Schizophrenia Bulletin Open

doi:10.1093/schizbullopen/sgaa017

Rates and Predictors of Relapse in First-Episode Psychosis: An Australian

Cohort Study

Ellie Brown*,1,2, , Gillinder Bedi1,2, Pat McGorry1,2, and Brian O’Donoghue1,2

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1
Orygen, Melbourne, Victoria, Australia; 2Centre for Youth Mental Health, University of Melbourne, Melbourne, Victoria, Australia
*To whom correspondence should be addressed; Orygen, 35 Poplar Road, Parkville, Melbourne, Victoria 3052, Australia; tel: +61 3 9966
9310, e-mail: Ellie.brown@unimelb.edu.au

Background: Clinical and functional recovery is usu- Introduction

ally achieved after treatment for a first episode of psy-
Early Intervention (EI) for psychosis services have been
chosis (FEP). Unfortunately, subsequent relapse remains
established internationally for individuals experiencing
common, occurring within a year for approximately
a first episode of psychosis (FEP). These services aim
30% of individuals and up to 80% over 5  years. Factors
to reduce delays in accessing services and specialized
that make relapse more likely in any given individual re-
treatments.1 However, using the term “first” could imply
main poorly understood.  Methods: This article presents
that a second episode of psychosis is likely. Indeed, for
a naturalistic cohort study of young people (15–24  years
a proportion, this is the case. More than half of people
old) accessing an early intervention in psychosis service
who experience 1 episode of psychosis will go on to ex-
in Melbourne, Australia between January 1, 2011 and
perience a further episode within 3  years, with the risk
December 31, 2016. Demographic and clinical predictors
of subsequent episodes increasing over time.2 Further
of relapse were collected and analyzed using Cox regression
relapses once individuals transition from EI to adult
analysis. Results: A total of 1220 young people presented
community mental health services are also common, typ-
with an FEP during the study period; 37.7% (N = 460) ex-
ically occurring for half of the individuals accessing these
perienced at least 1 relapse during their episode of care.
services.3 These rates highlight that for some people, there
Over half of all relapses resulted in an admission to hos-
can be a more enduring nature to psychotic disorders
pital. Non-adherence to medication, substance use, and
after remission and recovery from a first episode.4 This
psychosocial stressors were commonly noted as clinical
matters, as relapse during the first few years after ill-
precipitants of relapse. Significant predictors of relapse
ness onset is recognized as an important determinant of
(vs no relapse) were a diagnosis of schizophrenia spectrum
longer-term clinical and functional outcomes.5 Recovery
disorder (adjusted hazard ratio [aHR] = 1.62) or affective
can be slowed, and the course of illness worsened, with
psychotic disorder (aHR  =  1.37), lifetime amphetamine
each relapse.6 Relapse is also costly to both the individual
use (aHR = 1.48), and any substance use during treatment
and their caregivers, as well as the healthcare system.7,8
(aHR = 1.63). Conclusion: These findings suggest that re-
However, one recent study has challenged the link be-
lapse occurs frequently for young people who have expe-
tween relapse and poor longer-term outcomes, showing
rienced FEP. This is one of the first studies to report that
that individuals with lower exposure to antipsychotic
amphetamine use (predominantly illicit methamphetamine)
medication had better functional recovery despite higher
increases the risk of relapse. Clinical services, especially in
initial relapse rates.9 Still considering this, relapse preven-
Australasia, need to consider how best to manage this co-
tion should continue to be a critical focus of clinicians
morbidity in young people with FEP.
and academics working in the field of early psychosis.
Within this context, improving understanding of the
Key words:  first-episode psychosis/early intervention/rel factors that increase (or decrease) the risk of relapse is a
apse/rates/predictors clinically important goal.

