combined individual and family therapy in comparison to
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1 2 3 Combined individual and family therapy in comparison to 4 5 treatment as usual for people at-risk of psychosis: A feasibility 6
7 study (IF CBT): Trial rationale, methodology and baseline characteristics 8 9 10 11
12 Authors:
13 Heather Law1, 2 , Emma Izon1, 2, Karmen Au-Yeung1, Anthony P. Morrison1, 2,
15 Rory Byrne1, 2, Caitlin Notley3, Alison Yung2 , John Norrie4, and Paul French5,61,
16 17 18
19 1 Greater Manchester Mental Health NHS Foundation Trust,
20 Research and Development
22 2University of Manchester 23 24 3University of East Anglia, Norwich Medical School 25
26 4 University of Edinburgh, Centre for Population Health Sciences
27 5 Manchester Metropolitan University
29 6 Pennine Care NHS Foundation Trust
30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 3 ABSTRACT 4 5 6
7 Background:
8 Current National Institute for Health and Care Excellence (NICE) guidelines for psychosis
10 recommend psychological therapy with or without family 11 12 intervention for individuals at-risk of developing psychosis.
13 NICE guidelines have a
15 specific research recommendation to investigate the clinical and cost effectiveness of
16 17 combined individual and family intervention. We report the rationale, design and 18
19 baseline characteristics of a feasibility study investigating combined Individual
20 and Family Cognitive Behavioural Therapy (IFCBT).
22 23 24 25
26 Methods:
27 The IFCBT study was a single blind, pilot randomised controlled trial (RCT) to compare a
29 combined individual and family Cognitive Behavioural Therapy (CBT) intervention to 30 31 treatment as usual. Participants were assessed using the Comprehensive Assessment of the
32 At-risk Mental State (CAARMS) and randomly allocated to either therapy or enhanced
34 treatment as usual (ETAU). All participants were followed up at six and twelve months. 35 36 Primary feasibility outcomes were recruitment and retention of participants. Secondary 37
38 outcomes included transition to psychosis and assessment of mood, anxiety and the
39 relationship of the individual and nominated family member.
41 42 43 44
45 Results:
46 We report data showing entry into the study from initial enquiry to randomisation. We report
48 the characteristics of the recruited sample of individuals (n=70) and family members (n=70) 49
50 at baseline 51 52 53 Conclusions: 54 55 The study recruited to 92% of target demonstrating it is feasible to identify and recruit 56
57 participants. Our study aimed to add to the current evidence base regarding the utility of
58 family interventions for people at-risk of psychosis.
60
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1 2 3 Trial registration: 4 5 ISRCTN42478021 6 7 8
This article presents independent research funded by the National Institute for Health
10 Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference 11 12 PB-PG-1014-35075). The views expressed are those of the author(s) and not necessarily
13 those of the NIHR or the Department of Health and Social Care.
15 16 17 Data Sharing 18
19 The data that support the findings of this study are available from the corresponding author
20 upon reasonable request.
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1 2 3 4 5
6 INTRODUCTION 7 8 9 10 Over the last decade there has been increasing interest in the ability to identify and 11
12 intervene early in the onset of psychosis (Fusar-Poli et al., 2013). Researchers have
13 validated operational criteria to identify those with an ‘At-risk Mental State’
15 (ARMS) for psychosis, allowing early identification of individuals at high risk of 16 17 developing Schizophrenia or related psychotic disorders. Following successful 18
19 identification of people meeting criteria for ARMS, researchers and clinicians are now
20 focusing on prevention and intervention strategies. The personal, social and economic
22 burden associated with psychosis has been a key driver for development of effective 23 24 interventions to prevent transition to psychosis. 25 26
Previous studies of transition rates and interventions for people at-risk of
28 psychosis 29 30
31 A systematic review which examined 28 studies, indicated transition rates of
32 children and adolescents from ARMS to psychosis were 40% at 6 months, between 17-
34 20% at 1 year, and between 7-21% at 2 years (Tor et al., 2017). These rates are 35 36 consistent with an earlier meta-analysis of transition outcomes, which found individuals 37
38 to be at very high risk of developing psychosis within the first 3 years of clinical
39 presentation (Fusar-Poli et al., 2012). In the long-term, the ARMS is significantly 40 41 associated with increased risk of developing psychosis, but the accuracy is modest, 42 43 demonstrating the Brief Limited Intermittent Psychotic Symptoms (BLIPS) subgroup at
44 a higher risk compared to the Attenuated Psychotic Symptom (APS) subgroup
46 (p<0.001) (Fusar-Poli et al., 2017). 47 48
49 Several randomised controlled trials (RCTs) of interventions for individuals who meet
50 criteria for ARMS have been conducted. Interventions included non-pharmacological
