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The British Journal of Psychiatry (2017)

210, 342349. doi: 10.1192/bjp.bp.116.190058

Predictors and moderators of treatment outcome

in patients receiving multi-element psychosocial
intervention for early psychosis: results from the
GET UP pragmatic cluster randomised controlled
Antonio Lasalvia, Chiara Bonetto, Jacopo Lenzi, Paola Rucci, Laura Iozzino, Massimo Cellini,
Carla Comacchio, Doriana Cristofalo, Armando DAgostino, Giovanni de Girolamo, Katia De Santi,
Daniela Ghigi, Emanuela Leuci, Maurizio Miceli, Anna Meneghelli, Francesca Pileggi, Silvio Scarone,
Paolo Santonastaso, Stefano Torresani, Sarah Tosato, Angela Veronese, Angelo Fioritti, Mirella Ruggeri
and the GET UP Group*

The GET UP multi-element psychosocial intervention proved duration of untreated psychosis, premorbid adjustment and
to be superior to treatment as usual in improving outcomes insight predicted outcomes regardless of treatment. Only age
in patients with first-episode psychosis (FEP). However, to at first contact with the services proved to be a moderator
guide treatment decisions, information on which patients of treatment outcome (patients aged 535 years had greater
may benefit more from the intervention is warranted. improvement in psychopathology), thus suggesting that the
intervention is beneficial to a broad array of patients with
Aims FEP.
To identify patients characteristics associated with (a) a
better treatment response regardless of treatment type (non- Conclusions
specific predictors), and (b) a better response to the specific Except for patients aged over 35 years, no specific
treatment provided (moderators). subgroups benefit more from the multi-element psychosocial
Method intervention, suggesting that this intervention should be
Some demographic and clinical variables were selected recommended to all those with FEP seeking treatment in
a priori as potential predictors/moderators of outcomes at mental health services.
9 months. Outcomes were analysed in mixed-effects random
regression models. (Trial registration:, Declaration of interest
NCT01436331.) None.

Results Copyright and usage

Analyses were performed on 444 patients. Education, B The Royal College of Psychiatrists 2017.

Consistent evidence has been accumulated showing that early multi-element interventions could be delivered effectively in
interventions facilitate recovery and reduce long-term disability routine mental health services. Moreover, compared with patients
in patients with psychosis.1,2 Literature has also shown that early receiving routine care, those treated with the early multi-element
interventions should be provided on an integrated basis (i.e. interventions displayed greater reductions in overall symptom
multi-element) and be grounded in evidence-based psychosocial severity, and greater improvements in global functioning,
treatments.35 However, there is as yet no consensus on a service emotional well-being and the subjective burden of delusions.10
model for the provision of early interventions for patients with Overall, the study findings were consistent with those of a large
first-episode psychosis (FEP), nor do we know to what extent early trial conducted in the Recovery After an Initial Schizophrenia
intervention services are generalisable.68 The GET UP (Genetics, Episode (RAISE) initiative, which compared a comprehensive,
Endophenotypes, Treatment: Understanding early Psychosis) multidisciplinary, team-based treatment approach for FEP,
PIANO (Psychosis: early Intervention and Assessment of Needs designed for implementation in the USA healthcare system, with
and Outcome) trial9 was set up to fill this gap. It was designed routine community care (i.e. patients in the experimental arm
to assess early multi-element psychosocial interventions in experienced greater improvement in quality of life, psychopathology
epidemiologically representative samples of patients treated in and social functioning).11
routine generic mental health settings. A previous paper reported In the present study we sought to identify, among baseline
the feasibility and effectiveness of adding a multi-element psycho- demographic and clinical characteristics, predictors and moderators
social intervention to the standard treatment of patients with of treatment outcomes at 9 months. Existing literature provides
FEP. At 9-month follow-up it was clear, based on the retention some information on predictors of treatment outcome in patients
rates of patients and families in the experimental arm, that early with FEP.1217 Available data, however, are rarely based on
epidemiological samples compared with controls, and this
*The full list of authors included in the GET UP Group appears in the online increases the risk of underestimating the complexities of treating
supplement to this paper. FEP in real-world services.18 The present study attempted to deal

Predictors and moderators of treatment outcome for an early psychosis intervention

with this gap, and, in particular, aimed to understand: (a) which medication in the past 3 months, for an identical or similar mental
patients characteristics are associated with a better treatment disorder; (b) mental disorders because of a general medical
response, regardless of treatment type (non-specific predictors); condition; (c) moderate-severe intellectual disability diagnosis
and (b) which characteristics are associated with a better response assessed by a clinical functional assessment; and (d) diagnosis
to the specific FEP treatment provided in the GET UP trial other than ICD-10 for psychosis25 (with the exception of non-
(moderators). Predictors of outcome across treatment groups psychotic disorders comorbid with a primary diagnosis of
provide prognostic information by clarifying which patients will psychosis). All eligible patients who achieved clinical stabilisation
respond more favourably to treatment in general, whereas were invited to provide written informed consent for assessment.
treatment moderators provide prescriptive information about They were told of the nature, scope and possible consequences of
optimal treatment selection.19 Although there are clinical the trial and that they could withdraw consent at any time. They
benefits in establishing baseline predictors of overall treatment were also asked to give consent for family member assessments;
success,20 identifying treatment moderators (who will do better family members who agreed to participate provided written
in which treatment) may have more important clinical and cost- informed consent.
effectiveness implications. Despite the value of identifying the The specific ICD-10 codes for psychosis (F1x.4; F1x.5; F1x.7;
subgroups of patients and the circumstances associated with the F2029; F30.2, F31.2, F31.5, F31.6, F32.3, F33.3) were assigned
effectiveness of early multi-element psychosocial interventions at 9 months; the best-estimate ICD-10 diagnosis was made by
for psychosis, there is as yet little information about moderators consensus of a panel of clinicians taking into account all available
of outcome. These findings would be extremely relevant in order information on the time interval from patients intake by
to clarify generalisability issues of the experimental intervention completing the Item Group Checklist (IGC) of the Schedule for
effectiveness. The present study aims to fill this knowledge gap. Clinical Assessment in Neuropsychiatry (SCAN).26
Based on the existing literature, we hypothesised that, regardless
of treatment, symptomatic improvement at 9 months would be Treatments
poorer in men,12 and in people with an early age at onset,13 lower
The experimental treatment consisted of a multi-element psycho-
levels of education,16 a longer duration of untreated psychosis
social intervention, adjunctive to routine care. It included the
(DUP),11,21,22 poor premorbid functioning,12,15,16 poor insight,14
delivery of cognitivebehavioural therapy (CBT) for psychosis to
lower adherence to medication,23 diagnosis of non-affective
patients,27,28 and of psychosis-focused family intervention29 to
psychosis,24 and higher baseline symptom severity.12,15,16 Given the
families, together with case management30 involving both patients
lack of available information (with the exception of the DUP as
and their families. It was provided by CMHC staff, trained in the
reported by the RAISE study11), no specific a priori hypotheses
previous 6 months and supervised by experts. The intervention
could be made about moderators; thus, moderator analyses will be
began as soon as patients achieved clinical stabilisation (i.e. a
exploratory and use the same set of variables analysed as predictors.
condition in which they could collaborate in a brief clinical
Method examination). Core baseline measures were taken. Control arm
CMHCs provided only treatment as usual (TAU), which, in Italy,
The GET UP PIANO trial comprises personalised out-patient psychopharmacological treat-
The GET UP PIANO trial is a large multicentre randomised ment and non-specific supportive clinical management by the
controlled trial comparing an add-on multi-element psychosocial CMHC.31 Family interventions in TAU consisted of non-specific
early intervention with routine care for patients with FEP and informal support sessions.
their relatives provided within Italian public general mental
health services. Of the 126 community mental health centres Measures
(CMHCs) located in two northern Italian regions (Veneto and A set of core outcome instruments (Positive and Negative
Emilia-Romagna) and the urban areas of Florence, Milan and Syndrome Scale (PANSS),32 Global Assessment of Functioning
Bolzano, 117 (92.9%) participated, covering an area of 9 304 093 (GAF),33 Hamilton Rating Scale for Depression (HRSD)34) was
inhabitants. The assignment units (clusters) were the CMHCs, administered by a panel of 17 independent evaluators at baseline
and the units of observation and analysis were patients and their (after clinical stabilisation and before treatment was initiated) and
families. The trial received approval by the ethics committees of at 9-month follow-up. For the PANSS the three traditional sub-
the coordinating centre (Azienda Ospedaliera Universitaria scales were considered positive symptoms, negative symptoms
Integrata di Verona) and each participating unit and was and general psychopathology.
registered with (NCT01436331). Full details of An extensive set of standardised instruments was also
the protocol of the GET UP study and the main findings of the administered at baseline, including the Premorbid Social
GET UP PIANO trial can be found elsewhere.9,10 Adjustment scale (PSA)35 for premorbid functioning, the
Schedule for Assessment of Insight (SAI-E)36 for insight into
Participants illness and a modified version of the Nottingham Onset Schedule
During the index period, all CMHCs participating in the GET UP (NOS)37 for the DUP. These clinical measures, together with base-
PIANO trial were asked to refer individuals with potential cases of line sociodemographics (gender, age at first contact, citizenship,
psychosis at first contact to the study team. The inclusion criteria education) were analysed as putative predictors/moderators.
were: (a) age 1854 years; (b) residence within the catchment areas All the 17 independent evaluators were trained in the
of the CMHCs; (c) presence of at least one of the following administration and rating of the instruments. For the interrater
symptoms: hallucinations, delusions, qualitative speech disorder, reliability, each evaluator independently rated three videos on
qualitative psychomotor disorder, bizarre, or grossly inappropriate the PANSS, which were recorded and rated by an independent
behaviour; or two of the following symptoms: loss of interest, clinician. High levels of agreement (mean percentage agreement
initiative and drive; social withdrawal; episodic severe excitement; on the items of each scale) were reached between each evaluator
purposeless destructiveness; overwhelming fear; or marked self- and the clinician. Specifically, 85% for the positive scale, 70%
neglect; (d) first lifetime contact with CMHCs, prompted by these for the negative scale and 82% for the general scale. The intraclass
symptoms. Exclusion criteria were: (a) prescribed antipsychotic correlation coefficient was 0.81. Patients, clinicians and evaluators