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Page 1 of 9
E. Brown et al
While attempts have been made to understand factors
predicting relapse following FEP, there remains a lack of
clarity around such predictors. Authors of a 2012 meta-
analysis of risk factors for relapse2 identified 109 sepa-
rate predictors analyzed across 29 studies. Of note, only a
third of these studies had the primary aim of identifying
clinical predictors of relapse using comprehensive statis-
tical modeling (such as Cox regression analysis), and the
majority used inadequate sample sizes. Most reported re-
lapse as an additional outcome to the main focus of their
study. As a result of such methodological limitations,
only 24 predictors were assessed in 3 or more studies, and
data were able to be extracted and pooled in the meta-
analysis for only 10 predictors. From these, illicit sub-
stance use and medication non-adherence were the only
2 factors to show a consistent positive association with
relapse. Factors less consistently predictive of relapse in-
cluded duration of untreated psychosis (DUP) or illness
(DUI), and comorbid affective symptoms. Finally, di-
agnosis of non-affective psychosis, insight, positive psy-
chotic symptoms, negative symptoms, and alcohol abuse
were all found to have limited associations with relapse.
While providing some insight into individual differences
contributing to relapse likelihood, limitations in this body
of research suggest that rigorous studies of predictors of
relapse following an FEP from larger cohorts are required
to further inform the evidence base and clinical practice.
Subsequent studies to this meta-analysis have further
supported the evidence that medication adherence and
substance use are the most commonly associated factors
with relapse. Of note, these are potentially modifiable risk
factors.10–13
In addition to these known factors, there remains some
that are understudied, such as migration. Given that rates
of migration to Australia continue to grow, consideration
should be given to the impact of this factor on service
use and clinical outcomes. Thus, much remains unknown
about factors predicting whether individuals with psy-
chosis experience relapse. This current study aims to
determine the rate, frequency, and predictors of relapse
for a cohort of young people who have experienced an
FEP, with relapse examined during the time they were
under the care of a specialist early psychosis service in
Melbourne, Australia.
Methods
Setting
Orygen is a specialist mental health service based in the
North-Western area of Melbourne, Australia, for young
people aged between 15 and 24. The Early Psychosis
Prevention and Intervention Centre (EPPIC) service
within Orygen provides care to approximately 500 young
people with FEP at any one time from a geographically
defined catchment area of over 1 million residents.
Page 2 of 9
Participants
Participants include individuals who first attended the
EPPIC service between January 1, 2011 and December
31, 2016 experiencing a first episode of a psychotic dis-
order, operationalized as an individual having at least 1
positive psychotic symptom daily, for at least 1 hour, for
a duration of at least 1 week. This includes diagnoses of
schizophrenia, schizophreniform disorder, schizoaffective
disorder, substance-induced psychotic disorder, delu-
sional disorder, bipolar disorder with psychotic features,
major depressive disorder with psychotic features, brief
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psychotic disorder, and psychotic disorder not otherwise
specified (NOS). Young people with an FEP can attend
EPPIC for a period of 2  years, except those who were
aged under 16 at the time of presentation, who can have
an episode of care of longer than 2  years, lasting until
they reach the age of 18.
Inclusion Criteria
The inclusion criteria to the EPPIC service during this
period were (1) diagnosis of an FEP; (2) aged between 15
and 24 years at the time of presentation; and (3) residence
within the North-Western catchment area of Melbourne.
Individuals with comorbid substance use or substance
use disorders, comorbid personality disorders, and intel-
lectual disability were not excluded.
Design and Procedure
This is a naturalistic cohort study in which the data
were recorded prospectively but collected retrospectively
from clinical files. Demographic and clinical data were
extracted from clients’ paper files and electronic medical
records using a specifically designed audit tool.
Data Sources, Measures, and Definitions
Clinical Records..  Each client file contains information
compiled during the treatment period from sources in-
cluding initial assessment reports, outpatient notes, inpatient
notes (if applicable), clinical review meetings, and discharge
letters. Clinical information such as diagnosis at 3 months
and discharge, any hospital admissions, type and number of
antipsychotic medications prescribed, as well as episodes of
exacerbation and relapses were recorded. Diagnoses were
determined by the treating consultant psychiatrist.
Given the variety of diagnoses given to individuals
experiencing FEP, these were categorized into 3 groupings:
schizophrenia spectrum disorder (schizophrenia,
schizophreniform disorder, schizoaffective disorder); af-
fective disorder (bipolar disorder with psychotic features,
major depressive disorder with psychotic features); and
other psychotic disorder (substance-induced psychotic
disorder, delusional disorder, brief psychotic disorder,
and psychotic disorder not otherwise specified [NOS]).

