Trans-diagnostic Group CBT vs. Standard Group CBT for Depression, Social Anxiety and Agoraphobia/Panic Disorder: A Pragmatic, Multicenter Non-inferiority Randomized Controlled Trial
Phase: NA
Conditions: Depression, Unipolar, Anxiety Disorder Social, Panic Disorder
Sponsor: Psychiatric Research Unit, Region Zealand, Denmark

STUDY PROTOCOL
Open Access
Transdiagnostic group CBT vs. standard
group CBT for depression, social anxiety
disorder and agoraphobia/panic disorder:
Study protocol for a pragmatic, multicenter
non-inferiority randomized controlled trial
Sidse M. Arnfred1,5*, Ruth Aharoni2, Morten Hvenegaard1, Stig Poulsen3, Bo Bach1, Mikkel Arendt4,
Nicole K. Rosenberg2 and Nina Reinholt2,5
Abstract
Background: Transdiagnostic Cognitive Behavior Therapy (TCBT) manuals delivered in individual format have been
reported to be just as effective as traditional diagnosis specific CBT manuals. We have translated and modified the
“The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders” (UP-CBT) for group delivery in Mental
Health Service (MHS), and shown effects comparable to traditional CBT in a naturalistic study. As the use of one
manual instead of several diagnosis-specific manuals could simplify logistics, reduce waiting time, and increase
therapist expertise compared to diagnosis specific CBT, we aim to test the relative efficacy of group UP-CBT and
diagnosis specific group CBT.
Methods/design: The study is a partially blinded, pragmatic, non-inferiority, parallel, multi-center randomized
controlled trial (RCT) of UP-CBT vs diagnosis specific CBT for Unipolar Depression, Social Anxiety Disorder and
Agoraphobia/Panic Disorder. In total, 248 patients are recruited from three regional MHS centers across Denmark
and included in two intervention arms.
The primary outcome is patient-ratings of well-being (WHO Well-being Index, WHO-5), secondary outcomes include
level of depressive and anxious symptoms, personality variables, emotion regulation, reflective functioning, and social
adjustment. Assessments are conducted before and after therapy and at 6 months follow-up. Weekly patient-rated
outcomes and group evaluations are collected for every session. Outcome assessors, blind to treatment allocation, will
perform the observer-based symptom ratings, and fidelity assessors will monitor manual adherence.
Discussion: The current study will be the first RCT investigating the dissemination of the UP in a MHS setting, the UP
delivered in groups, and with depressive patients included. Hence the results are expected to add substantially to the
evidence base for rational group psychotherapy in MHS. The planned moderator and mediator analyses could spur
new hypotheses about mechanisms of change in psychotherapy and the association between patient characteristics
and treatment effect.
(Continued on next page)
* Correspondence: sidar@regionsjaelland.dk
1Psychiatric Hospital Slagelse & Psychiatric Research Unit, Region Zealand
Psychiatry, Faelledvej 6, Building 3, Level 4., DK-4200 Slagelse, Denmark
5Institute of Clinical Medicine, Faculty of Health Sciences, University of
Copenhagen, Copenhagen, Denmark
Full list of author information is available at the end of the article
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Arnfred et al. BMC Psychiatry  (2017) 17:37 
DOI 10.1186/s12888-016-1175-0

(Continued from previous page)
Trial registration: Clinicaltrials.gov NCT02954731. Registered 25 October 2016
Keywords: Cognitive Behavior Therapy, Depression, Anxiety, Negative Affect, Clinical Trial, Unified Protocol, Change
Mechanisms, Session Tracking
Background
Unipolar depression and anxiety disorders are the most
prevalent - and often co-occurring - psychiatric disorders in
primary health care [1, 2]. These disorders are frequently
associated with a chronic, disabling course, functional im-
pairment, and high socio-economic costs [3, 4]. From this
perspective, it is imperative to improve mental health ser-
vice (MHS) treatment programs for these disorders.