Lasalvia et al

could not be masked to the trial arm. Every effort was made to significance of main effects), the variable was considered as a
preserve the evaluators independence; conflicts of interest were moderator. For each variable, the predictor and moderator effect
monitored. size was calculated using the formulae provided by Kraemer.39
In a secondary analysis, missing data on outcomes were
Statistical analyses estimated using a multiple imputation approach by chained
equations (MICE), which generates several different plausible
Analyses were conducted using an intention-to-treat (ITT) imputed data-sets and combines results from each of them. MICE
approach. PANSS, GAF and HRSD scores were analysed separately was applied because it allows one to handle different variable
in mixed-effects random regression models. In order to take into types; specifically, we used predictive mean matching to deal with
account the trial design in which patients (level 1) were nested possible non-normality when imputing continuous variables and
within CMHCs (level 2) (CONSORT guidelines for cluster logistic regression to impute binary variables. The alpha level
randomised trials38), the individual CMHCs were included in was set to 0.05 for all main effects and interactions. All statistical
the models as a random effect. In order to identify predictors analyses were carried out using the Stata software package,
and moderators of treatment outcome according to MacArthurs version 13.
approach,20 we selected a priori, on clinical or empirical grounds
and derived from the literature, a subset of demographic and
baseline clinical variables. Specifically, we investigated gender, Results
age at first contact, citizenship (Italian/non-Italian), educational
level (high/low), DUP, type of psychosis (affective/non-affective), Demographic and clinical variables of the 444 study participants
premorbid functioning (four components: school and social examined as potential predictors or moderators of treatment
functioning, in both childhood and adolescence) and insight into outcome are presented in online Table DS1.
illness (three components: attribution of symptoms, illness
awareness and treatment adherence). Each model included treat-
ment allocation (T coded as + for patients in the experimental Predictors
treatment group and 7 for those in the TAU group), one Some attributes of patients predicted outcomes regardless of
predictor/moderator (M standardised), their interaction (T6M) treatment assignment. Among sociodemographic characteristics
and the baseline score of the outcome investigated (B standardised). (Table 1), higher education predicted lower overall symptoms
When the main effect of a variable was significant but the interaction (b = 70.06, P = 0.034), negative symptoms (b = 70.11, P = 0.009)
was not, the variable was considered a non-specific predictor of and general psychopathology (b = 70.06, P = 0.046) at 9 months.
outcome. When the interaction was significant (regardless of the Several clinical characteristics predicted outcomes at 9 months

Table 1 Sociodemographic characteristics as potential predictors/moderators of treatment outcome a

b (95% CI), P r(DO, DM)b
Outcome at follow-up Interaction with treatment, Predictor Moderator
(adjusted for baseline) Main effect, prediction moderation effect size effect size

Age at first contact

PANSS total 0.04 (70.02 to 0.09), 0.157 70.12 (70.23 to 70.01), 0.032* 0.04 70.06
PANSS positive 70.00 (70.06 to 0.05), 0.889 70.07 (70.8 to 0.05), 0.238 0.00 70.03
PANSS negative 0.06 (70.02 to 0.14), 0.155 70.17 (70.34 to 70.01), 0.042* 0.04 70.06
PANSS general 0.06 (0.00 to 0.11), 0.039 70.14 (70.25 to 70.03), 0.014* 0.06 70.07
GAF score 70.44 (71.95 to 1.07), 0.570 70.13 (73.19 to 2.93), 0.934 70.02 0.00
HRSD score 0.34 (70.51 to 1.18), 0.432 70.13 (71.83 to 1.56), 0.878 0.02 0.00
Gender (reference men)
PANSS total 0.00 (70.05 to 0.06), 0.944 0.04 (70.07 to 0.14), 0.511 0.00 0.02
PANSS positive 0.04 (70.02 to 0.10), 0.179 0.04 (70.07 to 0.16), 0.438 0.03 0.02
PANSS negative 70.02 (70.10 to 0.07), 0.711 70.04 (70.21 to 0.12), 0.595 70.01 70.01
PANSS general 70.01 (70.06 to 0.05), 0.725 0.07 (70.04 to 0.18), 0.227 70.01 0.03
GAF score 70.94 (72.42 to 0.54), 0.213 0.30 (72.67 to 3.26), 0.845 70.03 0.01
HRSD score 0.50 (70.32 to 1.33), 0.229 0.46 (71.19 to 2.10), 0.588 0.03 0.01
Citizenship (reference Italian)
PANSS total 0.01 (70.04 to 0.06), 0.646 70.02 (70.13 to 0.08), 0.647 0.01 70.01
PANSS positive 0.02 (70.03 to 0.08), 0.460 70.04 (70.16 to 0.07), 0.429 0.02 70.02
PANSS negative 0.01 (70.07 to 0.09), 0.860 70.01 (70.17 to 0.15), 0.899 0.00 0.00
PANSS general 0.01 (70.04 to 0.06), 0.691 70.05 (70.15 to 0.06), 0.381 0.01 70.02
GAF score 0.19 (71.23 to 1.62), 0.791 0.79 (72.07 to 3.64), 0.589 0.01 0.01
HRSD score 0.26 (70.56 to 1.09), 0.529 0.10 (71.55 to 1.75), 0.906 0.02 0.00
Education (reference high level)
PANSS total 70.06 (70.12 to 70.00), 0.034* 70.00 (70.11 to 0.11), 0.996 70.06 0.00
PANSS positive 70.03 (70.09 to 0.02), 0.253 70.02 (70.13 to 0.10), 0.751 70.03 70.01
PANSS negative 70.11 (70.20 to 70.03), 0.009* 0.02 (70.15 to 0.19), 0.832 70.07 0.01
PANSS general 70.06 (70.11 to 70.00), 0.046 0.00 (70.11 to 0.11), 0.980 70.06 0.00
GAF score 1.47 (70.04 to 2.99), 0.057 0.48 (72.55 to 3.50), 0.758 0.05 0.01
HRSD score 70.65 (71.52 to 0.21), 0.136 0.65 (71.07 to 2.36), 0.461 70.04 0.02

PANSS, Positive and Negative Syndrome Scale; GAF, Global Assessment of Functioning; HRSD, Hamilton Rating Scale for Depression.
a. Mixed-effects random regression models estimated for patients who were assessed at both baseline and follow-up (experimental treatment group, n = 239; treatment-as-usual
group, n = 153).
b. See Kraemer for the calculation of predictor and moderator effect size.39
*Predictors/moderators that remained significant (P50.05) after applying multiple imputation procedure by chained equations (MICE).

Predictors and moderators of treatment outcome for an early psychosis intervention

(Table 2 and Table 3): specifically, a longer DUP predicted (PANSS negative score). A longer DUP predicted a greater severity
higher depressive symptoms (b = 1.42, P = 0.002); poorer of depression (b = 1.11, P = 0.005), and a poorer attribution of
premorbid social functioning in adolescence predicted higher symptoms predicted worse global functioning at follow-up
levels of overall psychotic symptoms (b = 0.07, P = 0.043) and (b = 2.14, P = 0.020).
depressive symptoms (b = 0.90, P = 0.039); and poorer premorbid
scholastic functioning in adolescence predicted higher negative Moderators
symptoms (b = 0.11, P = 0.035). Moreover, poorer attribution of We found a differential effect of age at first contact on PANSS total
symptoms predicted higher severity of overall psychotic symptoms score (b = 70.12, P = 0.032), negative symptoms (b = 70.17,
(b = 70.07, P = 0.036), higher levels of positive symptoms P = 0.042) and general psychopathology (b = 70.14, P = 0.014)
(b = 70.12, P = 0.003) and worse global functioning (b = 2.75, (Table 2). Specifically, the experimental treatment became more
P = 0.008); and poorer treatment adherence predicted higher level beneficial than TAU as age increased. When analyses were rerun
of overall psychotic symptoms (b = 70.08, P = 0.015), positive using multiple imputation of missing data, the finding that age
symptoms (b = 70.08, P = 0.017), negative symptoms (b = 70.11, at first contact was a moderator of PANSS total score
P = 0.031) and general psychopathology (b = 70.06, P = 0.045). (b = 70.11, P = 0.052), negative symptoms (b = 0.18, P = 0.032)
Multiple imputation analysis confirmed that lower education and general psychopathology (b = 70.12, P = 0.030) was confirmed.
predicted a higher severity of symptoms at follow-up (PANSS total In order to determine the age cut-off at which the experimental
score, b = 70.10, P = 0.016) and that a poorer attribution of treatment started to be significantly superior to TAU, age was
symptoms predicted a higher severity of positive symptoms categorised using different cut-offs (20, 25, 30, 35 years) in a
(PANSS positive score). Notably, lower educational level sensitivity analysis. This analysis showed that starting from
(b = 70.10, p = 0.016), poorer school performance in adolescence 35 years of age there was a significant treatment effect on PANSS
(b = 0.11, P = 0.022) and poorer treatment adherence (b = 70.10, (PANSS total: b = 70.12, P = 0.023, moderator effect size = 70.06;
P = 0.042) predicted a higher severity of negative symptoms PANSS negative: b = 70.18, P = 0.032, moderator effect