Information was obtained for the duration of the
individuals’ treatment within the EI for Psychosis service.
Determination of Symptom Severity and Remission
The severity of psychotic symptoms was assessed and
rated at baseline, and at 3  monthly intervals thereafter.
Positive psychotic symptoms were rated as per the short
form SAPS.14 Routinely, case managers and psychiatrists
conduct and document mental state examinations in the
clinical notes.15 These were used as the basis from which
to assess and rate psychotic symptoms for this study
with researchers utilizing the SAPS. In addition, they
participated in inter-rater reliability testing through inde-
pendently completing 5 ratings performed across 5 indi-
vidual files. Remission was defined as positive symptoms
of severity ratings of less than or equal to 2 for at least
12 weeks. Participants could only be determined to have
experienced a relapse if they had achieved remission first.
Relapse
Relapse was defined as the return of symptoms based on
the clinician’s judgment of the participant having a re-
lapse and this being documented in the clinical notes as
such. Clinicians working within the EPPIC service follow
the Australian Clinical Guidelines for Early Psychosis,
within which the characteristics of relapse, and subse-
quent management, are considered in detail.
Data were also collated on the apparent precipitant of
relapse as assessed by the treating team and detailed in
the clinical notes. These were then categorized as being 1
or more of the following: non-adherence to medication,
substance use, psychosocial stressors, ineffective medica-
tion, or unknown. Finally, whether each relapse resulted
in hospitalization was recorded.
Predictor Variables
A number of demographic and clinical variables were
collected for analysis as potential statistical predictors
of relapse (vs no relapse). These included age, gender,
marital and living status, employment/education/training
status (those who were “not in education, employment
or training” are identified as “NEET”), family history of
psychotic disorders in a first or second-degree relative,
DUP, migration status, comorbid substance use, including
alcohol, amphetamine (referring here to “amphetamine-
type stimulants,” with the majority being illicit metham-
phetamine, ie, “ice” and speed), and cannabis use, and
substance misuse prior to presentation, at presentation
and during treatment. These specific factors were chosen
based both on previously identified predictors of relapse
as well as their availability in electronic medical records.
Rates and Predictors of Relapse in First-Episode Psychosis
Statistical Analysis
Data were analyzed using Statistical Package for Social
Sciences (SPSS) version 25 with descriptive statistics cal-
culated for 2 groups; those who did experience at least
1 relapse during their episode of care and those who
did not. The demographic and clinical predictors of re-
lapse were investigated using univariate and subsequent
multivariable Cox regression models. Univariate Cox
regression analysis was first performed on each poten-
tial predictor variable. Variables with P ≤ .10 were then
entered into a multivariate Cox regression model using
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the enter method. Where there were missing values in
the dataset, these individuals were excluded from the
analysis. This methodology allows the investigation of
the effect of several variables upon the time a specified
event takes to happen. Time to relapse was defined as the
number of days from first contact recorded with services
until the first date that relapse occurred. For those who
did not relapse, the last known date at which they had
not relapsed was used (ie, date of discharge), Cox regres-
sion analysis was used to determine hazard ratios (HRs)
and adjusted HRs (aHRs—in multivariate analysis) with
95% confidence intervals (CIs) for predictors of relapse.
An HR of 1 indicates the same relative risk of relapse
compared to the reference group (did not relapse), an HR
<1 indicates lower relative risk, and an HR >1 indicates
higher relative risk.
Ethical Approval
The present study was approved by the Royal Melbourne
Human Research and Ethics Committee as a quality as-
surance/audit project (reference: QA2018034).
Results
Demographics
A total of 1220 young people received treatment for an
FEP during the study period of 6 years. The demographic
and clinical characteristics of the total cohort, as well as
for individuals who relapsed and those who did not are
presented in table  1. The mean age at presentation was
19.6  years (±2.8), with the majority never married, and
two-thirds living with their parents. A  total of 42% of
the cohort had a diagnosis of “schizophrenia spectrum
disorder,” 22% had an “affective psychotic disorder” and
37% an “other psychotic disorder.” Comorbid substance
misuse (previous or current) was present in 61% of the
cohort, most commonly cannabis (52%) and ampheta-
mine (28%). Eighteen percent of the sample had a relative
with a history of psychosis, and 26% were a first-genera-
tion migrant. The mean time of follow-up was 83 weeks
(±34), and the median time was 93 weeks (IQR 62 to 106).
Page 3 of 9
Page 4 of 9
E. Brown et al

Table 1.  Clinical Demographics of the Sample, Including Those Who Did Relapse and Those Who Did Not

Total Sample (n = 1220) Relapsed (n = 460) Did not Relapse (n = 760)