Recently, transdiagnostic CBT (TCBT) manuals (e.g.[5,
6]), which employ the same set of treatment principles
across several mental disorders (i.e. anxiety disorders and
unipolar depression), have been developed to improve the
clinical utility of standard diagnosis-specific CBT programs
(STD-CBT) [7]. TCBT has demonstrated promising
treatment effects comparable to STD-CBT [8, 9]. Poten-
tially, TCBT deals effectively with comorbidity often seen
in MHS, reduces waiting time for patients, and reduces
training demands and costs for the clinicians. Moreover,
principal and comorbid disorders are treated simultan-
eously, several disorders are treated in the same psycho-
therapy group, and the clinician only need to be trained in
one manual rather than several manuals for different
disorders [10, 11].
The “Unified Protocol for Transdiagnostic Treatment
of Emotional Disorders” (UP) [12, 13] is one of the most
widely studied transdiagnostic manuals [14]. In a recent
systematic review and meta-analysis of TCBT for anxiety
disorders (including 12 trials, N = 1933), TCBT was asso-
ciated with an overall positive outcome, performed bet-
ter than waitlist- and treatment as usual comparison
interventionsand demonstrated durable treatment gains
through follow-up [15]. The pooled treatment effect was
moderate (experimental vs control treatment effect size
Cohens d = .68; [95%CI: 0.45-0.90; p < .001) [15]. Large-
scale, high quality randomized controlled trials (RCT) are
still warranted in order to establish a more solid evidence
base concerning the relative efficacy of TCBT and STD-
CBT. Individual UP therapy has resulted in reduction of
anxiety and depression symptoms for patients with comor-
bid anxiety disorders in two open trials [16] and one RCT
using wait-list comparator [17] as well as one large-scale
RCT comparing UP with STD-CBT for anxiety disorders
(Barlow 2016, personal communication). Less evidence ex-
ists for the effect of UP on depressive disorders, but data
from the anxiety trials suggest improvement in comorbid
conditions [18]. Limited, but promising, data, including our
own naturalistic study suggest that the UP can be delivered
in groups with pre-post effect sizes in the medium to large
range [19–22]. This is important, as the group format is an
efficacious and cost-effective way of delivering treatment
[23], which is regularly used in Danish MHS.
Neuroticism/negative affectivity (defined as the tendency
to experience frequent and intense negative emotions, in-
cluding anxiety, fear, anger, sadness, and the like) has been
recognized as an important temperamental dimension in
major conceptualizations of personality (i.e. the Big Five
Model [24]; The Alternative DSM-5 Model for Personality
Disorders [25]). Further, findings from recent research sug-
gest that neuroticism is a prominent transdiagnostic factor
in the development of emotional disorders [7, 26], which
predicts the course of the disorders as well as treatment
effect [27]. UP targets neuroticism itself and prelimin-
ary findings suggest that negative affectivity is reduced
following treatment with the UP [28, 29]. Accordingly,
we will investigate whether UP-CBT improves negative
affectivity and emotion regulation strategies to a larger
extend than STD-CBT.
Mechanisms of change
To ensure that a treatment effect can be attributed to
the hypothesized active ingredients of the specific treat-
ment it is necessary to monitor the fidelity of the imple-
mentation of the treatment. Measuring treatment fidelity
involves monitoring adherence to a specific treatment
manual, assessment of sufficient differentiation between
treatment manuals, and assessment of therapist compe-
tence, i.e. the level of clinical skills involved in the dis-
semination of the treatment. Fidelity must be assessed
by trained external evaluators, who review a sample of
session recordings, and evaluate these three aspects of fi-
delity by the use of a fidelity rating scale relevant to the
specific treatment [30].