Table 2 Duration of untreated psychosis (DUP), insight (Schedule for Assessment of Insight (SAI)) and diagnosis as potential
predictors/moderators of treatment outcome a
b (95% CI), P r(DO, DM)b
Outcome at follow-up Interaction with treatment, Predictor Moderator
(adjusted for baseline) Main effect, prediction moderation effect size effect size

DUP (months)
PANSS total 0.04 (70.02 to 0.09), 0.171 0.00 (70.11 to 0.11), 0.967 0.04 0.00
PANSS positive 0.03 (70.03 to 0.09), 0.266 0.01 (70.11 to 0.13), 0.855 0.03 0.00
PANSS negative 0.08 (70.00 to 0.17), 0.055 0.01 (70.16 to 0.18), 0.927 0.05 0.00
PANSS general 0.03 (70.02 to 0.09), 0.267 0.00 (70.11 to 0.12), 0.978 0.03 0.00
GAF score 70.84 (72.46 to 0.77), 0.308 0.15 (73.04 to 3.34), 0.927 70.03 0.00
HRSD score 1.42 (0.53 to 2.31), 0.002* 70.83 (72.62 to 0.95), 0.361 0.08 70.03
SAI attribution of symptoms
PANSS total 70.07 (70.14 to 70.00), 0.036 70.04 (70.18 to 0.09), 0.538 70.08 70.02
PANSS positive 70.12 (70.20 to 70.04), 0.003* 70.06 (70.21 to 0.09), 0.447 70.11 70.03
PANSS negative 70.09 (70.19 to 0.01), 0.084 70.16 (70.36 to 0.04), 0.120 70.06 70.06
PANSS general 70.06 (70.13 to 0.01), 0.108 70.01 (70.14 to 0.13), 0.919 70.06 0.00
GAF score 2.75 (0.71 to 4.80), 0.008* 72.08 (75.98 to 1.82), 0.297 0.10 70.04
HRSD score 70.87 (71.75 to 0.00), 0.051 0.10 (71.64 to 1.84), 0.910 70.07 0.00
SAI illness awareness
PANSS total 0.02 (70.07 to 0.10), 0.711 0.10 (70.06 to 0.26), 0.231 0.02 0.06
PANSS positive 70.02 (70.10 to 0.07), 0.668 0.02 (70.16 to 0.19), 0.852 70.02 0.01
PANSS negative 0.04 (70.08 to 0.17), 0.471 0.08 (70.17 to 0.32), 0.534 0.04 0.03
PANSS general 0.01 (70.07 to 0.09), 0.865 0.13 (70.04 to 0.29), 0.125 0.01 0.07
GAF score 70.29 (72.72 to 2.14), 0.815 72.17 (77.17 to 2.83), 0.394 70.01 70.04
HRSD score 70.11 (71.27 to 1.05), 0.858 2.32 (0.02 to 4.62), 0.048 70.01 0.09
SAI treatment adherence
PANSS total 70.08 (70.14 to 70.02), 0.015 70.07 (70.20 to 0.05), 0.268 70.08 70.04
PANSS positive 70.08 (70.15 to 70.01), 0.017 70.07 (70.20 to 0.06), 0.312 70.08 70.03
PANSS negative 70.11 (70.21 to 70.01), 0.031* 70.11 (70.31 to 0.08), 0.265 70.07 70.04
PANSS general 70.06 (70.13 to 70.00), 0.045 70.07 (70.19 to 0.06), 0.285 70.07 70.04
GAF score 1.30 (70.56 to 3.16), 0.170 1.75 (71.88 to 5.38), 0.344 0.05 0.03
HRSD score 70.51 (71.32 to 0.29), 0.212 70.72 (72.34 to 0.89), 0.381 70.04 70.03
Type of psychosis (reference affective)
PANSS total 0.02 (70.04 to 0.07), 0.558 70.02 (70.14 to 0.09), 0.659 0.02 70.01
PANSS positive 0.03 (70.03 to 0.08), 0.310 70.02 (70.13 to 0.10), 0.763 0.03 70.01
PANSS negative 0.02 (70.06 to 0.10), 0.645 70.06 (70.23 to 0.11), 0.471 0.01 70.02
PANSS general 0.01 (70.04 to 0.07), 0.631 70.02 (70.13 to 0.10), 0.779 0.01 70.01
GAF score 71.38 (72.92 to 0.15), 0.077 70.15 (73.18 to 2.88), 0.922 70.05 0.00
HRSD score 0.47 (70.35 to 1.30), 0.261 70.88 (72.54 to 0.77), 0.296 0.03 70.03

PANSS, Positive and Negative Syndrome Scale; GAF, Global Assessment of Functioning; HRSD, Hamilton Rating Scale for Depression.
a. Mixed-effects random regression models estimated for patients who were assessed at both baseline and follow-up (experimental treatment group, n = 239; treatment-as-usual
group, n = 153).
b. See Kraemer for the calculation of predictor and moderator effect size.39
*Predictors/moderators that remained significant (P50.05) after applying multiple imputation procedure by chained equations (MICE).

Lasalvia et al

Table 3 Premorbid social adjustment (PSA) scale as potential predictor/moderator of treatment outcome a
b (95% CI), P r(DO, DM)b
Outcome at follow-up Interaction with treatment, Predictor Moderator
(adjusted for baseline) Main effect, prediction moderation effect size effect size

PSA social childhood

PANSS total 70.01 (70.08 to 0.06), 0.790 0.07 (70.06 to 0.21), 0.279 70.01 0.04
PANSS positive 70.01 (70.08 to 0.05), 0.694 0.07 (70.06 to 0.20), 0.300 70.01 0.04
PANSS negative 70.02 (70.13 to 0.08), 0.656 0.18 (70.02 to 0.39), 0.083 70.02 0.06
PANSS general 0.00 (70.06 to 0.07), 0.892 0.04 (70.10 to 0.17), 0.599 0.00 0.02
GAF score 70.01 (71.96 to 1.93), 0.990 71.75 (75.63 to 2.13), 0.376 0.00 70.03
HRSD score 0.27 (70.59 to 1.13), 0.534 0.68 (71.03 to 2.39), 0.436 0.02 0.03
PSA school childhood
PANSS total 0.05 (70.02 to 0.12), 0.132 70.02 (70.16 to 0.12), 0.759 0.06 70.01
PANSS positive 0.05 (70.02 to 0.11), 0.154 0.01 (70.12 to 0.14), 0.881 0.05 0.01
PANSS negative 0.07 (70.04 to 0.18), 0.196 70.09 (70.30 to 0.12), 0.396 0.05 70.03
PANSS general 0.05 (70.02 to 0.12), 0.149 70.01 (70.15 to 0.13), 0.888 0.05 70.01
GAF score 71.85 (73.83 to 0.14), 0.069 1.35 (72.59 to 5.28), 0.503 70.06 0.02
HRSD score 0.79 (70.08 to 1.66), 0.076 70.12 (71.87 to 1.62), 0.890 0.06 70.01
PSA social adolescence
PANSS total 0.07 (0.00 to 0.14), 0.043 0.01 (70.12 to 0.15), 0.851 0.07 0.01
PANSS positive 0.04 (70.03 to 0.11), 0.246 70.05 (70.18 to 0.08), 0.463 0.04 70.03
PANSS negative 0.10 (70.00 to 0.21), 0.063 0.08 (70.13 to 0.28), 0.473 0.07 0.03
PANSS general 0.06 (70.00 to 0.13), 0.063 0.01 (70.13 to 0.14), 0.915 0.07 0.00
GAF score 71.24 (73.18 to 0.71), 0.212 72.27 (76.09 to 1.56), 0.246 70.04 70.04
HRSD score 0.90 (0.05 to 1.76), 0.039 70.74 (72.44 to 0.96), 0.395 0.07 70.03
PSA school adolescence
PANSS total 0.05 (70.02 to 0.12), 0.169 0.02 (70.11 to 0.16), 0.729 0.05 0.01
PANSS positive 0.04 (70.03 to 0.10), 0.276 0.06 (70.07 to 0.19), 0.349 0.04 0.03
PANSS negative 0.11 (0.01 to 0.22), 0.035* 70.10 (70.31 to 0.11), 0.366 0.07 70.03
PANSS general 0.03 (70.04 to 0.10), 0.407 0.06 (70.07 to 0.20), 0.359 0.03 0.03
GAF score 71.67 (73.63 to 0.29), 0.094 1.49 (72.41 to 5.40), 0.453 70.06 0.03
HRSD score 0.77 (70.08 to 1.63), 0.077 0.74 (70.97 to 2.45), 0.397 0.06 0.03

PANSS, Positive and Negative Syndrome Scale; GAF, Global Assessment of Functioning; HRSD, Hamilton Rating Scale for Depression.
a. Mixed-effects random regression models estimated for patients who were assessed at both baseline and follow-up (experimental treatment group, n = 239; treatment-as-usual
group, n = 153).
b. See Kraemer for the calculation of predictor and moderator effect size.39
*Predictors/moderators that remained significant (P50.05) after applying multiple imputation procedure by chained equations (MICE).