52 interventions such as CBT (Morrison et al., 2004; Morrison et al., 2012; Stain et al., 53 54 2016; Addington et al., 2011), family therapy (Miklowitz et al., 2014) and cognitive 55
56 remediation (Hooker et al., 2014; Urben et al., 2012); pharmacological interventions
57 using antipsychotics (Bechdolf et al., 2017; McGorry et al., 2013; McGlashan et al.,
59 60
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1 2 3 2006; Woods et al., 2003) and experimental pharmacotherapies such as omega-3 fatty 4 5 acids (Amminger et al., 2010). 6 7 8 9 10 The National Institute for Health and Care Excellence (NICE, 2014) guidelines 11
12 (guideline CG178) development group, found moderate evidence for CBT, concluding
13 that further research in complex psychological interventions is required. This was
15 consistent with findings published in NICE guidelines (2014) for psychosis and 16 17 schizophrenia that suggests antipsychotic medication should not be used as a first line 18
19 treatment of ARMS but supported the use of psychological interventions. They also
20 made a specific research recommendation for the conduct of a trial of combined
22 individual and family therapy for this group. 23 24 25 26 27 A further meta-analysis supported the findings of the NICE guideline group (van der 28 29 Gaag et al., 2013). A 2014 meta-analysis focusing specifically on CBT found that the 30
31 relative risk of developing psychosis was reduced by more than 50% for those receiving
32 CBT at every time point and concluded that CBT-informed treatment is associated with a
34 reduced risk of transition to psychosis at 6, 12 and 18–24 months, and reduced symptoms 35 36 at 12 months (Hutton & Taylor, 2014). 37 38 39 40 41 Results from previous treatment studies have been invariably mixed and often 42
43 conflicting. The evidence for a specific intervention superiority in psychosis prevention
44 remains inconclusive (Davies et al., 2018). However earlier meta-analysis that compare
46 all trial interventions (both psychosocial and pharmacological) with needs-based 47 48 interventions indicate that in group-level analysis of most ARMS individuals improve in 49
50 their symptoms and functioning over time, with transition rated reduced and delayed
51 (Nelson, Amminger & McGorry, 2018).
53 54 55 56 57 58 59 60
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Study rationale and aims
To our knowledge, there have been two published studies
examining the potential for family interventions with this group to reduce the rate of
transition to psychosis. This is despite the evidence base for family interventions for
psychosis, which show an ability to reduce relapse rates and provide better prognosis
(Pharoah, Mari, Rathbone, & Wong, 2010; Pitschel-Walz,
49 Leucht, Bäuml, Kissling, & Engel, 2001). In addition, a recent systematic review looking
50 at the family environment in ARMS found higher criticism and hostility linked to poorer
functioning and worse symptoms in families of ARMS, with similar rates of high
expressed emotion compared to First Episode Psychosis (Izon et al., 2018). Miklowitz et
56 al. (2014) found 6 of 102 participants transitioned to psychosis, with an overall risk of
57 6%. None of the 6 participants who converted were taking antipsychotic medications at
58 entry. There were fewer transitions in the FI group (2% compared to 11%) with the FI
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1 2 3 participant transitioning within 30 days of randomisation. The FI was associated with 4 5 greater improvements in attenuated symptoms over 6 months relative to control. Key 6
7 components included psychoeducation and development of a prevention plan with the
8 service-user and family. Sessions focused on improving communication and focusing on
10 enhancing problem solving skills. A further study (Landa et al, 2016) investigated 11 12 different group-and-family based CBT interventions, finding statistically significant
13 decreases in attenuated psychotic symptoms, negative symptoms, depression and
15 improvements in functioning. Family members showed significant improvements in use
16 17 of CBT skills, enhanced communication with their offspring, and greater confidence in 18
19 their ability to help. However, this was a small (N=6), open, uncontrolled study and
20 methodological shortcomings from the poor design limit its interpretation.
22 23 24 25
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29 30 31
32
34 35 36
37 Additional family studies found integrated treatment of social skills training and multi-
38 family group psychoeducation significantly reduced risk of transition compared to
40 standard care in ARMS individuals with schizotypal disorder (Nordentoft et al, 2006). 41 42 One pilot study separated individuals at the highest risk of psychosis transition to a 43
44 family-aided assertive community treatment, whilst those with lower risk were assigned
45 to community care (McFarlane et al, 2015). Although there were no differences in
47 transition, the family treatment had some benefits over community care. There is limited 48 49 literature of family RCTs with suggestions for treatment strategies combining family and 50
51 individual CBT (Stafford et al., 2013; Miklowitz et al., 2014; NICE, 2014).