Studies suggest that various in-session factors, aside
from the specific therapeutic method, contribute to up
to 30% of the therapeutic change [31]. We still need a
better understanding of what these factors are and how
they contribute to treatment outcome [30, 32]. It is already
well established that the quality of the therapeutic re-
lationship between the patient and the therapist, and
specifically the therapeutic alliance, influence treatment
outcome [33, 34]. Likewise, in group psychotherapy rela-
tional factors such as group cohesion and a positive group
climate are associated with outcome. In STD-CBT the
patients have easy access to identification with and
Arnfred et al. BMC Psychiatry  (2017) 17:37 
Page 2 of 14

understanding of group member’s symptoms. This might
be different when the group consists of patients with dif-
ferent diagnoses. Hence, we explore in more detail aspects
of the therapeutic relationship between group members.
Objectives
The main objective is to investigate the effects of group
UP-CBT compared with STD-CBT for psychiatric outpa-
tients with a primary diagnosis of Unipolar Depression
(DEP), Social Anxiety Disorder (SAD) or Agoraphobia/
Panic Disorder (Ag/PD). Main outcomes are subjective
well-being, symptom levels, personality traits, emotion
regulation, perseverative thinking, and social adjustment.
Apart from the primary outcomes, we aim to investigate
whether UP-CBT, as proposed, confers changes in nega-
tive and positive affectivity and emotion regulation strat-
egies, and, if so, whether these changes are larger in the
UP-CBT than in the STD-CBT treatment. Furthermore,
we will explore the possible mediating role of treatment
factors, including manual adherence and group rela-
tional factors, on outcome. Lastly, we will investigate po-
tential moderators of outcome, i.e. patient characteristics
like comorbidity, personality traits, reflective function,
social network, and adverse life events across and within
treatment conditions.
Hypotheses
We hypothesize that subjective well-being and symptom
levels are equally improved following group UP-CBT and
group STD-CBT. Based on the treatment target in UP-
CBT, we hypothesize that negative affectivity will decrease
and emotion regulation strategies will be improved to a
higher degree following UP-CBT compared with STD-
CBT. We hypothesize that group climate is equivalent in
the two arms, and that this and manual adherence medi-
ates a positive outcome. Hypothetical directions of effect
of moderators are listed in Table 1.
Methods/design
Design
The current trial is an investigator-initiated, partially
blinded, pragmatic, parallel, non-inferiority, multi-center
randomized clinical trial (RCT). Two equally sized inter-
vention arms, UP-CBT and STD-CBT, are compared. In
total, we include 248 patients recruited from three Da-
nish regional MHS. A CONSORT diagram is provided
in Fig. 1. Data management is purely digital and is managed
by a private enterprise, EasyTrial©, who also assists with
randomization, treatment allocation and concealment.
Settings
The three Danish MHS clinics participating in the study
conduct CBT groups for anxiety disorders and/or de-
pression and have previously been engaged in clinical
trials. Psychotherapeutic Clinic, Mental Health Centre
Copenhagen is located in the inner center of the Capital,
the Outpatient Clinics at Risskov Psychiatric Hospital is
located in Aarhus, and Psychiatric Outpatient Clinic in
Slagelse is located on the isle of Zealand. The number of
attending patients and staff is lower at the Slagelse loca-
tion, hence the sites contribute unequally to the trial. In
total, 1400 patients with depression and 550 patients
with relevant anxiety disorders attend the participating
MHS clinics per year. The clinic in Copenhagen has
piloted the UP-CBT as group therapy and two of the re-
searchers have hands-on experience with group UP-CBT
and training of UP-CBT therapists for the pilot trial.