Age (M ± SD, n = 1220) 19.6 ± 2.8 19.7 ± 2.8 19.5 ± 2.9

Male sex (N(%), n = 1220) 714 (58.5%) 291 (63.3 %) 423 (55.7%)
Never married (N(%), n = 1220) 1140 (93.4%) 435 (94.6%) 705 (92.8%)
Living with parents (N(%), n = 1220) 799 (65.5%) 333 (72.4%) 466 (61.3%)
Not in employment, education or training (NEET (N (%), n = 1206)) 563 (46.7%) 223 (51.1%) 330 (44.0%)
Family history of psychosis (N(%), n = 1220)
  First-degree relative 223 (18.3%) 96 (20.9%) 127 (16.7%)
  Second-degree relative 200 (16.4%) 89 (19.3%) 111 (14.6%)
Cultural background (N(%), n = 1220)
 Migrant 317 (26.0%) 111 (24.1%) 206 (27.1%)
  Identifies as Aboriginal or Torres Strait Islander (n = 1218) 34 (2.8%) 15 (3.3%) 19 (2.5%)
Diagnosis at baseline (N(%), n = 1220)
 Schizophrenia 210 (17.2%) 110 (23.9%) 100 (13.2%)
  Schizophreniform disorder 237 (19.4%) 93 (20.2%) 144 (18.9%)
  Schizoaffective disorder 64 (5.2%) 40 (8.7%) 24 (3.2%)
  Delusional disorder 17 (1.4%) 6 (1.3%) 11 (1.4%)
  Drug-induced psychosis 151 (12.4%) 52 (11.3%) 99 (13.0%)
  Bipolar affective disorder 153 (12.5%) 68 (14.8%) 85 (11.2%)
  Depression with psychosis 109 (8.9%) 26 (5.7%) 83 (10.9%)
  Psychotic disorder NOS 175 (14.3%) 43 (9.3%) 132 (17.4%)
  Brief psychotic disorder 28 (2.3%) 8 (1.7%) 20 (2.6%)
  Not differentiated 76 (6.2%) 14 (3.0%) 62 (8.2%)
Diagnostic groupings
  Schizophrenia spectrum disorder 511 (41.9%) 243 (52.8%) 268 (35.3%)
  Affective disorder 262 (21.5%) 94 (20.4%) 168 (22.1%)
  Other psychotic disorder 447 (36.6%) 123 (26.7%) 324 (42.6%)
Substance misuse (N(%), n = 1191)
  Any comorbid substance usea 721 (60.5%) 294 (64.9%) 427 (57.9%)
 Alcohol 210 (17.2%) 83 (18.0%) 127 (16.7%)
 Cannabis 635 (52.0%) 264 (57.4%) 371 (48.8%)
 Amphetamine 337 (27.6%) 161 (35.0%) 176 (23.2%)
Timing of substance use (N(%), n = 1187)
  Substance use prior to presentation 688 (58.0%) 283 (62.5%) 405 (55.2%)
  Substance use at presentation 471 (39.7%) 194 (42.8%) 277 (37.7%)
  Substance use during treatment 474 (39.9%) 233 (49.2%) 251 (34.2%)
  DUP (M ± SD, n = 1095) 39.7 ± 85.3 37.6 ± 83.2 40.9 ± 86.5

Note: NOS, not otherwise specified; DUP, duration of untreated psychosis.

a
Use refers to prior to or at presentation and/or during treatment.