size = 70.06; PANSS general: b = 70.13, P = 0.015, moderator experienced some benefit from both treatments, with a higher
effect size = 70.07) (Fig. 1). beneficial effect of experimental treatment in terms of reduction
Table 4 (lower part) shows that in the TAU arm patients in PANSS total, negative and general scores.
with an age of onset 535 years experienced no reduction of These findings were confirmed after multiple imputation of
overall psychotic symptoms, negative symptoms and general missing data (results not shown). In order to identify possible
psychopathology at 9 months (see delta scores), whereas patients reasons for this finding, we carried out secondary analyses comparing
with an age of onset less than 35 years (Table 4, upper part) patients with an age of onset 535 years with the rest of the sample.
Results indicate that patients with age at onset 535 years were
Table 4 Strength of moderation by patients age at first
more often females (41.0% v. 67.0%, w2 test, P50.001), less frequently
contact (535 years, 535 years) on the effect of intervention diagnosed with schizophrenia (19.4% v. 30.7%, w2 test, P = 0.033),
(experimental v. treatment as usual) on the various outcome less frequently unmarried (37.9% v. 91.3%, w2 test, P50.001) and
domains unemployed or students (46.6% v. 70.4%, w2 test, P50.001).
Delta, mean Finally, we found that a greater awareness of illness was
Outcome Treatment-as-usual group Experimental group
associated with a higher severity of depression at follow-up in
the experimental group but not in the control group (b = 2.32,
535 years P = 0.048) (Table 2); this finding, however, was not confirmed in
GAF 15.2 (14.9) 19.4 (16.6)
multiple imputation analysis (b = 0.38, P = 0.736). No moderation
PANSS positive 70.68 (0.81) 70.77 (0.81)
PANSS negative 70.68 (1.02) 70.67 (1.00)
was found for GAF and HRSD.
PANSS general 70.56 (0.70) 70.66 (0.73)
PANSS total score 70.63 (0.68) 70.69 (0.70) Discussion
HRSD 75.8 (13.3) 78.8 (1.0)
535 years This is the first study to investigate in a real-world setting which
GAF 13.0 (12.8) 18.3 (16.6) patient characteristics: (a) predict outcome regardless of treatment
PANSS positive 70.71 (0.78) 70.95 (0.72) assignment (non-specific predictors), and (b) moderate differential
PANSS negative 70.21 (0.69) 70.58 (0.93) response (moderators) to an adjunctive multi-element psychosocial
PANSS general 70.33 (0.51) 70.65 (0.60) intervention supplementing routine care for FEP. It used a large
PANSS total score 70.41 (0.48) 70.70 (0.56)
sample and a robust methodological approach.
HRSD 76.7 (13.0) 77.0 (10.2)
As expected, we found several non-specific predictors of
GAF, Global Assessment of Functioning; PANSS, Positive and Negative Syndrome outcome. Patients with lower education, longer DUP, poorer
Scale; HRSD, Hamilton Rating Scale for Depression.
premorbid functioning in adolescence and poorer insight into

Predictors and moderators of treatment outcome for an early psychosis intervention

3 3
2.8 535 years 2.8 535 years
2.6 TAU 2.6 TAU
2.4 2.4
2.2 EXP 2.2 EXP

2 2
1.8 1.8
1.6 1.6
1.4 1.4
1.2 1.2
1 1
Baseline Follow-up Baseline Follow-up

3 3
535 years 535 years
2.8 2.8
2.6 TAU 2.6 TAU
2.4 EXP 2.4 EXP

2.2 2.2
2 2
1.8 1.8
1.6 1.6
1.4 1.4
1.2 1.2
1 1
Baseline Follow-up Baseline Follow-up

3 3
535 years 535 years
2.8 2.8
2.6 TAU 2.6 TAU
2.4 EXP 2.4 EXP
2.2 2.2

2 2
1.8 1.8
1.6 1.6
1.4 1.4
1.2 1.2
1 1
Baseline Follow-up Baseline Follow-up

Fig. 1 Strength of moderation by patients age at first contact on the effect of the intervention (experimental EXP) v. treatment-as-usual
(TAU) group) on the Positive and Negative Syndrome Scale (PANSS).
Left-hand graphs 535 years at first contact, right-hand graphs: 535 years at first contact. (a) Total score; (b) negative symptoms; (c) general psychopathology. Mean scores
are reported on the y-axis; 1, absent; 2, minimal; 3, mild; 4, moderate; 5, moderate-severe; 6, severe; 7, extremely severe).

illness showed poorer clinical outcomes at 9 months irrespective It is not completely clear what drives the relationship between
of the type of treatment. These findings are consistent with the age at first contact and experimental treatment outcome in our
literature1117,2023 and suggest that patients with FEP with these sample. However, data showing that patients with age at onset
characteristics warrant specific attention and may require more 535 years were more often women, less frequently diagnosed with
intensive and/or longer treatment. schizophrenia, less frequently unmarried and unemployed or a
We found only one significant moderator that acted only on one student may in part explain the moderating effect of age at first
outcome: patients age at first service contact, which operated on contact on treatment outcome in our sample. We may also
negative symptoms and general psychopathology. Specifically, in speculate that patients developing psychosis at a later stage may
the control group, where the effect of the intervention was overall be more receptive to structured cognitive coping strategies
lower than in the experimental group, the moderation effect by age provided with both individual CBT and family therapy, since these
at first service contact resulted in lower benefit in older compared with patients have been found to be less impaired than younger
younger patients. Thus, the experimental intervention was not only patients on a broad array of cognitive tasks,4245 which are most
overall significantly more effective than TAU, but was also similar in relevant to adaptive functioning and treatment response. This issue
both age groups, showing greater generalisability. has some interesting implications, since the idea of intervening early
The multi-element psychosocial intervention administered at should not be conflated with intervening in the young, as psychosis
the first psychotic episode seems to exert a specific additional has an impact at all stages of life. A new line of research is specifically
beneficial effect on patients who develop onset of psychosis at a focusing on people over 35 years presenting to mental health services
later stage (535 years); these patients, if treated with usual care with a first psychotic episode. This research found that a large
alone, would display no or low symptomatic improvement. proportion (55%) of patients with FEP present after the age of
Moreover, it is important to note that the multi-component 25 years46 and suggested extending early intervention provision
intervention showed a specific beneficial effect on negative to all ages, with treatment tailored to the specific needs of different
symptoms, which in general show relatively poorer response to age groups.47,48 However, future research should further investigate
psychopharmacological treatment in patients with FEP.40,41 the relationship between age and outcome in FEP samples.

Lasalvia et al

Overall, the lack of significant moderators of treatment out-

comes suggests that the effects of the experimental intervention do
not vary according to patient baseline characteristics and that its Ministry of Health, Italy Ricerca Sanitaria Finalizzata, Code H61J08000200001.
beneficial effect is generalisable to the overall study population.
The fact that (apart from patients 535 years) no specific subgroups
benefit more from the experimental intervention indicates that early
multi-element psychosocial intervention should be recommended to We are grateful to the patients and their family members who participated in this study.
all patients with FEP treated in routine mental health services.

Study limitations References

Our moderator analyses should be considered as exploratory, 1 Penn DL, Waldheter EJ, Perkins DO, Mueser KT, Lieberman JA. Psychosocial
being aimed at providing useful information for designing future treatment for first-episode psychosis: a research update. Am J Psychiatry
clinical studies. The effect size of the moderators identified in the 2005; 162: 22202.

present paper may serve as guidance to researchers for estimating 2 Marshall M, Rathbone J. Early intervention for psychosis. Cochrane Database
Syst Rev 2011; 6: CD004718.
the sample size needed in confirmation studies. In order to test
3 Nordentoft M, Rasmussen JO, Melau M, Hjorthoj CR, Thorup AA. How
hypotheses on moderating effects, confirmatory studies would successful are first episode programs? A review of the evidence for
be needed, including an adequately sized group of patients with specialized assertive early intervention. Curr Opin Psychiatry 2014; 27:
the characteristics of interest (for example, age 535 years), in 16772.
which the outcomes of patients receiving different treatments 4 Orygen Youth Health. The Australian Clinical Guidelines for Early Psychosis.
(i.e. TAU v. GET UP intervention) are compared. Orygen Youth Health, 2008.