Participants
We aim to include 248 patients that satisfy the inclusion
criteria: (1) a principal DSM-5 diagnosis of DEP (single
episode or recurrent) (app. 50%), SAD (app. 25%), and
Ag/PD (app 25%), (2) age 18-65 years, (3) the patient is
currently not using any antidepressants or use accepted
antidepressants (according to a predefined protocol,
available on request), which have been unchanged for at
least 4 weeks before intervention onset and no change
in antidepressants is anticipated, (4) sufficient knowledge
of the Danish language. Patients will be excluded if (1)
risk of suicide is high or moderate according to clini-
cians or assessment researchers, (2) they have alcohol or
drug dependency, (3) they are diagnosed with a cluster
A or B (DSM-5) personality disorder by intake clinicians
Table 1 Hypothesized effects of moderators in TRACT-RCT
Moderator
UP-CBT>
STD-CBT
Outcomea
Comorbidity
+
-
Personality Inventory for DSM-5 SF
Antagonism
0
-
Personality Inventory for DSM-5 SF
Psychoticism
0
-
Personality Inventory for DSM-5 SF
Detachment
+
-
Personality Inventory for DSM-5 SF
Negative Affect
+
-
Personality Inventory for DSM-5 SF
Disinhibition
+
-
Life Event Checklist for DSM-5 (LEC-5)
0
-
Level of Personality Functioning (LPFS-BF)
0
+
Copenhagen Social Relations
Questionnaire (CSRQ)b
0
+
Reflective Function Questionnaire (RFQ)
-
+
The first colon is read: “when the participants have high levels of the
moderator, treatment effect is larger in UP-CBT compared to STD-CBT”. The
second colon is read: “when the moderator is high outcome is + (good)
or - (bad)”. 0 = no effect/difference between interventions
aWHO-5
bPositive/supportive relationships
Arnfred et al. BMC Psychiatry  (2017) 17:37 
Page 3 of 14

or assessment researcher, (4) they have co-morbidity of
pervasive developmental disorder, psychotic disorders,
eating disorders, untreated attentional disorder, bipolar
disorder, or severe physical illness, (5) they receive
psychopharmacological treatments other than those
predefined as acceptable, (6) they receive concurrent
psychotherapy, (7) they do not accept to stop the use of
anxiolytics within the first four weeks of intervention.
Recruitment procedure and baseline assessment
Patients are typically referred by general practitioners,
when they have failed to respond to one or two different
treatments (medication and/or psychotherapy). During
intake, the patients will be evaluated by clinicians to be
eligible for psychotherapeutic treatment in regional
MHS as part of the standard procedure in the psycho-
therapeutic unit and they will be screened for eligibility
according to the above described criteria. If patients are
eligible for treatment, they will be approached for par-
ticipation and provided with information about the
project. Patients who cannot or will not participate in
the study will be offered treatment as usual, i.e. group
STD-CBT.
Patients who accept participation, will receive an invi-
tation for further assessment using Mini International
Neuropsychiatric Interview ((MINI, v 7.0 for DSM-5)
and if eligibility is confirmed, informed consent is ac-
quired. In the same consultation, supplementary baseline
ratings and administration of the web-based patient ques-
tionnaires on stable patient characteristics, hypothesized
to moderate outcome, are performed (see Table 2 for an
overview of procedures and time points). Next, after
randomization and blinding (see below), within 3 weeks of
intervention onset additional baseline ratings are gathered
by an outcome assessor making telephone-based inter-
views and encouraging the patient to answer the web-
based outcome assessment questionnaires.