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Relapse Rates
In total, 37.7% (n  =  460) of young people experienced
at least 1 relapse during their episode of care. Of these,
24.9% of the total cohort (n = 304) experienced 1 relapse,
8.4% (n = 106) experienced 2, 2.6% (n = 32) experienced
3, and 1.5% (n = 18) experienced 4 or more.
Relapse Precipitant and Consequence
Data on what clinicians’ thought was the proximal precip-
itant to a relapse were available for 453 out of 460 cases
of relapse (98.5%). Of these 453 cases, 26.9% (n = 122)
were recorded as precipitated by non-adherence to medi-
cation, 24.3% (n = 110) by non-adherence to medication
and substance use, 12.1% (n = 55) as precipitated by sub-
stance use alone, 13.5% (n = 61) by psychosocial stressors,
8.8% (n  =  40) by ineffective medication, 8.4% (n  =  38)
recorded as “unknown reason,” and 6.0% (n = 27) were
precipitated by substance use and psychosocial stressors.
Data on whether the first relapse resulted in hospitaliza-
tion or not were available for all but 9 young people (2.0%).
Of the remaining 451 cases, the first relapse resulted in hos-
pital admission for 58.5% (n = 269) of the cohort.
Predictors of Relapse
Univariate Cox Regression Analysis..  Several demo-
graphic and clinical characteristics at baseline were
found to predict subsequent relapse (P ≤ .10): age
(HR = 1.04), gender (HR = 1.31), NEET (HR = 1.32),
having a family history of psychosis in a second-degree
relative (HR = 1.24), diagnosis of a schizophrenia spec-
trum disorder (HR = 1.64) or affective psychotic disorder
(HR = 1.30), cannabis misuse (HR = 1.37), amphetamine
misuse (HR = 1.59), substance use prior to presentation
(HR = 1.39), substance use at presentation (HR = 1.24),
and substance use during treatment (HR = 1.61). The fol-
lowing predictors were not found to be predictors (P >
.10); living arrangements, family history of psychosis in
first-degree, migration status, DUP, and alcohol misuse,
these results can be seen in Table 2.
Multivariate Cox Regression Analysis..  Three independent
predictors of relapse were identified from the multivariate
Cox model analysis, see Table 2. The first was diagnosis:
young people who were diagnosed with a schizophrenia
spectrum disorder had a 1.62 increased risk of relapse
(aHR  =  1.62; 95% CI, 1.30–2.03; P < .0001) relative to
those with “other psychotic disorder,” and those with
affective disorder had 1.37 times higher risk of relapse
than those with “other psychotic disorder” (aHR = 1.37;
95% CI, 1.03–1.81; P < .03). Secondly, young people for
whom amphetamine misuse was reported had a 1.48 times
higher risk of relapse (aHR = 1.48; 95% CI, 1.18–1.86; P
< .001) compared to those who did not use amphetamines.
Finally, young people who reported substance use during
Rates and Predictors of Relapse in First-Episode Psychosis
treatment had a 1.63 times higher risk of relapse than
those who did not (aHR = 1.63; 95% CI, 1.23–2.17; P <
.001). Univariate factors that became nonsignificant in-
cluded; age, gender, NEET, having a family history of psy-
chosis in a second-degree relative, cannabis misuse, and
substance use prior to, and at presentation.
Discussion
The results of this cohort study examining rates and
predictors of relapse in young people with FEP con-
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firm and extend upon previous findings in the area. The
finding that 37.7% of the young people in our cohort ex-
perienced at least 1 relapse within their episode of care
is consistent with previous rates in first episode cohorts.2
Despite decades of service developments to promote an
integrated approach to care, clearly more needs to be
done by clinical services to have a meaningful effect on
this important metric.
Our finding that the most frequent precipitant of re-
lapse, as reported by clinicians, was non-adherence to
antipsychotic medication suggests that medication adher-
ence remains an integral part of ongoing recovery from
FEP, as it can be for a variety of clinical presentations.16
The frequency with which substance use and psychosocial
stressors were recorded as precipitants of relapse should
also be borne in mind when considering how services can
focus on decreasing rates of relapse. Whether a relapse
resulted in hospitalization was recorded, with over half
of the sample that relapsed requiring an admission.
Multivariate Cox regression analysis indicated that
there were 3 significant independent predictors of re-
lapse for this sample; diagnosis, amphetamine use, and
substance use (all) during treatment. Both diagnosis and
substance use disorder have been found to be significant
predictors of relapse in other multivariate analyses as
summarized in a meta-analysis of risk factors for relapse.2
The association between cannabis use and the develop-
ment of psychosis is now well established,17 as are the
adverse outcomes (including high relapse rates) of those
who continue to use cannabis after psychosis onset.18
Cannabis use was a significant predictor of relapse in our
univariate analysis; however, it did not emerge as a pre-
dictor in the multivariate analyses. These findings suggest
that in this cohort in Melbourne, Australia, amphetamine
use was overall a stronger predictor of relapse than other
illicit substances, including cannabis. This could be be-
cause the current sample had substantial polydrug use.
It is possible, and indeed likely, that the methampheta-
mine users in this cohort were heavier cannabis users
than those who smoked cannabis but did not use meth-
amphetamine, making it difficult to statistically dissociate
the relative contributions of each drug to relapse. While
not excluding potential contributions of cannabis use to
relapse, these findings do suggest that examination of
substance use beyond cannabis in relation to relapse in
Page 5 of 9
 Table 2.  Univariate and Multivariate Cox Regression Analysis of Predictors of Relapse