Another potential limitation is the lack of masking in the trial 5 National Collaborating Centre for Mental Health. Schizophrenia: Core
Interventions in the Treatment and Management of Schizophrenia in Primary
(patients, clinicians, other care providers and outcome evaluators and Secondary Care (update), NICE Clinical Guidelines, No. 82. NICE, 2009.
were aware of treatment allocation). The study design (cluster) 6 Singh SP, Fisher HL. Early intervention in psychosis: obstacles and
and the nature of the treatments under investigation did not permit opportunities. Adv Psychiatr Treat 2005; 11: 718.
masking. This limitation is inevitable and common to many cluster 7 Friis S. Early specialised treatment for first-episode psychosis: does it make a
randomised trials investigating the effects of psychosocial inter- difference? Br J Psychiatry 2010; 196: 33940.
ventions provided in routine care.49 However, we tried to reduce 8 Castle DJ. Should early psychosis intervention be the focus for mental health
the possible bias of unmasked outcome assessment by employing services? Adv Psychiatr Treat 2011; 17: 398400.

evaluators who were independent from the research team and who 9 Ruggeri M, Bonetto C, Lasalvia A, De Girolamo G, Fioritti A, Rucci P, et al.
A multi-element psychosocial intervention for early psychosis (GET UP PIANO
were not involved in treatment provision; every effort was also TRIAL) conducted in a catchment area of 10 million inhabitants: study
made throughout the trial to preserve the outcome evaluators protocol for a pragmatic cluster randomized controlled trial. Trials 2012;
independence; conflicts of interest were also monitored. 13: 73.
10 Ruggeri M, Bonetto C, Lasalvia A, Fioritti A, de Girolamo G, Santonastaso P,
Further research et al. Feasibility and effectiveness of a multi-element psychosocial
intervention for first-episode psychosis: results from the cluster-randomized
Our findings provide evidence that the GET UP multi-element controlled GET UP PIANO trial in a catchment area of 10 million inhabitants.
psychosocial intervention is beneficial to a broad array of patients Schizophr Bull 2015; 4: 1192203.
with FEP treated within routine community mental health 11 Kane JM, Robinson DG, Schooler NR, Mueser KT, Penn DL, Rosenheck RA,
services, and especially among those over 35 years of age. Further et al. Comprehensive versus usual community care for first-episode
psychosis: 2-year outcomes from the NIMH RAISE early treatment program.
studies in other geographical contexts and with longer-term Am J Psychiatry 2016; 173: 36272.
outcomes are needed to replicate and extend our findings. 12 Crespo-Facorro B, de la Foz VO, Ayesa-Arriola R, Perez-Iglesias R, Mata I,
Suarez-Pinilla P, et al. Prediction of acute clinical response following a first
Antonio Lasalvia, MD PhD, UOC Psichiatria, Azienda Ospedaliera Universitaria
episode of non affective psychosis: results of a cohort of 375 patients from
Integrata (AOUI), Verona; Chiara Bonetto, PhD, Department of Neurosciences,
Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona,
the Spanish PAFIP study. Prog Neuropsychopharmacol Biol Psychiatry 2013;
Verona; Jacopo Lenzi, PhD, Paola Rucci, PhD, Department of Biomedical and 44: 1627.
Neuromotor Sciences, Alma Mater Studiorum, University of Bologna, Bologna; Laura 13 Harrington E, Neffgen M, Sasalu P, Sehgal T, Woolley J. Initial predictors of
Iozzino, Department of Neurosciences, Biomedicine and Movement Sciences, Section
outcome in an early intervention in psychosis service. Early Interv Psychiatry
of Psychiatry, University of Verona, Verona; Massimo Cellini, Department of Mental
2013; 7: 3114
Health, Az. USL Firenze, Firenze; Carla Comacchio, MD, Doriana Cristofalo,
Department of Neurosciences, Biomedicine and Movement Sciences, Section of 14 Berge D, Mane A, Salgado P, Cortizo R, Garnier C, Gomez L, et al. Predictors
Psychiatry, University of Verona, Verona; Armando DAgostino, MD, Department of of relapse and functioning in first-episode psychosis: a two-year follow-up
Psychiatry, University of Milano, Milano; Giovanni de Girolamo, MD, IRCSS St John study. Psychiatr Serv 2016; 67: 22733.
of God Clinical Research Centre of Brescia, Brescia; Katia De Santi, MD, UOC
Psichiatria, Azienda Ospedaliera Universitaria Integrata (AOUI), Verona; Daniela Ghigi, 15 Albert N, Bertelsen M, Thorup A, Petersen L, Jeppesen P, Le Quack P, et al.
MD, Department of Mental Health, Az. USL Rimini, Rimini; Emanuela Leuci, MD, Predictors of recovery from psychosis. Analyses of clinical and social factors
Department of Mental Health, Az. USL Parma; Maurizio Miceli, MD, Department of associated with recovery among patients with first-episode psychosis after
Mental Health, Az. USL Firenze, Firenze; Anna Meneghelli, AO Ospedale Niguarda Ca 5 years. Schizophr Res 2011; 125: 25766.
Granda Milano, MHD Programma2000, Milan; Francesca Pileggi, MD, Department
of Mental Health, Az. USL Bologna, Bologna; Silvio Scarone, MD, Department of 16 Allott K, Alvarez-Jimenez M, Killackey EJ, Bendall S, McGorry PD, Jackson HJ.
Psychiatry, University of Milano, Milano; Paolo Santonastaso, MD, Department of Patient predictors of symptom and functional outcome following cognitive
Neurosciences, University of Padova and Azienda Ospedaliera, Padova; Stefano behaviour therapy or befriending in first-episode psychosis. Schizophr Res
Torresani, MD, Department of Mental Health, Az. USL Bolzano, Bolzano; Sarah Tosato, 2011; 132: 12530.
MD, PhD, Department of Neurosciences, Biomedicine and Movement Sciences, Section
of Psychiatry, University of Verona, Verona; Angela Veronese, MD, Department of 17 Schimmelmann BG, Huber CG, Lambert M, Cotton S, McGorry PD, Conus P.
Neurosciences, University of Padova and Azienda Ospedaliera, Padova; Angelo Fioritti, Impact of duration of untreated psychosis on pre-treatment, baseline, and
MD, Department of Mental Health, Az.USL Bologna, Bologna; Mirella Ruggeri, MD, outcome characteristics in an epidemiological first-episode psychosis cohort.
UOC Psichiatria, Azienda Ospedaliera Universitaria Integrata (AOUI), Verona and J Psychiatr Res 2008; 42: 98290.
Department of Neurosciences, Biomedicine and Movement Sciences, Section of
Psychiatry, University of Verona, Verona, Italy 18 Ruggeri M, Lasalvia A, Bonetto C. A new generation of pragmatic trials
of psychosocial interventions is needed. Epidemiol Psychiatr Sci 2013; 22:
Correspondence: Antonio Lasalvia, U.O.C. Psichiatria, Azienda Ospedaliera 1117.
Universitaria Integrata (AOUI), Policlinico G.B. Rossi, P.le Scuro, 10 37134
Verona, Italy. Email:
19 Wolitzky-Taylor KB, Arch JJ, Rosenfield D, Craske MG. Moderators and
non-specific predictors of treatment outcome for anxiety disorders:
First received 4 Jul 2016, final revision 15 Nov 2016, accepted 19 Dec 2016 a comparison of cognitive behavioral therapy to acceptance and
commitment therapy. J Consult Clin Psychol 2012; 80: 78699.

Predictors and moderators of treatment outcome for an early psychosis intervention

20 Kraemer HC, Wilson GT, Fairburn CG, Agras WS. Mediators and moderators 35 Foerster A, Lewis S, Owen M, Murray R. Pre-morbid adjustment and
of treatment effects in randomized clinical trials. Arch Gen Psychiatry 2002; personality in psychosis. Effects of sex and diagnosis. Br J Psychiatry
59: 87783. 1991; 158: 1716.
21 Jeppesen P, Petersen L, Thorup A, Abel MB, Ohlenschlaeger J, 36 David A, Buchanan A, Reed A, Almeida O. The assessment of insight in
Christensen TO, et al. The association between pre-morbid adjustment, psychosis. Br J Psychiatry 1992; 161: 599602
duration of untreated psychosis and outcome in first-episode psychosis. 37 Singh SP, Cooper JE, Fisher HL, Tarrant CJ, Lloyd T, Banjo J, et al. Determining
Psychol Med 2008; 38: 15766. the chronology and components of psychosis onset: the Nottingham Onset
22 Marshall M, Lewis S, Lockwood A, Drake R, Jones P, Croudace T. Schedule (NOS). Schizophr Res 2005; 80: 11730.
Association between duration of untreated psychosis and outcome in 38 Campbell MK, Piaggio G, Elbourne DR, Altman DG; CONSORT Group. Consort
cohorts of first-episode patients: a systematic review. Arch Gen Psychiatry 2010 statement: extension to cluster randomised trials. BMJ 2012; 345:
2005; 62: 97583. e5661.
23 Malla A, Norman R, Schmitz N, Manchanda R, Bechard-Evans L, Takhar J, 39 Kraemer HC. Discovering, comparing, and combining moderators of
et al. Predictors of rate and time to remission in first-episode psychosis: treatment on outcome after randomized clinical trials: a parametric
a two-year outcome study. Psychol Med 2006; 36: 6498. approach. Stat Med 2013; 32: 196473.
24 Ayesa-Arriola R, Rodrguez-Sanchez JM, Perez-Iglesias R, Gonzalez-Blanch C, 40 Salimi K, Jarskog LF, Lieberman JA. Antipsychotic drugs for first-episode
Pardo-Garca G, Tabares-Seisdedos R, et al. The relevance of cognitive, schizophrenia: a comparative review. CNS Drugs 2009; 23: 83755.
clinical and premorbid variables in predicting functional outcome for
41 Schennach R, Riedel M, Musil R, Moller HJ. Treatment response in first-
individuals with first-episode psychosis: a 3 year longitudinal study.
episode schizophrenia. Clin Psychopharmacol Neurosci 2012; 10: 7887.
Psychiatry Res 2013; 209: 3028.
42 Howard R, Rabins PV, Seeman MV, Jeste DV. Late-onset schizophrenia and
25 World Health Organization. The ICD-10 Classification of Mental and very-late-onset schizophrenia-like psychosis: an international consensus.
Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. The International Late-Onset Schizophrenia Group. Am J Psychiatry 2000;
WHO, 1992. 157: 1728.
26 World Health Organization. Schedules for Clinical Assessment in 43 Vahia IV, Palmer BW, Depp C, Fellows I, Golshan S, Kraemer G, et al.
Neuropsychiatry (SCAN), Version 1.0. WHO, 1992. Is late-onset schizophrenia a subtype of schizophrenia? Acta Psychiatr
27 Kuipers E, Fowler D, Garety P, Chisholm D, Freeman D, Dunn G, et al. Scand 2010; 122: 41426.
LondonEast Anglia randomised controlled trial of cognitivebehavioural 44 Smeets-Janssen MM, Meesters PD, Comijs HC, Eikelenboom P, Smit JH,
therapy for psychosis. III: follow-up and economic evaluation at 18 months. de Haan L, et al. Theory of Mind differences in older patients with early-onset
Br J Psychiatry 1998; 173: 6168. and late-onset paranoid schizophrenia. Int J Geriatr Psychiatry 2013; 28:
28 Garety PA, Fowler DG, Freeman D, Bebbington P, Dunn G, Kuipers E. 11416.
Cognitivebehavioural therapy and family intervention for relapse 45 Hanssen M, van der Werf M, Verkaaik M, Arts B, Myin-Germeys I, van Os J,
prevention and symptom reduction in psychosis: randomised controlled et al. Comparative study of clinical and neuropsychological characteristics
trial. Br J Psychiatry 2008; 192: 41223. between early, late and very-late-onset schizophrenia-spectrum disorders.
29 Kuipers E, Leff J, Lam D. Family Work for Schizophrenia: A Practical Guide. Am J Geriatr Psychiatry 2015; 23: 85262.
Gaskell, 2002. 46 Selvendra A, Baetens D, Trauer T, Petrakis M, Castle D. First episode
30 Burns T, Firn M. Assertive Outreach in Mental Health. A Manual for psychosis in an adult area mental health service a closer look at early and
Practitioners. Oxford University Press, 2002. late-onset first episode psychosis. Australas Psychiatry 2014; 22: 23541.
47 Greenfield P, Joshi S, Christian S, Lekkos P, Gregorowicz A, Fisher HL,
31 Ferrannini L, Ghio L, Gibertoni D, Lora A, Tibaldi G, Neri G, et al. Thirty-five
et al. First episode psychosis in the over 35s: is there a role for early
years of community psychiatry in Italy. J Nerv Ment Dis 2014; 202: 4329.
intervention? Early Interv Psychiatry 2016; Mar 28 (epub ahead of print).
32 Kay SR, Fiszbein A Opler LA. The Positive and Negative Syndrome Scale for
48 Lappin JM, Heslin M, Jones PB, Doody GA, Reininghaus UA, Demjaha A, et al.
schizophrenia. Schizophr Bull 1987; 13: 26176.
Outcomes following first-episode psychosis - why we should intervene early
33 American Psychiatric Association. Diagnostic and Statistical Manual of in all ages, not only in youth. Aust NZ J Psychiatry 2016; 50: 105563.
Mental Disorder (4th edn) (DSM-IV). APA, 1994.
49 Boutron I, Tubach F, Giraudeau B, Ravaud P. Blinding was judged more
34 Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry difficult to achieve and maintain in nonpharmacologic than pharmacologic
1960, 23: 5662. trials. J Clin Epidemiol 2004; 57: 54350.