Randomization and blinding
Randomization is performed in blocks of 4 participants,
stratified by diagnosis and site, when 16 patients (8 with
DEP and 4 with SAD and 4 with Ag/PD) are included
(see study flow chart, Fig. 1). EasyTrial © perform the
randomization and intervention allocation of study par-
ticipants. Allocation to experimental intervention or
comparison intervention will be computer-generated. In
psychotherapy trials, therapists and patients cannot be
blinded to intervention type. However, the researcher
designated to report the main intervention effects (NR)
will be blind to treatment allocation and will not partici-
pate in the treatment of study patients. As NR is the
only Danish certified UP supervisor she is, however, in
charge of UP-CBT training (see below) and continuous
supervision of study therapists. The latter will be based
on verbal report, and the therapists will be instructed to
anonymize the patients in their reports (leaving out
name, specific age and other identifiers). EasyTrial© is
designed with several access layers, where the data ad-
ministrators have full access to all data, researchers have
access to entered information and treatment allocation,
Fig. 1 CONSORT Flow diagram TRACT-RCT. UP-CBT: The experimental intervention “Unified Protocol” group CBT. STD-CBT: The comparator
intervention standard CBT i.e. diagnosis specific group CBT applying evidence-based protocols
Arnfred et al. BMC Psychiatry  (2017) 17:37 
Page 4 of 14

while outcome assessors and NR have limited access,
only having lists with names of participants, their timelines
and contact details. In this manner, outcome assessors and
NR will be blinded to treatment allocation. Furthermore,
outcome assessors and NR will not participate in any
clinical routines in the clinic. The patients are asked not
to discuss their therapy with the outcome assessors and
they will not communicate with the therapists. Outcome
assessors are asked to guess about treatment allocation
after the interviews to be able to analyze possible bias.
For the statistical analyses of intervention effects,
intervention type is concealed in the data extraction
Table 2 Overview of procedures and measurements TRACT-RCT
Trial Schedule
Inclusion
Allocation
Post-allocation
Time points (weeks)
w-3a
w0
w1-2
w4-18
w19
w45
Enrollment
MINI
x
SAPAS
x
Eligibility screen
x
Informed consent
x
Contact details
x
Web system entrance
x
Randomization
x
Intervention arm allocation
x
CBT group allocation
x
Interventions
UP-CBT
x-x
STD-CBT:
DEP-CBT
x-x
SAD-CBT
x-x
AG/PD-CBT
x-x
Assessments
Observer ratings
Demography
x
Medical History
x
Medication History
x
x
x
Hamilton Anxiety Rating Scale HAM-A6
x
x
x
Hamilton Depression Rating Scale HAM-D6
x
x
x
MINI (brief)
x
x
Therapist ratings
Session Settings
x-x
Manual Adherence Checklist
x-x
Group evaluation
x
Patient questionnaires
History & Characteristics
x
Main Outcomes
x
(x) b
x
x
Weekly Outcomes
x
x-x
Session evaluations
x-x
Group evaluation
x
Medicine & Suppl. Treatment
x
x
For detailed overview of patient questionnaires see Table 3, for description of rating scales see text
aInclusion interview will be performed close to patient intake at the clinic and we expect some waiting time before group onset date (not depending on
intervention arm) can be established
bPrimary outcome, WHO-5, is included in both “Weekly outcomes” and “Main outcomes”
Arnfred et al. BMC Psychiatry  (2017) 17:37 
Page 5 of 14

from EasyTrial©. The analysis of the primary outcome
will be conducted with treatment allocation blinded.
The intervention and control arm will randomly be
coded as “A” and “B” and the deciphering will not be
done before conclusions have been formulated based
on these codes.
Interventions
The experimental treatment, group UP-CBT, consists of
8 treatment modules delivered in 14 group sessions
given weekly in 2 h sessions. The group manual has been
modified from a Danish translation of the published UP
for individual therapy [5, 13] and recommendations on
group delivery from the UP Institute, Center for Anxiety
and Related Disorders (CARD), Boston University. (per-
sonal communications) [22].
The SAD STD-CBT manual is based on the main
principles described in the individual CBT manual by
[35] and the PD/Ago STD-CBT manual is based on the
principles described in the individual CBT manual by
[36]. The manuals are adapted for use in Danish MHS
settings and in groups. The two anxiety manuals are
supplemented with frequently used Danish CBT hand-
outs from [37, 38].
The DEP STD-CBT manual is based on a Danish
group CBT manual for depression [39]. The manual has
previously been used in research studies in Danish MHS
[40], and is in line with the interventions described in an
American manual [41]. In order to adjust the manual to
the settings of group therapy in the TRACT-RCT, an
individual group preparation session was added as well
as 2 extra group sessions (session 7 and session 12).