52 53 The current study aimed to investigate the feasibility of a combined Individual and 54 55 Family Cognitive Behavioural Therapy (IFCBT) for people considered to be at- 56
57 risk of developing psychosis. Our primary outcome was to recruit and consent to
58 participate in a randomised trial, adhere to the intervention, retain participants across
60 both arms through assessment at follow-ups and gather data to inform outcome
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1 2 3 parameter estimates. From this, we will be able to assess the acceptability of the 4 5 intervention to service users and their key family member/carer. Furthermore, the trial 6
7 will provide initial indications of the impact of a combined approach of individual CBT
8 and family intervention on transition rates to inform the primary outcomes for a future
10 definitive randomised controlled Trial (RCT). 11 12
13 METHODS
14 The main study was a single (rater) blind randomised feasibility study with two
16 conditions; Individual and Family CBT (IFCBT) plus enhanced treatment as usual 17 18 (ETAU) vs. ETAU alone in people considered to be at high- risk of developing 19 psychosis. The trial randomly allocated participants who met criteria to a 6-month 21
package of either condition, using a secure telephone randomisation service. 22 23 Assessments were conducted by research assistants, who were blind and independent to 24
25 treatment group. Participants were made aware to conceal their allocation from the
26 research assistants when they were in correspondence and during follow-up assessment.
28 All allocation data was inaccessible to research assistants, with separate offices utilised 29 30 to retain the blind. Assessments were conducted at baseline, post treatment (6 months) 31
32 and follow-up (12 months) with both the individual and their nominated family
33 member/carer. There was also a nested qualitative study to identify key themes
35 associated with the acceptability of IFCBT in individuals at high risk of psychosis and 36 37 experiences of being involved in the trial. Additionally, family members/carers of
38 participants were interviewed to explore their unique experiences to inform these
40 outcomes. 41 42
43 The study was approved by the North West - Greater Manchester East Ethics Committee
44 (REC reference: 16/NW/0278).
46 47 48 49 50 51 52 Participants 53 54 A sample size of 60 is considered adequate for obtaining reliable sample size 55
56 estimates, which will facilitate the main aims of a feasibility study (Sim & Lewis,
57 2012). Based on requiring 60 participants across conditions, a target recruitment of 76
59 (38 per condition) over the recruitment period would allow a dropout rate of 20%. 60
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1 2 3 Formal sample size calculations were not appropriate for a pilot study aimed at 4 5 establishing feasibility and statistical significance of any findings will not be the primary 6
7 focus of the analysis. The sample will also include a family member, carer or loved one
8 as nominated by each participant (we will use the term family/carer for this throughout
10 this paper). 11 12
13 Recruitment took place across 2 mental health trusts in North West England (Greater
14 Manchester Mental Health NHS foundation Trust and Pennine Care NHS Trust)
16 primarily via Early Intervention in Psychosis teams. Participants were also able to self- 17 18 refer via posters or leaflets. Participants were required to meet the following criteria: 19 20
Inclusion Criteria
22 a) Aged 16-35. 23 24 b) Screen positive on the CAARMS for an At-risk Mental State. 25
26 c) Be living (or in regular contact) with a family member, carer or loved one.
27 d) Help seeking. 28 29
30 Exclusion Criteria 31
32 a) Receipt of anantipsychotic medication to
33 treat symptoms of psychosis. 34 35 b) Moderate to severe learning disability. 36
37 c) Organic impairment. 38 d) Insufficient fluency in English.