Univariate Cox Regression Model Multivariate Cox Regression Model

Page 6 of 9
Factor Unadjusted HR (95% CI) Wald P-value Unadjusted HR (95% CI) Wald P-value
E. Brown et al

Age 1.04 (0.99–1.08) 2.82 .09 NA .16

Sex
 Female 1 NA .26
 Male 1.31 (1.08–1.59) 7.36 .007
Living arrangements
  Not living with parents 1
  Living with parents 0.89 (0.72–1.10) 1.17 .28
Education/employment status
  In education/employment/training 1
 NEET 1.32 (1.09–1.59) 8.18 .004 NA .37
Family history in first-degree relative
 No 1
 Yes 0.87 (0.69–1.09) 1.51 .22
Family history in second-degree relative
 No 1
 Yes 1.24 (0.98–1.57) 3.26 .07 NA .12
Migration status
  Migrated to Australia 1
  Born in Australia 1.03 (0.83–1.29) 0.08 .77
Diagnosis
  Other psychotic disorder 1 1
  Schizophrenia Spectrum disorder 1.64 (1.31–2.05) 19.06 <.001 1.62 (1.30–2.03) 17.65 <.001
  Affective disorder 1.30 (0.99–1.72) 3.59 .06 1.37 (1.03–1.81) 4.83 .03
DUP 1.00 (0.99–1.00) 1.63 .20
Alcohol misuse
 No 1
 Yes 1.05 (0.83–1.34) 0.17 .68
Cannabis misuse
 No 1
 Yes 1.37 (1.14–1.66) 10.8 .001 NA .64
Amphetamine misuse
 No 1 1
 Yes 1.59 (1.31–1.93) 21.69 <.001 1.48 (1.17–1.86) 11.24 .005
Substance abuse prior to presentation
 No 1
 Yes 1.39 (1.15–1.69) 11.03 .001 .92
Substance abuse at presentation
 No 1
 Yes 1.24 (1.03–1.50) 5.09 .024 .10
Substance abuse during treatment
 No 1 1
 Yes 1.61 (1.33–1.94) 24.3 <.001 1.63 (1.23–2.17) 11.58 .001

Note: HR, hazard ratio; NOS, not otherwise specified; DUP, duration of untreated psychosis.