The work sheets added for these extra sessions are
based on [37].
Treatment intensity (number and duration of group
sessions) will be equal in both treatment arms. Psychi-
atric evaluation, extraordinary individual sessions and
supplementary occupational counselling or physiother-
apy are possible in both intervention arms.
Intervention fidelity
In both intervention arms the therapists will be mental
health professionals, and in each group at least one ther-
apist will have one-year CBT training and have partici-
pated in the pre-trial workshops. UP-CBT therapists
attend a two-day UP-CBT workshop conducted by a cer-
tified Danish UP therapist (NR). Certification is granted
after satisfactory intensive audio-tape supervision of a full
pre-trial group course. During the intervention UP-CBT
therapists from all sites receive SKYPE©-based monthly
group supervision (2 h) by NR. The therapists delivering
UP-CBT will not be conducting STD-CBT. STD-CBT-
therapists attend a one-day workshop on each of those
manuals they will be delivering. The workshops are
offered to secure alignment of STD-CBT manuals
across sites, and STD-CBT therapists conduct pre-trial
STD-CBT groups according to the recommended man-
uals. During the intervention STD-CBT therapists from
each standard group receive SKYPE©-based monthly
group supervision (2 h) by a CBT specialist and supervisor.
The therapists delivering STD-CBT will not conduct
UP-CBT.
In both intervention arms, group sessions will be audio
monitored, and random samples (20%) will be rated for ad-
herence to UP-CBT or STD-CBT manual and techniques
and therapist competence. For UP fidelity the Therapist Ad-
herence Rating Scale (Barlow, personal communication,
2016) is applied. For the STD-CBT groups, manual adher-
ence and therapist competence will be measured by manual
specific adherence and competence rating scales, based on,
or in case of DEP, inspired by, those previously used by Pro-
fessor Barlow’s research group [42]. All therapists also carry
out self-monitoring of CBT techniques as they check a
list of specific interventions after each group session
(see below). Additionally, information regarding non-
specific program adherence such as waiting time, stability
of therapists, session cancellation, delay etc. will be col-
lected at each session.
Assessment
Data are gathered through a number of ratings from pa-
tients, therapists and observers prior to inclusion, weekly
throughout the intervention period, at the end of ther-
apy, and at 6 months follow-up. An overview of assess-
ment procedures is given in Table 2, and instruments in
each category are detailed below. Outcome assessors are
medical or psychology students, who will be certified in
the use of relevant rating scales and will be trained to
excellent agreement on the observer instruments by ex-
perienced psychotherapy researchers prior to inclusion
start and with continuous monthly co-ratings and reli-
ability assessments based on audiotaped interviews.
Main outcomes are collected by outcome assessors along
with patient self-ratings at end of the intervention and at
6 months follow-up. Every week, patients and therapists
will fill out brief questionnaires immediately before and
after the group session. If participants discontinue the
intervention, we will attempt to gather all data, except
those relating to intervention participation (session rat-
ings, therapy evaluation), unless the patient explicitly de-
nies participating in data collection (Table 3).
Primary outcome
Who Well-Being Index (WHO-5)
The primary outcome is the self-rating instrument
WHO Well-Being Index, 5 items (WHO-5). It is tracked
weekly during treatment, at the end of treatment and
at follow-up. It is a short questionnaire used to access
Arnfred et al. BMC Psychiatry  (2017) 17:37 
Page 6 of 14

subjective well-being. It is derived from a 28-item Psycho-
logical Well-Being Schedule, where the five items indicat-
ing general well-being produced a unidimensional positive
dimension of well-being. The raw scores are transformed
to a score from 0 (worst thinkable well-being) to a 100
(best thinkable well-being). A score <50 suggests poor
emotional well-being and scores ≤28 indicate depression
[43]. The WHO-5 Well-being Index has demonstrated
high reliability, validity and sensitivity to treatment re-
sponse for affective and neurotic disorders in psychiatric
care [44, 45]. It is considered a very sensitive outcome
measure as it does not incorporate negative quality of life,
i.e. distress, and has no ceiling effect [46].