40 e) Significant risk to self or others. 41 42 43
44 Assessment of eligibility and outcome measures
45 Trial eligibility was assessed using the Comprehensive Assessment of At-risk
47 Mental States (CAARMS) with participants meeting criteria for one of the three ARMS 48 49 subgroups 50 51
i) trait vulnerability risk factors, defined by the presence of either a first degree
53 relative with a history of psychosis or a pre-existing schizotypal personality 54 55 disorder; 56 57
ii) state risk factors, defined by the presence of transient psychotic symptoms,
59 called Brief Limited Intermittent Psychotic Symptoms (BLIPS); 60
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1 2 3 iii) state risk factors, defined by Attenuated Psychotic Symptoms 4 5 (APS). 6 7
According to the CAARMS criteria (Yung et al., 2006), individuals within each
9 subgroup also need to display reduced or chronic low functioning and need to be help 10 11 seeking. 12 13
Full assessments were conducted by assessors blind and independent to treatment group
15 on three occasions: initial baseline, 6 months post randomisation (post-treatment for the 16 17 therapy group) and 12 months post randomisation. Individual participants were 18
19 reimbursed £20 for their time at each assessment, family member/carers £10 and both
20 received £10 for any additional qualitative interviews. All eligibility decisions were
22 confirmed by a qualified clinician and all assessors were fully trained in the measures 23 24 used. Table 1 summarises the measures used at each assessment time point. 25 26 27 28 29 [Insert Table 1 Assessment schedule] 30 31 32 33 34 The main objective was to evaluate the feasibility of the trial. Primary feasibility 35 36 outcomes were therefore: recruitment and retention of participants in both arms of the
37 study and adherence to therapy. The primary clinical outcome is transition to psychosis
39 as defined by the Comprehensive Assessment of At-risk Mental States 40 41 (CAARMS). 42 43
Secondary outcome measures for both participant and family member/carer will include
45 the Time Use Survey, Beck Depression Inventory (BDI) and the Social Interaction 46 47 Anxiety Scale (SIAS). 48
49
50 Data on health status will be collected by the EQ-5D and used to estimate the
52 health-related utility scores of participants. Furthermore, we assessed 53 54 the relationship and individual’s perceptions of their relationship between themselves 55
56 and the carer using the Family Questionnaire, Five Minute Speech Sample, Relationship
57 Structure Questionnaire (ECR-RS) and the Perceived Criticism and Warmth
59 Questionnaire. Additionally, we assessed carer burden and 60
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1 2 3 additional measures on their carer health (GHQ), and carer needs (BDI, 4 5 SIAS, EPQ) 6
7 8 9 Randomisation 10 11 Following written consent, eligible participants were randomised using Christie's secure 12
13 telephone randomisation service. Randomisation (at the individual level) was
14 independent and concealed, using randomised-permuted blocks of 6-8 and stratified by
16 age and gender. Allocation was communicated to trial manager (to monitor adherence to 17 18 the randomisation algorithm), trial therapist and made known to the participant by letter 19 from the administrator. Blinding of allocation was maintained for research assistants, 21
until all outcome measures for all subjects were collected. Blindness was maintained 22 23 using a range of measures (e.g. separate offices for therapist and researchers, protocols 24
25 for answering phones, message taking and secretarial support, separate diaries and
26 security for electronic randomisation information). A dual-purpose
28 independent Trial Steering Committee (TSC) and Data Monitoring and Ethics 29 30 Committee (DMEC) was set up to oversee the study. 31 32
Interventions
34 The intervention was a combination of Individual and Family Cognitive Behavioural 35 36 Therapy (IFCBT). The individual CBT treatment was based on that used in several 37
38 previous treatment studies (French & Morrison, 2004; Morrison et al., 2012;
39 Morrison et al., 2004). The family component was an additional 4 - 6 sessions of CBT
41 with key family members such as parents or carers, to compliment the individual work. 42 43 Sessions focused on assessment, formulation, problems and goal setting, communication
44 styles and problem solving. The family intervention followed NICE guidelines by
46 including the client and taking account of the relationship between the parent and or 47 48 carer and the young person. The family/carer component was delivered in tandem with 49
50 the individual CBT and delivered by the same therapist to maintain engagement and
51 consistency of approach. Participants received the intervention as well as enhanced
53 treatment as usual (ETAU). 54 55
56 Participants who were not allocated to the intervention arm received
57 (ETAU) alone. Irrespective of their group allocation, all Participants were able
59 to access or continue with their treatment as usual (which may include care from an
60
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1 2 3 Early Intervention Service). Early Intervention Services offer treatment to prevent 4 5 psychosis in accordance with current NICE guidelines which state they should “offer 6
7 individual cognitive behavioural therapy (CBT) with or without family intervention” and
8 “offer interventions recommended in NICE guidance for people with any of the anxiety
10 disorders, depression, emerging personality disorder or substance misuse” (NICE, 2014). 11 12
13 Enhancements to TAU involved monitoring of symptoms via structured interview, which
14 is associated with the perceived benefits including having a chance to talk at length about
16 concerns. Participants were also given a crisis card providing contact details for 17 18 appropriate local sources of help in psychiatric emergency and offered a full assessment 19 summary letter. ETAU included liaison with the clinical team, especially around risk 21
issues with a clear safety protocol to alert clinicians, should suicidal or dangerous 22 23 ideation emerge. The use of ETAU as a control has the advantage of ensuring all trial 24
25 participants derive some benefit from the trial, ensuring that it conforms to the highest
26 ethical standards.