Data supplement to Lasalvia et al. Predictors and moderators of treatment outcome in
patients receiving multi-element psychosocial intervention for early psychosis: results
from the GET UP pragmatic cluster randomised controlled trial. Br J Psychiatry doi:

2 The GET UP Group

8 Table DS1 Potential predictors/moderators of treatment outcome

THE GET UP GROUP includes:

GET UP - Genetics, Endophenotypes, Treatment: Understanding early Psychosis

NationalCoordinator:Professor Mirella Ruggeri (Verona)

Leading Project: PPIIAANNO

O (Psychosis: Early Intervention and Assessment of Needs and Outcome)
Scientific Coordinator: Mirella Ruggeri (Verona)
Administrative Leading Institution: Azienda Ospedaliera Universitaria Integrata Verona, Regione
Coordinating Centre: Mario Ballarin, Maria Elena Bertani, Sarah Bissoli, Chiara Bonetto, Doriana
Cristofalo, Katia De Santi, Antonio Lasalvia, Silvia Lunardi, Valentina Negretto, Sara Poli, Sarah
Tosato, Maria Grazia Zamboni

Project TRUMPET (TRaining and Understanding of Service Models for Psychosis Early Treatment)
Scientific Coordinator: Giovanni De Girolamo (Bologna and Brescia)
Administrative Leading Institution: Agenzia Sanitaria e Sociale Regionale, Regione Emilia
Coordinating Centre: Angelo Fioritti, Giovanni Neri, Francesca Pileggi, Paola Rucci

Project GUITAR (Genetic data Utilization and Implementation of Targeted Drug Administration
_in the Clinical Routine)
Scientific Coordinator: Massimo Gennarelli (Brescia)
Administrative Leading Institution: IRCCS Centro S.Giovanni di Dio Fatebenefratelli, Brescia
Coordinating Centre: Luisella Bocchio Chiavetto, Catia Scasselatti, Roberta Zanardini

COgnitive Neuroendophenotypes for Treatment and RehAbilitation of psychoses: Brain imaging,
InflAmmation and StreSS
Scientific Coordinator: Paolo Brambilla (Udine and Verona)
Administrative Leading Institution: Azienda Ospedaliera Universitaria Integrata, Verona, Regione
Coordinating Centre: Marcella Bellani, Alessandra Bertoldo, Veronica Marinelli, Cinzia Perlini,
Gianluca Rambaldelli

RESEARCH UNIT Western Veneto:
Coordinator: Antonio Lasalvia (Verona).
Administrative Leading Institution: Azienda Ospedaliera Universitaria Integrata, Verona.
Coordinating Centre: Mariaelena Bertani, Sarah Bissoli, Lorenza Lazzarotto.
Participating MHCs: TAU Arm: Ulss 3 (Bassano), Ulss 4 Alto Vicentino (Thiene), Ulss 5 Montecchio
(Centro; Sud), Ulss 6 Vicenza ( Secondo), Ulss 18 Rovigo (Rovigo), Ulss 20 Verona ( II Servizio), Ulss 22
Bussolengo (Isola della Scala).
Experimental Arm: Ulss 5 Montecchio (Nord), Ulss 6 Vicenza (Primo; Noventa), Ulss 18 Rovigo ( Badia),
Ulss 19 Adria (Adria), Ulss 20 Verona (I Servizio; III Servizio; La Filanda),Ulss 21 Legnago (Il Tulipano; il
MHCs Reference Persons: Sonia Bardella, Francesco Gardellin, Dario Lamonaca, Antonio Lasalvia, Marco
Lunardon, Renato Magnabosco, Marilena Martucci, Stylianos Nicolau Francesco Nifosi, Michele
Pavanati, Massimo Rossi, Carlo Piazza, Gabriella Piccione, Annalisa Sala, Benedetta Stefani, Spyridon
CBT Staff: Mirko Balbo, Ileana Boggian, Enrico Ceccato, Rosa DallAgnola, Francesco Gardellin, Barbara
Girotto, Claudia Goss, Dario Lamonaca, Antonio Lasalvia, Alessia Mai, Annalisa Pasqualini, Michele
Pavanati, Carlo Piazza, Gabriella Piccione, Stefano Roccato, Alberto Rossi, Spyridon Zotos.
Family Intervention Staff: Flavia Aldi, Barbara Bianchi, Paola Cappellari, Raffaello Conti, Laura De Battisti,
Silvia Merlin,. Tecla Pozzan, Lucio Sarto.
Case Management Staff: Andrea Brazzoli, Antonella Campi, Roberta Carmagnani, Sabrina Giambelli,
Annalisa Gianella, Lino Lunardi, Davide Madaghiele, Paola Maestrelli, Lidia Paiola, Elisa Posteri, Loretta
Viola, Valentina Zamberlan, Marta Zenari.
Biological Sample processing and support to Brain Imaging precedures: Sarah Tosato, Martina Zanoni,
Giovanni Bonadonna, Mariacristina Bonomo.

RESEARCH UNIT Eastern Veneto:

Coordinator: Paolo Santonastaso.
Administrative Leading Institution: University of Padua.
Coordinating Centre: Carla Cremonese, Paolo Scocco, Angela Veronese.
Participating MHCs: TAU Arm: Ulss 8 ( Castelfranco), Ulss 9 (Treviso Nord; Oderzo), Ulss 10 (San Don di
Piave), Ulss 12 (Venezia; Mestre sud), Ulss 13 (Dolo), Ulss 14 (Piove di Sacco), Ulss 15 ( Cittadella), Ulss
16 (II Servizio), Ulss 17 (Este; Montagnana).
Experimental Arm: Ulss 8 (Montebelluna; Valdobbiadene), Ulss 9 (Treviso; Mogliano Veneto), Ulss 10
(PortogReserach Unitaro), Ulss 12 (Mestre Centro), Ulss 13 (Mirano), Ulss 14 (Chioggia I; Cavarzere),
Ulss 15 (Camposanpiero), Ulss 16 (I Srvizio; III Servizio), Ulss 17 (Monselice; Conselve).
MHCs Reference Persons: Patrizia Anderle, Andrea Angelozzi, Isabelle Amalric Gabriella Baron,, Enrico
Bruttomesso Fabio Candeago, Franco Castelli, Maria Chieco, Carla Cremonese, Enrico Di Costanzo,
Mario Derossi, Michele Doriguzzi, Osvaldo Galvano, Marcello Lattanzi, Roberto Lezzi, Marisa Marcato,
Alessandro Marcolin, Franco Marini, Stefano Marino, Manlio Matranga, Elisabetta Sabbadin, , Rossana
Riolo, Maria Zucchetto, Flavio Zadro.
CBT Staff: Daniela Argenti, Giovanni Austoni, Maria Bianco, Stefania Bordino, Linda Cibiniel, Maria Chieco,
Marco DallAsta, Filippo Dario, Francesca Dassi, Alessandro Di Risio, Aldo Gatto, Simona Gran,
Emanuele Favero, Anna Franceschini, Silvia Friederici, Vanna Marangon, Marisa Marcato, Stefano
Marino, Giorgio Martinelli, Michela Pascolo, Maya Piaia, Luana Ramon, Elisabetta Sabbadin, Paolo
Scocco, Mara Semenzin, Angela Veronese, Stefania Zambolin, Maria Zucchetto. Anna Dominoni.
Family Intervention Staff: Antonella Buffon, Carla Cremonese, Elena Di Bortolo, Silvia Friederici, Stefania
Fortin,Marisa Marcato, Francesco Matarrese, Simona Mogni, Novella Nicodemo, Alessio Russo,
Alessandra Silvestro, Elena Turella, Paola Viel.

