Rates and predictors of relapse following discontinuation of antipsychotic medication after a first episode of psychosis
Introduction
Antipsychotic medications are effective in treating the symptoms of psychotic disorders, especially positive symptoms (Leucht et al., 2009). With such treatment, symptomatic remission is achieved in as many as 80% of individuals affected by a first episode of psychosis (FEP) (Malhi et al., 2010). However, when used long-term, antipsychotic medications can carry 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., 2013). A 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). In recent years, significant questions have arisen around the necessity of long-term maintenance antipsychotic medication in this population (Murray et al., 2016).
Current clinical guidelines recommend maintenance medication for between a minimum of one to two years following remission after a FEP (Taylor et al., 2011). However, contrary to such guidelines, up to 70% of individuals disclose that they ceased their medications within less than twelve months of achieving 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 after clinical remission (Thompson et al., 2016).
Whilst long-term use of antipsychotic medications pose potential risks, so too does discontinuation. Relapse rates vary across studies, but are consistently higher amongst those who discontinue antipsychotic medication and are reduced with maintenance treatment (Zipursky et al., 2014). Some believe that relapse may hinder or reverse the 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 for the first episode (Lieberman et al., 1996). Yet, not all those who discontinue maintenance medication will experience relapse.
Considerable research exists with respect the factors predictive of relapse after a FEP. However, most studies have been conducted amongst individuals who remain on maintenance antipsychotic treatment (Diaz-Caneja et al., 2015). Importantly, predictive factors may differ between those who continue medication, and those who discontinue (Hui et al., 2013). At present, there is a paucity of information to guide clinicians in either supporting or advising against medication discontinuation after remission following a FEP.
A trial of discontinuation after remission is a common request, and following discontinuation, some individuals are able to sustain remission (Gaebel et al., 2016, Wunderink et al., 2007). In order to guide clinicians in pre-discontinuation counseling, there would be utility in being able to identify those individuals for whom either relapse or sustained remission is likely. As such, the present study is an analysis of the demographic and clinical predictors of relapse following discontinuation of antipsychotics after a FEP.
The study aimed to determine: i) the proportion of young people with a FEP who undergo at least one trial of discontinuation of their antipsychotic medication during their episode of care; ii) the proportion of those who discontinue their medication and experience a relapse of psychotic symptoms; and iii) the demographic and clinical predictors of relapse following a first trial of discontinuation.
Section snippets
Materials and methods
The study involved a retrospective study of an epidemiological cohort of 544 individuals who received treatment with the Early Psychosis Prevention and Intervention Centre (EPPIC) and were diagnosed with a FEP.
Context and setting
The EPPIC program offers a comprehensive service to young people aged 15 to 24 years experiencing a FEP. Treatment duration is an average of eighteen months and a maximum of twenty-four months (except for those under the age of 18, who can continue to receive service beyond two years until
Sample clinical and demographic characteristics
The cohort consisted of 544 individuals, 325 of whom (59.6%) were male. The mean age at service entry was 19.5 years (± 2.9). A first-degree relative with a psychotic disorder was reported by 122 individuals (20.6%), and a similar number (n = 107; 19.7%) had a second-degree relative with a psychotic disorder.
The median duration of the episode of care was 688 days (IQR 466–743). A diagnosis of non-affective psychosis was received by 353 individuals (64.9%), of which schizophreniform disorder was the
Discussion
Three main findings stem from this study. First, 61% of the cohort had at least one trial of discontinuation. Second, amongst individuals trialing discontinuation, 45.8% experienced a relapse within the follow-up period. Third, individuals with a history of poor compliance (trend association) and a diagnosis of cannabis abuse disorder may be more likely to experience relapse following discontinuation. Interestingly, results were non-predictive for amphetamine abuse. The reason for this is
Strengths and limitations
Findings from the present study must be interpreted in the context of several limitations. Potential predictors and outcome measures were assessed on the basis of retrospective clinical notations including mental status examinations. Such mental status examinations were used as the basis upon which to rate psychotic symptoms, and thus determine remission and relapse status. It is possible that documentation of symptoms was insufficient for full or accurate interpretation of the clinical
Conclusion
We have demonstrated that there may be a small number of predictive factors to guide clinicians in either supporting or advising against early discontinuation. Individuals with diagnosis of cannabis abuse may be more likely to experience relapse after a trial of discontinuation. A prolonged duration of antipsychotic medication may not reduce the risk of relapse post discontinuation, but relapse may be more likely amongst those who demonstrate non-compliance. Amongst individuals in whom
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.
The authors have no conflicts of interest.
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