28 29 Analysis 30
31 The main aims of the feasibility study will be delivered both via the continued monitoring
32 of descriptive data and the analysis of data at the end of the last follow-up assessment.
34 This will include reporting data in line with the Consolidated Standards of Reporting Trials 35 36 (CONSORT) 2010 Statement, showing attrition rates and loss to follow-up. Analyses of 37
38 outcomes will not be focused on statistical significance, but will concentrate on descriptive
39 statistics and confidence intervals for treatment effects. The primary clinical outcome,
41 conversion to psychosis, will be examined using a discrete-time survival model. A detailed 42 43 statistical analysis plan will be produced prior to the examination of any of the outcome
44 data.
46 47 48 49
50 Results
51 Recruitment to the trial finished in August 2018 with a final sample of 70, with 34
53 individuals allocated to ETAU and 36 allocated to the Individual and Family Cognitive 54 55 Behavioural Therapy (IF CBT). The final sample of 70 represented 92% of the original 56 target sample size of 76. Each individual participant nominated a family member/carer to 58
take part, leading to an overall final sample of 140. Initially, participants were able to 59 60 nominate multiple family/carers (some nominating up to 3). However, it became
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1 2 3 apparent that this number of family/carer participants would not be feasible to follow up 4 5 within the study. Therefore, participants were required to choose just one family/carer 6
7 for the remainder of the study. 8 9 10 11
12 Demographic characteristics of the sample can be seen in table 2. Baseline variable
13 scores including CAARMS subscale scores for participants can be found in table 3.
15 Table 4 includes baseline variable scores for family member/carer. The initial 16 17 CONSORT diagram for entry into the trial is shown in figure 1. The CONSORT 18
19 highlights a high proportion of initial enquiries, with only a third referred. This may
20 reflect Early Intervention of Psychosis services that aim to meet the needs of those at-
22 risk of developing psychosis, those who have already experienced a first episode of 23 24 psychosis, as well as service-users reporting high levels of risk and disengagement. 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 3 [insert Table 2: Demographics and referral sources of participants in the IFCBT Trial ] 4 5 6 7 8 9 10 11
[insert Table 3: Baseline variable scores (main participant)]
13 14 15 16 17 18
[insert Table 4: Family member/carer baseline variable scores]
20 21
22 [insert Figure 1 CONSORT diagram for entry into the study ] 23 24 25 26 27 Discussion 28
29 The IF CBT study was a single rater, blind randomised feasibility study comparing individual and
30 Family CBT (IFCBT) plus enhanced treatment as usual (ETAU), to ETAU alone in people considered to 31 32 be at high risk of developing psychosis. This pilot feasibility study was in line with the research 33
34 recommendation in the NICE guidelines for psychosis and schizophrenia in children and young
35 people (NICE., 2014), which states a need to establish the clinical and cost effectiveness of a 36 37 combined family intervention with individual CBT for those considered to be at-risk of 38
39 developing psychosis. Previous meta-analysis (Davies et a., 2018) suggests conflicting results
40 regarding the efficacy of many trials and their tested treatments. As discussed, two studies examined
42 the potential for family interventions for ARMS with reduced rates of transition to psychosis in 43
44 comparison to usual care, fewer transitions and greater improvements in attenuated symptoms in 45 the FI group relative to control (Miklowitz et al., 2014), albeit, despite methodological shortcomings 47 of one study (Landa et al., 2014). In line with treatment recommendations from NICE 48 49 guidelines (2014), the current trial is the first of its kind that compares a combined approach of 50
51 individual and family intervention to usual care. This study provides a significant first step in
52 establishing the evidence base for such a combined intervention.