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FEP is a valuable direction for future research. This is
particularly pertinent in Australia, given there has been
a recognized increase in use of more potent smoked and
injected forms of methamphetamine (commonly known
as “ice” or “crystal meth”) and associated harms in
Australasia and South East Asia in the last 10 years.19,20
Acutely, methamphetamine intoxication can result in
transient psychotic-like symptoms in some individuals;
regular use is also associated with increased risk of psy-
chosis onset.21 The relationship between the use of this
drug, psychotic-like experiences, and a diagnosis of psy-
chosis that persists beyond drug clearance is no doubt
complex. It is unclear whether the association between
amphetamine use and psychosis is causal; it could be that
both psychosis and amphetamine use are expressions of
shared underlying vulnerabilities, or that psychosis prone-
ness predisposes towards amphetamine use. However,
given the known harms of amphetamine misuse even in
otherwise healthy groups,19,20 the finding that ampheta-
mine use is associated with an increased risk of relapse
in a cohort of young people experiencing early psychosis
suggests that a future focus of EI services, particularly in
Australasia, should be reducing comorbid methampheta-
mine use in young people with FEP.
While there are no established pharmacotherapies
for methamphetamine use disorder, a variety of can-
didate medications have been trialed, with some
showing promise in initial investigations.22 However,
some of these, such as agonist approaches using
psychostimulants, could have unacceptable risk-benefit
profiles in FEP populations. In the absence of safe
and efficacious pharmacotherapies for methampheta-
mine use, behavioral treatments, including cognitive-
behavioral therapy (CBT) and contingency management
(CM) remain the first-line treatments.23 However, the ex-
isting evidence base for these interventions remains lim-
ited,24 and cognitive impairments in FEP populations
may impact outcomes of CBT for methamphetamine
use given they can predict poor retention in treatment
in such trials.25 Moreover, recent evidence suggests that
CM did not reduce cannabis use in early psychosis, po-
tentially due to the specific reward protocol employed.26
Thus, to date, there is very limited evidence to guide
clinical intervention to reduce methamphetamine use in
early psychosis. The present findings indicate that clin-
ical research assessing the efficacy of pharmacological
and psychological approaches in FEP populations is
urgently needed.
Managing relapse rates more generally should also
remain a clinical and research priority. For example, in
a recent UK trial, Johnson and colleagues27 found that
delivering a peer-led self-management intervention signif-
icantly lowered relapse rates (by 9%). Adapting this type
of intervention for use by youth and family peer workers
within EI services may be one novel way of reducing
relapse rates.
Rates and Predictors of Relapse in First-Episode Psychosis
The univariate Cox Regression analysis highlighted
the relationship between not being in education, employ-
ment or training (NEET), and risk of relapse. While not
significant when combined with other predictors in the
multivariate analysis, this highlights both that NEET is a
common situation for individuals experiencing early psy-
chosis, and that it has an association with increased risk
of relapse. This finding replicates other studies in early
psychosis internationally.28–30 For nearly 20  years, there
has been growing concern that individuals with FEP are
far more likely to experience adverse economic, health,
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legal, and psychosocial outcomes.31,32 In Australia, the
proportion of individuals aged 15–24 who were NEET in
2017 was 11.8%.33 Our finding that 41.7% of our overall
sample were NEET and that it may be implicated in re-
lapse highlights the interplay between NEET status and
mental illness. As noted by Scott and colleagues’ edito-
rial,34 Government level “action plans” addressing this
issue can fail to recognize subgroups within the econom-
ically inactive population who are functionally impaired
because of evolving or preexisting mental illness. Findings
from cohort studies such as this current work provide evi-
dence of the need to challenge government strategies that
do not account for mental illness in NEET populations.
We found that migration status did not significantly
predict risk of relapse in our cohort. This suggests that
while migrants can be at a greater risk of experiencing
psychosis, once under the care of services, they are not
more likely to relapse than non-migrants. This goes
against beliefs often held by clinicians that this at-risk
population have worse outcomes. Further exploration of
outcomes in migrants experiencing psychosis is underway
to improve understanding of this growing population
within Australia.
Limitations
The file audit methodology employed here, while
allowing us to collect one of the largest samples to date
in studies on relapse predictors in early psychosis, also
had some limitations. The lack of a standardized defini-
tion of relapse remains an issue.2,35 However, given that
Alvarez-Jimenez and colleagues’ meta-analysis of relapse
predictors in early psychosis found that controlling for re-
lapse definition did not explain the heterogeneity of their
results, it is unlikely to have seriously impacted the current
results. Although the data were collected prospectively,
they were collated from clinical notes retrospectively.
The data quality was, therefore, dependent on clinical
record keeping. In addition, we did not have resources
to conduct an audit of the researchers auditing the clin-
ical notes (eg, double entering 10% of the data). Another
potential limitation is that the results for the precipitants
and consequence of relapse relied on researchers’ sub-
jective interpretation of the clinical notes. This means
that detailed standardized information about patterns of
Page 7 of 9
E. Brown et al
drug use were not available, nor was biochemical verifi-
cation of self-reported drug use. It also means that we
did not have data on medication compliance across the
complete dataset that could be used as a predictor in the
Cox regression modeling. A final limitation is that given
our naturalistic approach, we did not have a standardized
period of follow-up; therefore, we cannot totally exclude
the possibility that people lost to follow-up may also have
relapsed, thus affecting results. However, our current data
on duration of follow-up, in addition to previous findings
that the EPPIC service has high levels of re-engagement
of individuals that drop out of treatment,36 suggests that
young people were followed up for long enough to relapse
if they were going to.
Conclusions
In this cohort study of 1220 young people with FEP, we
found that 37.7% experienced at least 1 relapse within
their episode of EI care. This resulted in hospitalization
in over half of the sample, with non-adherence to medi-
cation being the most frequently reported proximal pre-
cipitant of relapse. Multivariate analysis revealed that
diagnosis and amphetamine use were significant unique
predictors of relapse occurrence in this sample. Given
that substance misuse during treatment, and in particular
amphetamine use is a modifiable factor, clinical services,
especially in regions with methamphetamine use issues,
need further, better-quality evidence to guide them to ef-
fectively manage this comorbidity in young people with
FEP.
Acknowledgment
The authors have declared that there are no conflicts of
interest in relation to the subject of this study.
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