Case Management Staff: Lorenzo Andreose, Mario Boenco, Daniela Bottega, Loretta Bressan, Arianno
Cabbia, Elisabetta Canesso, Romina Cian, Caludia Dal Piccol, Maria Dalla Pasqua, Cinzia De Gasperi,
Anna Di Prisco, Lorena Mantellato, Monica Luison, Sandra Morgante, Mirna Santi, Moreno Sacillotto,
Mauro Scabbio, Patrizia Sponga, MLuisa Sguotto, Flavia Stach, MGrazia Vettorato.
Biological Sample processing and support to Brain Imaging precedures: Oscar Cabianca, Amalia Valente,
Livio Caberlotto, Alberto Passoni, Patrizia Flumian, Luigino Daniel, Massimo Gion, Saverio Stanziale,
Flora Alborino, Vladimiro Bortolozzo, Lucio Bacelle, Leonarda Bicciato, Daniela Basso, Filippo Navaglia,
Fabio Manoni, Mauro Ercolin.


Coordinators: Giovanni Neri, Franco Giubilini.
Administrative Leading Institution: Azienda ULSS, Parma
Coordinating Centre: Massimiliano Imbesi, Emanuela Leuci, Fausto Mazzi, Enrico Semrov.
Participating MHCs: TAU Arm: Piacenza (Castel S.Giovanni), Parma (Parma Est; Sud Est; Valli Taro e
Ceno), Reggio Emilia (CastelNovo nei Monti; Montecchio), Modena (Mirandola; Polo Ovest; Sassuolo;
Experimental Arm: Piacenza (Piacenza; Fiorenzuola), Parma (Nord; Ovest; Fidenza), Reggio Emilia
(Correggio; Guastalla; Reggio Emilia III; Reggio Emilia; Scandiano), Modena ( Carpi; Polo Est; Vignola).
MHCs Reference Persons: Silvio Anelli, Mario Amore, Laura Bigi, Welsch Britta, Giovanna Barazzoni Anna,
Rubes Bonatti, Maria Borziani, Stefano Crosato, Isabella Fabris, Raffaele Galluccio, Margherita Galeotti,
Mauro Gozzi, Vanna Greco, Emanuele Guagnini, Stefania Pagani, Silvio Maccherozzi, Raffaello Malvasi,
Francesco Marchi, Ermanno Melato, Elena Mazzucchi, Franco Marzullo, Pietro Pellegrini, Nicoletta
Petrolini, Donatella Silvia Rizzi, Paolo Volta.
CBT Staff: Silvio Anelli, Franca Bonara, Elisabetta Brusamonti, Roberto Croci, Ivana Flamia, Francesca
Fontana, Romina Losi, Fausto Mazzi, Roberto Marchioro, Stefania Pagani, Luigi Raffaini, Luca Ruju,
Antonio Saginario, Giulia Stabili, Grazia Tondelli.
Family Intervention Staff: Lucia Bernardelli, Federica Bonacini, Annaluisa Florindo, Marina Merli, Patrizia
Nappo, Lorena Sola, Ornella Tondelli, Matteo Tonna, MTeresa Torre, Morena Tosatti, Gloria Venturelli,
Daria Zampolli.
Case Management Staff: Antonia Bernardi, Cinzia Cavalli, Lorena Cigala, Cinzia Ciraudo, Antonia Di Bari,
Lorena Ferri, Fabiana Gombi, Sonia Leurini, Elena Mandatelli, Stefano Maccaferri, Mara Oroboncoide,
Barbara Pisa, Cristina Ricci.
Biological Sample processing and support to Brain Imaging precedures: Enrica Poggi, Mara
Oroboncoide, Corrado Zurlini, Monica Malpeli, Rossana Colla, Elvira Teodori, Luigi Vecchia, Rocco
D'Andrea, Tommaso Trenti , Paola Paolini


Coordinators: Francesca Pileggi, Daniela Ghigi.
Administrative Leading Institution: Azienda ULSS, Rimini
Coordinating Centre: Mariateresa Gagliostro , Michela Pratelli, Paola Rucci
Participating MHCs: TAU Arm: Bologna (Zanolini; Scalo; Casalecchio; Vergato; San Giovanni), Ferrara (CSA
Ferrara; SIPI Ferrara Sud; Codigoro; Portomaggiore), Ravenna (Ravenna; Fenza), Forl (Forl), Cesena
(Cesena), Rimini (Riccione).
Experimental Arm: Bologna (Mazzacorati; Tiarini, Nani; S. Lazzaro; Budrio; San Giorgio), Imola
(UOT_Imola), Ferarra (Copparo; Ferrara Nord; Cento), Ravenna (Lugo), Cesena (Rubicone), Rimini
MHCs Reference Persons: Antonio Antonelli, Luana Battistini, Francesca Bellini, Eva Bonini, Caterina
Bruschi Rossella Capelli, Cinzia Di Domizio, Chiara Drei, Giuseppe Fucci, Alessandra Gualandi, Maria
Rosaria Grazia, Anna M. Losi, Franca Mazzanti Paola Mazzoni, Daniela Marangoni, Giuseppe Monna,

Marco Morselli, Alessandro Oggioni, Silvio Oprandi, Walter Paganelli, Morena Passerini, Maria Piscitelli,
Gregorio Reggiani, Gabriella Rossi, Federica Salvatori, Simona Trasforini, , Carlo Uslenghi, Simona
CBT Staff: Giovanna Bartolucci, Rosita Baruffa, Francesca Bellini, Raffaella Bertelli, Lidia Borghi, Patrizia
Ciavarella, Cinzia DiDomizio, Giuseppe Monna, Alessandro Oggioni, Elisabetta Paltrinieri, Maria
Piscitelli, Francesco Rizzardi, Piera Serra, Damiano Suzzi, Uslenghi Carlo.

Family Intervention Staff: Paolo Arienti, Fabio Aureli, Rosita Avanzi, Vincenzo Callegari, Alessandra
Corsino, Paolo Host, Rossella Michetti, Michela Pratelli,Francesco Rizzo, Paola Simoncelli, Elena Soldati,
Eraldo Succi.
Case Management Staff: Massimo Bertozzi, Elisa Canetti,Luca Cavicchioli, Elisa Ceccarelli, Stefano Cenni,
Glenda Marzola, Vanessa Gallina, Carla Leoni, Andrea Olivieri, Elena Piccolo, Sabrina Ravagli, Rosaria
Russo, Daniele Tedeschini.
Biological Sample processing and support to Brain Imaging precedures: Marina Verenini, Walter Abram,
Veronica Granata, Alessandro Curcio, Giovanni Guerra, Samuela Granini, Lara Natali, Enrica Montanari,
Fulvia Pasi, Umbertina Ventura, Stefania Valenti, Masi Francesca, Rossano Farneti, Paolo Ravagli,
Romina Floris, Otello Maroncelli, Gianbattista Volpones, Donatella Casali.


Coordinator: Maurizio Miceli.
Administrative Leading Institution: Azienda Sanitaria di Firenze
Coordinating Centre: Maurizio Miceli.
Participating MHCs: TAU Arm: MOM SMA 5; MOM SMA 8; MOM SMA 11; MOM SMA 12.
Experimental Arm: MOM SMA 3; MOM SMA 7; MOM SMA 9; MOM SMA 10.
MHCs Reference Persons: Andrea Bencini, Massimo Cellini, Luca De Biase, Leonardo Barbara, Liedl
Charles, Maurizio Miceli, Cristina Pratesi, Andrea Tanini, Roberto Leonetti.
CBT Staff: Massimo Cellini, Maurizio Miceli, Riccardo Loparrino, Cristina Pratesi, Cinzia Ulivelli,
Family Intervention Staff: Cristina Cussoto, Nico Dei, Enrico Fumanti, Manuela Pantani, Gregorio Zeloni.
Case Management Staff: Rossella Bellini, Roberta Cellesi, Nadia Dorigo, Patrizia Gull, Luisa Ialeggio,
Maria Pisanu.
Biological Sample processing and support to Brain Imaging precedures: Graziella Rinaldi, Angela Konze

RESEARCH UNIT Milano Niguarda:

Coordinator: Angelo Cocchi.
Administrative Leading Institution: Azienda Ospedaliera Ospedale Niguarda Ca Granda, Milano
Coordinating Centre: Anna Meneghelli
Participating MHCs: TAU Arm: corso Plebisciti; via Mario Bianco.
Experimental Arm: via Cherasco e via Livigno; via Litta Modignani.
MHC Reference Persons: Maria Frova , Emiliano Monzani, Alberto Zanobio, Marina Malagoli, Roberto
CBT Staff: Simona Barbera, Carla Morganti, Emiliano Monzani, Elisabetta Sarzi Amad.
Family Intervention Staff: Virginia Brambilla, Anita Montanari.
Case Management Staff: Giori Caterina, Carmelo Lopez.
Biological Sample processing and support to Brain Imaging precedures: Alessandro Marocchi, Andrea
Moletta, Maurizio Sberna

RESEARCH UNIT Milano S. Paolo:

Coordinator: Silvio Scarone.
Administrative Leading Institution: Azienda ULSS San Paolo, Milano
Coordinating Centre: Maria Laura Manzone
Participating MHCs: TAU Arm: CPS Zona 14 (Barabino).
Experimental Arm: Rozzano; Zona 15 (Conca del Naviglio); Zona 16 (San Vigilio).
MHC Reference Persons: Barbera Barbara, Luisa Mari, Maria L. Manzone, Edoardo Razzini.
CBT Staff: Yvonne Bianchi, MRosa Pellizzer, Antonella Verdecchia.
Family Intervention Staff: MGabriella Sferrazza, MLaura Manzone, Carmine Pismataro.
Case Management Staff: Benedetta Cerrai, Alessandra Gambino, Rosa Panarello.
Biological Sample processing and support to Brain Imaging precedures: Gian Vico Melzi D'Eril,
Alessandra Barassi, Rosana Pacciolla, Gloria Faraci


Coordinator: Stefano Torresani (Bolzano).
Administrative Leading Institution: Azienda Sanitaria,, Bolzano
Participating MHCs: TAU Arm: none
Experimental Arm: Bolzano Rossini; Bolzano del Ronco.
MHC Reference Persons: Fabio Carpi, Soelva Margit.
CBT Staff: Monica Anderlan, Michele De Francesco, Efi Duregger, Stefano Torresani, Carla Vettori.
Family Intervention Staff: Carpi Fabio, Doimo Sabrina, Kompatscher Erika, Soelva Margit, Stefano
Case Management Staff: Forer Michael, Kerschbaumer Helene.
Biological Sample processing and support to Brain Imaging precedures: Anna Gamper, Maira Nicoletti


Chiara Acerbi, Daniele Aquilino, Silvia Azzali, Luca Bensi, Sarah Bissoli, Davide Cappellari, Elisa Casana,
Nadia Campagnola, Elisa Dal Corso, Elisabetta Di Micco, Erika Gobbi, Laura Ferri, Erika Gobbi, Laura
Mairaghi, Sara Malak, Luca Mesiano, Federica Paterlini, Michela Perini, Elena Maria Puliti, Rosaria Rispoli,
Elisabetta Rizzo, Chiara Sergenti, Manuela Soave, Elisabetta Di Micco, Rosaria Rispoli.


Andrea Alpi, Laura Bislenghi, Tiziana Bolis, Francesca Colnaghi, Simona Fascendini, Silvia Grignani, Anna
Meneghelli, Giovanni Patelli.


RESEARCH UNIT Life Events Firenze - Coordinator: Carlo Faravelli
Coordinating Centre: Silvia Casale
Administrative Leading Institution: University of Florence

RESEARCH UNIT Communications Skills - Coordinator: Christa Zimmermann

Coordinating Centre: Giuseppe Deledda, Claudia Goss, Mariangela Mazzi, Michela Rimondini.
Administrative Leading Institution: University of Verona

RESEARCH UNIT Genetics-IRCCS, FBF Brescia Coordinator: Massimo Gennarelli

Coordinating Centre: Catia Scassellati, Cristian Bonvicini, Sara Longo
Administrative Leading Institution: IRCCS Centro S.Giovanni di Dio Fatebenefratelli, Brescia

RESEARCH UNIT Neuropsicopharmacology-IRCCS, FBF Brescia Coordinator: Luisella Bocchio Chiavetto
Coordinating Centre: Roberta Zanardini
Administrative Leading Institution: IRCCS Centro S.Giovanni di Dio Fatebenefratelli, Brescia

RESEARCH UNIT Molecular Biology, AFaR, FBF, Roma Coordinator: Mariacarla Ventriglia
Coordinating Centre: Rosanna Squitti
Administrative Leading Institution: Department of Neuroscience, AFaR-Fatebenefratelli Hospital, Rome,

RESEARCH UNIT LENITEM - IRCCS, FBF Brescia Coordinator: Giovanni Frisoni

Coordinating Centre: Michela Pievani
Administrative Leading Institution: IRCCS Centro S.Giovanni di Dio Fatebenefratelli, Brescia

RESEARCH UNIT RUBIN, Udine-Verona Coordinator: Matteo Balestrieri

Coordinating Centre: Paolo Brambilla, Cinzia Perlini, Veronica Marinelli, Marcella Bellani, Gianluca
Rambaldelli, Alessandra Bertoldo, Paolo Carpeggiani, Alberto Beltramello, Franco Alessandrini,
Francesca Pizzini, Giada Zoccatelli, Maurizio Sberna, Angela Konze
Administrative Leading Institution: DISM, Universit di Udine, Udine (Mrs Marina Dorligh)

RESEARCH UNIT STRESS, University of Pavia Coordinator: Pierluigi Politi

Coordinating Centre: Enzo Emanuele, Natascia Brondino.

RESEARCH UNIT Neuroimmunologiy-IRCCS S. Raffaele, Milano Coordinator: Gianvito Martino

Coordinating Centre: Alessandra Bergami e Roberto Zarbo

RESEARCH UNIT Animal Models, Univ. Milano Coordinator: Marco Andrea Riva

Coordinating Centre: Fabio Fumagalli, Raffaella Molteni, Francesca Calabrese, Gianluigi Guidotti,
AlessiaLuoni, Flavia Macchi.


Stefania Artioli, Marco Baldetti, Milena Bizzocchi, Donatella Bolzon, Elisa Bonello, Giorgia Cacciari, Claudia
Carraresi, MTeresa Cascio, Gabriele Caselli, Karin Furlato, Sara Garlassi, Alessandro Gavarini, Silvia
Lunardi, Fabio Macchetti, Valentina Marteddu, Giorgia Plebiscita, Sara Poli, Stefano Totaro.


Tali Corona Mattioli


PIANO: Paul Bebbington, Max Birchwood, Paola Dazzan, Elisabeth Kuipers, Graham Thornicroft;
GUITAR: Carmine Pariante; CONTRABASS: Steve Lawrie, Carmine Pariante, Jair C. Soares

Table DS1 Potential predictors/moderators of treatment outcome (experimental treatment group,
n=272; TAU group, n=172).

BASELINE (after clinical

Treatment as Experimental P-value
usual group treatment (Chi-square or
(n=172) group t-test, where
(n=272) appropriate)
Age at first contact with services, mean
(s.d.) 31.5 (9.2) 29.3 (9.8) 0.017
<35 years, n (%) 106 (61.6%) 194 (71.3%) 0.033
35 years, n (%) 66 (38.4%) 78 (28.7%)
Gender, n (%)
Male 94 (54.7%) 166 (61.0%) 0.184
Female 78 (45.3%) 106 (39.0%)
Citizenship, n (%)
Italy 149 (86.6%) 241 (88.6%) 0.535
Other 23 (13.4%) 31 (11.4%)
Education, n (%) (13 missing) (9 missing)
Low (primary-middle school) 68 (42.8%) 95 (36.1%) 0.174
High (secondary school, university) 91 (57.2%) 168 (63.9%)
Duration of Untreated Psychosis DUP (30 missing) (31 missing)
(months), mean (s.d.) 7.7 (18.3) 7.4 (17.6) 0.870
Insight SAI, mean (s.d.) (60 missing) (55 missing)
Attribution of Symptoms 5.72 (3.30) 5.41 (3.27) 0.457
Illness Awareness 8.12 (1.64) 7.67 (1.71) 0.121
Treatment Adherence 4.24 (1.73) 3.78 (1.89) 0.032
Type of Psychosis, n (%)
Non-affective psychosis 132 (76.7%) 214 (78.7%) 0.632
Affective psychosis 40 (23.3%) 58 (21.3%)
Premorbid Social Adjustment PAS, mean (70 missing) (62 missing)
Social Childhood 1.50 (1.22) 1.62 (1.30) 0.433
School Childhood 1.35 (1.00) 1.31 (1.11) 0.752
Social Adolescence 2.00 (1.43) 2.05 (1.44) 0.785
School Adolescence 1.98 (1.77) 1.83 (1.36) 0.389

Predictors and moderators of treatment outcome in patients
receiving multi-element psychosocial intervention for early
psychosis: results from the GET UP pragmatic cluster
randomised controlled trial
Antonio Lasalvia, Chiara Bonetto, Jacopo Lenzi, Paola Rucci, Laura Iozzino, Massimo Cellini, Carla
Comacchio, Doriana Cristofalo, Armando D'Agostino, Giovanni de Girolamo, Katia De Santi, Daniela
Ghigi, Emanuela Leuci, Maurizio Miceli, Anna Meneghelli, Francesca Pileggi, Silvio Scarone, Paolo
Santonastaso, Stefano Torresani, Sarah Tosato, Angela Veronese, Angelo Fioritti, Mirella Ruggeri and
the GET UP Group
BJP 2017, 210:342-349.
Access the most recent version at DOI: 10.1192/bjp.bp.116.190058

Supplementary Supplementary material can be found at:


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