54 55 56
57 Our sample was mostly male, young and predominantly White British. This is a similar
58 sample profile to other ARMS studies (McGorry, 2014; Morrison et al., 2012),
60 although the lack of ethnic diversity in the sample may limit generalisability of findings to
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1 2 3 other ethnic groups. The majority of participants were eligible for the trial due to 4 5 experiencing attenuated psychotic symptoms and having moderately to severely impaired 6
7 functioning. Again, this is consistent with other trials of the ARMS population. 8 9 The study enabled referrals from voluntary sectors, self-referrals as well as NHS sector 10 11 organisations, enabling multiple entrances into the trial. Unlike other trials of interventions 12
13 for people at-risk of developing psychosis, referrals to the study were predominantly
14 from Early Detection and Intervention in Psychosis Services. The high number of
16 referrals received in the trial and those ineligible is likely to reflect the evolving role of Early 17 18 Intervention Services to meet the needs of those at-risk of developing psychosis, as 19 well as those who have already experienced a first episode of psychosis. In terms of 21
feasibility of future studies for young people with an at-risk mental state and indeed a 22 23 definitive trial of combined family and individual interventions, this evolution of Early 24
25 Intervention Services allows researchers to have a direct referral pathway for ARMS
26 populations from clinical services into research trials, allowing an efficient and effective way
28 to identify eligible participants and offer them the option of taking part in research. 29 30
31 Interestingly, despite the increased availability of support and intervention from these clinical
32 services, many young people still opted to take part in the research trial. Only 13% declined
34 to take part after being referred, with reasons varying from not help seeking, not being 35 36 interested in the research or personal reasons for not wanting to be involved. An additional 37
38 9% decided not to take part due to not wanting family member/carer involved in their care or
39 not having anyone they could nominate to be involved. The majority of young people chose
41 to nominate their parent as the family/carer in the study, although interestingly, a quarter of 42 43 participants chose to nominate a partner to take part in the intervention, which may suggest a
44 need for a partner/spouse specific intervention. In comparison to previous family studies,
46 other relatives and friends could be involved, who were deemed to have a particular 47 48 importance to the individual. This may complicate the specific family intervention and be 49
50 difficult to compare between individuals and groups, however it may be more reflective of
51 clinical need of individuals who wish significant
53 others to be involved in their care and treatment but not a parent. 54 55 56
57 There were no refusals to be randomised following assessment of eligibility. This low rate of
58 declines/refusals suggests the study and the intervention are highly acceptable to this group,
60 and therefore recruitment to a definitive trial would be feasible.
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1 2 3 4 5 The sample presented with high levels of comorbid emotional disorders such as moderate to 6
7 severe depression and high levels of social anxiety. This is highly consistent with the existing
8 literature and sample characteristics from other trials with the ARMS population (Fusar-Poli,
10 Nelson, Valmaggia, Yung, & McGuire, 2014) . CAARMS scores highlighted high levels of 11 12 distress in relation to symptoms, particularly on the non-bizarre ideas subscale. In addition to
13 high levels of comorbidity and distress for the individuals taking part in the study, some
15 nominated family members/carers also presented with moderate depression (BDI score 20-
16 17 28), anxiety and physical health problems. 18 19
Data collection was complete in June 2019 and we will report feasibility and 21
acceptability via retention rates, completion of the intervention, safety and qualitative 22 23 feedback as outlined in this paper and our statistical analysis plan following completion of 24
25 the trial. 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 3 4 5
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29 J. T. (2016). Development of a group and family-based cognitive behavioural therapy 30 31 program for youth at risk for psychosis. Early Interv Psychiatry, 10, 511–521.
32 Mari, J. D. J., & Streiner, D. L. (1994). An overview of family interventions and relapse on
34 schizophrenia: meta-analysis of research findings. Psychological Medicine, 24(3), 35 36 565-578. 37
38 McFarlane, W. R., Levin, B., Travis, L., Lucas, F. L., Lynch, S., Verdi, M., . . . Spring, E.
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45 McGlashan, T. H., Zipursky, R. B., Perkins, D., Addington, J., Miller, T., Woods, S. W., . . .
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48 patients prodromally symptomatic for psychosis. Am J Psychiatry, 163, 790–799. 49
50 McGorry, P. (2014). Preventive strategies in emerging mental disorders in young people:
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57 C., . . . Cannon, T. D. (2014). Family-focused treatment for adolescents and young
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16 17 psychosis: multisite randomised controlled trial. British Medical Journal, 344. 18
19 doi:10.1136/bmj.e2233 20
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22 Bentall, R. P. (2004). Cognitive therapy for the prevention of psychosis in people at 23 24 ultra-high risk: randomised controlled trial. Br J Psychiatry, 185, 291-297. 25
26 doi:10.1192/bjp.185.4.291 27
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29 high risk for psychosis population: clinical interpretation of findings and suggestions 30 31 for future research. Frontiers in psychiatry, 9, 502. doi:10.3389/fpsyt.2018.00502
32 NICE. (2014). Psychosis and schizophrenia in adults: Preventing Psychosis. Retrieved from
34 NICE clinical guidelines, London: 35 36 Nordentoft, M., Thorup, A., Petersen, L., Ohlenschlager, J., Melau, M., Christensen, T. O., . . 37
38 . Jeppesen, P. (2006). Transition rates from schizotypal disorder to psychotic disorder
39 for first-contact patients included in the OPUS trial. A randomized clinical trial of
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48 family interventions on relapse and rehospitalization in schizophrenia—a meta- 49
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10 212–219. 11 12 Tor, J., Dolz, M., Sintes, A., Muñoz, D., Pardo, M., de la Serna, E., . . . Baeza, I. (2017).
