support from Janssen-Cilag and Roche. Ashok Malla has received honoraria or

Acknowledgments

The authors received medical editing support from inVentiv Medical Communications, which was funded by F. Hoffmann-La Roche Ltd. The authors would like to acknowledge Bridge Medical for their support in the development of the Pattern study protocol and to thank OXON Epidemiology for their support with the health economic aspect of the study. The authors would also like to thank all investigators, their site staff, and patients and their caregivers in the collection of these data.

References (54)

  • R. Tandon et al.

    Schizophrenia, “just the facts” what we know in 2008. Part 2. Epidemiology and etiology

    Schizophr. Res.

    (2008)
  • P. Uggerby et al.

    Characteristics and predictors of long-term institutionalization in patients with schizophrenia

    Schizophr. Res.

    (2011)
  • J. Van Os et al.

    Schizophrenia

    Lancet

    (2009)
  • N.C. Andreasen et al.

    Remission in schizophrenia: proposed criteria and rationale for consensus

    Am. J. Psychiatr.

    (2005)
  • J. Bobes et al.

    Prevalence of negative symptoms in outpatients with schizophrenia spectrum disorders treated with antipsychotics in routine clinical practice: findings from the CLAMORS study

    J. Clin. Psychiatry

    (2010)
  • J.S. Brekke et al.

    Cross-ethnic symptom differences in schizophrenia: the influence of culture and minority status

    Schizophr. Bull.

    (1997)
  • R.W. Buchanan

    Persistent negative symptoms in schizophrenia: an overview

    Schizophr. Bull.

    (2007)
  • A. Caspi et al.

    Treatment-refractory schizophrenia

    Dialogues Clin. Neurosci.

    (2004)
  • C.M. Cassidy et al.

    Testing definitions of symptom remission in first-episode psychosis for prediction of functional outcome at 2 years

    Schizophr. Bull.

    (2010)
  • M.H. Chakos et al.

    Baseline use of concomitant psychotropic medications to treat schizophrenia in the CATIE trial

    Psychiatr. Serv.

    (2006)
  • P. Chue et al.

    Addressing the unmet needs of patients with persistent negative symptoms of schizophrenia: emerging pharmacological treatment options

    Neuropsychiatr. Dis. Treat.

    (2014)
  • J.G. Csernansky et al.

    Relapse and rehospitalisation rates in patients with schizophrenia

    CNS Drugs

    (2002)
  • S. Doering et al.

    Predictors of relapse and rehospitalization in schizophrenia and schizoaffective disorder

    Schizophr. Bull.

    (1998)
  • R. Emsley et al.

    The concepts of remission and recovery in schizophrenia

    Curr. Opin. Psychiatry.

    (2011)
  • S.M. Erhart et al.

    Treatment of schizophrenia negative symptoms: future prospects

    Schizophr. Bull.

    (2006)
  • G. Fervaha et al.

    Motivational and neurocognitive deficits are central to the prediction of longitudinal functional outcome in schizophrenia

    Acta Psychiatr. Scand.

    (2014)
  • J.M. Haro et al.

    The European Schizophrenia Outpatient Health Outcomes Study: baseline findings across country and treatment

    Acta Psychiatr. Scand. Suppl.

    (2003)
  • Cited by (0)

    View full text