Elsevier

Schizophrenia Research

Volume 197, July 2018, Pages 9-18
Schizophrenia Research

Clinical and demographic predictors of continuing remission or relapse following discontinuation of antipsychotic medication after a first episode of psychosis. A systematic review

https://doi.org/10.1016/j.schres.2017.11.010Get rights and content

Abstract

Background

Clinical guidelines recommend maintenance treatment with antipsychotic medication for one to two years following remission of symptoms after a first episode of psychosis. However, recent research has suggested that this may not be indicated. Consistent predictors of outcome would be beneficial to guide clinicians as to which individuals are likely to have a successful discontinuation.

Objectives

This study reviews the literature with the aim of identifying demographic and clinical predictors of either relapse or continued remission in those with a first episode of psychosis following discontinuation of antipsychotic medication.

Methodology

Data Sources: A systematic search of PubMed, CINAHL, and PsychInfo databases was performed. Eligibility Criteria: Cohort, case-control and clinical trials that were published in English, included participants with a first episode of psychosis, and examined clinical and demographic predictors of relapse or continued remission after antipsychotic discontinuation.

Results

Eleven studies fulfilled inclusion criteria. No positive findings were replicated across cohorts.

Predictors of relapse: male sex, unemployment, prior psychiatric admission, premorbid adjustment, childhood isolation, premorbid functioning, schizoid-schizotypal traits, schizophrenia diagnosis, concomitant medication, and more severe negative symptoms.

Some positive findings must be interpreted in the context of conflicting and replicated negative findings: sex, employment status, level of education, premorbid functioning, symptom severity, and schizophrenia diagnosis.

Other replicated non-predictive findings: age, ethnicity, marital status, family history, disorganized thoughts, affective symptoms, cannabis abuse, clinical global impression, social integration, duration and dose of antipsychotic treatment, and compliance.

Conclusion

No positive findings have been replicated across study cohorts. Non-predictive findings have been replicated.

Introduction

The first episode of psychosis (FEP) is a clinical presentation that warrants unique treatment guidelines; those affected are typically young, drug naïve, require lower doses of antipsychotic medication, and are more sensitive to side effects (Alvarez-Jimenez et al., 2016). Early intervention services provide treatment tailored to the needs of these individuals and such specialist services have now been established in multiple cities around the world. Many such programs provide care to individuals experiencing their first episode of either affective or non-affective psychotic disorders (Conus et al., 2017, Fusar-Poli et al., 2013a, Kane et al., 2016).

Antipsychotic medications are effective in treating the positive symptoms of psychotic disorders (Leucht et al., 2009). However, the long-term use of antipsychotic medications carries significant morbidity and mortality implications (Correll et al., 2009). Potential physical health complications include weight gain, dyslipidemia and diabetes, and possible structural brain changes (Fusar-Poli et al., 2013b). In the acute setting, early induction of an atypical antipsychotic at the minimum effective dose is the standard recommendation in most guidelines (Buchanan et al., 2010, Early-Pychosis-Guidelines-Working-Group, 2010, Taylor and Kapur, 2011). With antipsychotic treatment, symptomatic remission is achieved by as many as 80% of individuals affected by a FEP (Malhi et al., 2010). Following remission, most guidelines recommend maintenance treatment with an atypical antipsychotic medication at minimum effective dose, for a duration of one to two years (Taylor and Kapur, 2011).

However, more recently, the benefits of long-term maintenance treatment have been questioned, with there being a call for more research to guide treatment duration (Emsley et al., 2016, Moncrieff, 2015, Wunderink et al., 2013). Contrary to clinical guidelines, up to 70% of individuals disclose that they ceased their medications less than twelve months following remission (McEvoy et al., 2007). Interestingly, this practice appears to be supported by the majority of clinicians, with less than one third believing that antipsychotic medication should be continued for over a year post remission (Alvarez-Jimenez et al., 2016, Thompson et al., 2016).

Whilst there are risks associated with the long-term use of antipsychotic medication, there are also risks associated with discontinuation, as high relapse rates have been observed (Zipursky et al., 2014). Relapse may hinder or reverse gains made in social and vocational functioning whilst on maintenance treatment (Kam et al., 2015). There are also concerns that individuals may not respond as effectively to antipsychotic medication following relapse as in the first episode (Lieberman et al., 1996). Yet, not all those who discontinue antipsychotic medication will experience relapse. There would be clinical utility in being able to identify individuals who are likely to be able to discontinue antipsychotics and sustain remission after a FEP.

Considerable research has been undertaken to identify factors predictive of either relapse, or continuing remission amongst individuals who receive ongoing maintenance treatment. Commonly accepted predictors of relapse amongst such individuals are poor medication adherence, male sex, a longer duration of untreated psychosis (DUP), substance misuse, poorer premorbid adjustment, and a greater severity of negative symptoms at baseline (Alvarez-Jimenez et al., 2012). However, some have suggested that factors predictive of relapse or sustained remission may differ between those who continue medication, and those who discontinue (Hui et al., 2013). A key question is whether predictors of outcome amongst individuals receiving maintenance treatment are similarly predictive when applied to a discontinuation cohort.

As such, we aimed to conduct a systematic review of published reports that identified demographic and clinical predictors of outcome following antipsychotic discontinuation in individuals affected by a FEP. There is considerable heterogeneity amongst individuals cared for by specialist early psychosis services. Thus, an analysis of the total FEP cohort, including individuals affected by affective and non-affective psychoses, is necessary for clinical applicability and allows for inclusion of final diagnosis as a potential predictor. In this review, we specifically aimed to identify factors predictive of either continuing remission or of relapse. We also aimed to examine whether findings were replicated between studies.

Section snippets

Literature search

The study aimed to determine predictors and it was expected that multiple demographic and clinical variables would appear across studies. The following databases were systematically searched: PubMed, CINAHL, and PsychInfo. Ancestry searching was also conducted.

Keywords used

The search terms included: (determinant* OR predict*) AND (success* OR relapse OR fail OR recurrence OR outcome) AND (discontinu* OR cease OR stop OR cessation) AND (schizo* OR first episode OR psychosis) AND (antipsychotic OR

Results

Database searching yielded 1042 records. An additional two articles were identified through ancestry searching. After removal of duplicates, 783 articles remained. Following title screening, 578 articles were excluded. A review of abstracts excluded a further 138 articles. A total of sixty-four articles were reviewed in full, and a further fifty-three excluded. The process resulted in the identification of eleven articles (pertaining to ten cohort populations) for inclusion in the present

Rates of relapse

Within the present study, rates of relapse range from 19.4% to 97% across studies (Emsley et al., 2014, Emsley et al., 2012, Landolt et al., 2016). It is important to acknowledge that relapse rates reach high levels with long term follow up. However, research suggests that, even at a decade's follow up, not all individuals will experience relapse after a FEP, and many achieve prolonged periods of remission (Morgan et al., 2014). Further, with a lack of a uniform definition of relapse in the

Conflicts of interest

The authors have no conflicts of interest.

Role of the funding source

Professor PD McGorry is supported by a Research Fellowship from the National Health and Medical Research Council of Australia and is an NHMRC Senior Principal Research Fellow. Professor E Killackey is supported by a Career Development Fellowship from the National Health and Medical Research Council of Australia.

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