13 Clinical high risk for psychosis in children and adolescents: a systematic review.
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16 17 Urben, S., Pihet, S., Jaugey, L., Halfon, O., & Holzer, L. (2012). Computer-assisted cognitive 18
19 remediation in adolescents with psychosis or at risk for psychosis: A 6-month follow-
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22 van der Gaag, M., Smit, F., Bechdolf, A., French, P., Linszen, D. H., Yung, A. R., . . . 23 24 Cuijpers, P. (2013). Preventing a first episode of psychosis: meta-analysis of 25
26 randomized controlled prevention trials of 12 month and longer-term follow-ups. 27
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29 Woods, S. W., Breier, A., Zipursky, R. B., Perkins, D. O., Addington, J., Miller, T. J., . . . 30 31 Tohen, M. (2003). Randomized trial of olanzapine versus placebo in the symptomatic
32 acute treatment of the schizophrenic prodrome. Biological Psychiatry, 54(4), 453-464.
34 Yung, A. R., Stanford, C., Cosgrave, E., Killackey, E., Phillips, L., Nelson, B., & McGorry, 35 36 P. D. (2006). Testing the ultra high risk (prodromal) criteria for the prediction of 37
38 psychosis in a clinical sample of young people. Schizophrenia Research, 84(1), 57-66. 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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Pe e r
39
1 2 3 Table 1 Assessment schedule 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 Abbreviations: CAARMS (Comprehensive Assessment of At Risk Mental States); SOFAS
40 (Social and Occupational Functioning Assessment Scale); EQ-5D (Health Questionnaire);
41 GHQ (General Health Questionnaire); BDI (Beck Depression Inventory); SIAS (Social
42 Interaction Anxiety Scale); PSWQ (Penn State Worry Questionnaire); FMSS (Five Minute 43
44 Speech Sample); FQ (Family Questionnaire); ECR-RS (Relationship Structures); PCPW
45 (Perceived Criticism and Warmth Questionnaire). 46
Measure Baseline 6 months 12 month
Individual Family Individual Family Individual Family
CAARMS ✓
✓
✓
SOFAS ✓
✓
✓
EQ-5D ✓ ✓ ✓ ✓ ✓ ✓
GHQ ✓ ✓
✓ ✓
Time Use Interview
✓
✓
✓
BDI ✓ ✓ ✓ ✓ ✓ ✓
SIAS ✓ ✓ ✓ ✓ ✓ ✓
PSWQ ✓ ✓ ✓ ✓ ✓ ✓
FMSS ✓
✓
✓
FQ ✓ ✓ ✓ ✓ ✓ ✓
ECR-RS ✓ ✓ ✓ ✓ ✓ ✓
PCPW ✓ ✓ ✓ ✓ ✓ ✓
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1 2 3 Table 2: Demographics and referral sources of participants in the IFCBT Trial 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Variables of Interest N (%) or M (SD)
N = 70
Age at entry Range (years)
22.2 (4.9) (16-35)
Male:Female ratio 42:28
Ethnicity
White 61 (87.14%) Mixed 4 (5.71%) Asian 3 (4.29%) Other 2 (2.86%)
Highest Education
Primary (school) 9 (12.9%) Secondary (GCSEs) 30 (42.9%) Further (A levels) 22 (31.4%) Higher (University) 9 (12.9%)
Relationship with Other
Parent 43 (61.4%) Other relative 3 (2.9%) Partner 18 (25.7%) Friend or Other (E.g. neighbour) 6 (5.7%)
Living Arrangements
Parents 20 (28.6%) Partner 13 (18.6%) Alone 5 (7.1%) Parents and Siblings 20 (28.6%) Other (e.g. friends) 12 (15.7%)
Previous Receipt of CBT
Yes 23 (32.9%) No 46 (65.7%)
Referral Source
Early Detection / Intervention in Psychosis Service 51 (72.9%) Substance Misuse 5 (7.1%) CAMHS 1 (1.4%) College 1 (1.4%) Self-referral 4 (5.7%) IAPT Plus 1 (1.4%) Employment Support 2 (2.9%) Primary Care 2 (2.9%) Other e.g. previous engagement in research 3 (4.3%)
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1 2 3 Table 3: Baseline variable scores (main participant) 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46
Variable n Percentage or M (SD)
CAARMS subgroup at entry to trial
Attenuated Psychosis
56 80%
ARMS Vulnerability
3 4.3%
ARMS BLIPS 0 -
More than one ARMS group
11 15.7%
SOFAS total 70 43.09 (9.75)
BDI total 69 28.1 (13.3)
SIAS total 69 42.9 (15.9)
EQ5D health state mean 69 56.4 (23.18)
CAARMS subscale scores N Whole sample M (SD)
N Only participants experiencing the phenomenon M (SD)
Unusual thought content severity
70 2.5 (1.82) 52 3.37 (1.22)
Unusual thought content frequency
70 2.59 (1.92) 52 3.48 (1.35)
Unusual thought content distress
67 39.40 (38.20) 49 53.88 (34.78)
Non-bizarre ideas severity
70 3.07 (1.47) 63 3.41 (1.10)
Non-bizarre ideas frequency
70 3.50 (1.54) 63 3.89 (1.05)
Non-bizarre ideas distress
69 61.12 (36.31) 62 68.02 (31.51)
Perceptual abnormalities severity
70 3.50 (1.48) 63 3.89 (0.95)
Perceptual abnormalities frequency
70 2.89 (1.37) 63 3.21 (1.02)
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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58
Perceptual abnormalities distress
68 53.13 (37.96) 61 59.23 (35.24)
Disorganised speech severity
70 1.57 (1.10) 52 2.12 (0.68)
Disorganised speech frequency
67 2.67 (1.93) 49 3.65 (1.20)
Disorganised speech distress
67 33.94 (38.40) 49 46.41 (37.90)
Aggression severity
70 2.86 (1.51) 63 3.17 (1.23)
Aggression frequency
69 3.17 (1.61) 62 3.53 (1.26)
Suicidality severity
70 2.37 (1.53) 54 3.07 (0.93)
Suicidality frequency
67 2.27 (1.85) 51 2.98 (1.53)
Page 25 of 26
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1 2 3
4 Table 4: Family member/carer baseline variable scores
6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Variables n M (SD) or N (%)
BDI total 69 11.97 (13.09),
SIAS total 69 22.83 (15.36)
EQ-5D Dimension
Mobility 69
No problems 54 (78.3%) Problems 15 (21.7%)
Self-care 69
No problems 65 (94.2%) Problems (N, %) 4 (5.8%)
Usual Activity 69
No problems 53 (76.8%) Problems 16 (23.2%)
Pain / discomfort 69
No problems 43 (62.3%) Problems 26 (37.7%)
Anxiety / depression 69
No problems 40 (58.0%) Problems 29 (42.0%)
Health State Mean 69 71.99 (18.87)
ECR-RS 69
Attachment related avoidance 20.94 (8.15) Attachment related anxiety 7.48 (5.45)
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Review
1 2 3 Figure 1 CONSORT diagram for entry into the study 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58
Excluded/decline at referral (n=65)
- Not want family involved (n= 13)
- Participant declined after referral (n= 12)
- No interest in research (n= 9)
- Over/Under age criteria (n= 6)
- Unable to contact once referred (n= 5)
- Unsuitable for the study due to risk (n=4 )
- Antipsychotic medication (n= 3)
- Not have family to nominate (n= 2)
- Family declined involvement (n= 2)
- Not help seeking (n=2)
- Already at FEP (n=1)
- Other reasons (n= 6)
Referrals (n=173)
Initial Enquiries (n=529) Excluded/decline at initial enquiry (n=356)
- Already at FEP (n= 82)
- Over/Under age criteria (n= 75)
Under 16 (n=26)
Over 35 (n= 49)
- Disengaged from services (n= 62)
- Family element (n= 29)
-Family decline (n= 1)
-Individuals not want family involved (n= 19)
-Individuals did not have family to nominate
(n= 9)
- below ARMS threshold (n=28)
- No reason but decline (n=20)
- In receipt of antipsychotics past / present (n= 15)
- Not interested in research (n= 12)
- Interpreter needed (n= 9 )
- No drop in functioning (n=3)
Assessed (n=108)
Randomised (n=70)
Ineligible at baseline (n=38)
- Already at FEP (n= 23)
- Below ARMS threshold (n= 7)
- No drop in functioning (n= 2)
- Antipsychotic medication (n=1)
- family member declined (n=1)
- Not helpseeking (n=1)
- baseline not completed (n=1)
- possible organic impairment (n=1)
- Decline at baseline (n=1)