Secondary outcomes
Observer ratings
These ratings are performed by researchers (clinical psy-
chologists) at baseline and by outcome assessors at later
time points. The telephone based outcome assessment
will also provide opportunity for coaching the patient to
fill out self-report questionnaires.
Mini International Neuropsychiatric Interview (mini)
MINI was developed by Sheehan and Lecrubier in 1992.
MINI, v. 7.0 for DSM-5 will be applied. Version 7.0 con-
tains 17 modules for the major axis I psychiatric disorders
in DSM-IV-TR and ICD-10. MINI is validated against
Table 3 Patient Questionnaires
Questionnaires for Patients
Inclusion
Allocation
Baseline
Group therapy
End of group
Follow-up
Timepoint (week number)
w-3
w0
w1-2
w4-18
w19
w45
History & Characteristics
Personality Inventory for DSM-5 Short Form (PID-5 SF)
x
Level of Personality Functioning – Brief Form (LPFS-BF)
x
Life Event Checklist for DSM-5 (LEC-5)
x
Copenhagen Social Relations Questionnaire (CSRQ)
x
x
Reflective Function Questionnaire (RFQ-54)
x
Main Outcomes
WHO Well-Being Index (WHO-5)
x
x-x
x
x
Hopkins Symptom Check List (SCL-25)
x
x
x
Positive Affect and Negative Affect Schedule (PANAS)
x
x
x
Emotion Regulation Questionnaire (ERQ)
x
x
x
Emotion Regulation Strategies Questionnaire (ERSQ)
x
x
x
Perserverative Thinking Questionnaire (PTQ)
x
x
x
Becks Depression inventory (BDI-II)
x
x
x
Work and Social Adjustment Scale (WSAS)
x
x
x
Personality Inventory for DSM-5 (PID-5-SF) Internalizing Features
x
x
Client Satisfaction Questionnaire (CSQ)
x
Depending on primary anxiety diagnosis:
Panic Disorder: Panic Disorder Severity Scale (PDSS)
x
x
x
Social Anxiety Disorder: Liebowitch Social Anxiety Scale (LSAS)
x
x
x
Agoraphobia: Mobility Inventory for Agoraphobia (MIA)
x
x
x
Weekly Outcomes
Overall Anxiety Severity and Impairment Scale (OASIS)
x
x-x
Overall Depression Severity and Impairment Scale (ODSIS)
x
x-x
Homework Tracker (HWT)
x-x
Session evaluations
Group Questionnaire 12-items (GQ12)
x-x
Group evaluation
Evaluation of the course of therapy
x
Medicine & Suppl Treatment
Purpose-made questions
x
x
x
Arnfred et al. BMC Psychiatry  (2017) 17:37 
Page 7 of 14

SCID-P for DSM-IV and CIDI for ICD-10 [47]. Psycho-
metric analyses of the MINI have demonstrated acceptable
test-retest and inter-rater reliability. MINI is divided into
modules identified by letters (A-P), each corresponding to
a diagnostic category. At the enrolment interview we in-
clude all modules but P, and use the diagnostic assessment
for eligibility evaluation and description of comorbidity.
At end of therapy and follow-up we only use modules A,
D, E and F for assessment of recovery or relapse of pri-
mary diagnoses.
Standardized Assessment of Personality – Abbreviated
Scale (SAPAS) MINI assessment will be supplemented
with SAPAS as a screening for comorbid personality
problems. It consists of eight items scoring 0 or 1, sum-
ming up to a maximum of 8. A score of 3 and above has
been shown to predict DSM-IV personality disorder
diagnosis [48].
Hamilton Anxiety Rating Scale HAM-A6 HAM-A6 is
a focused version of the original 14-item Hamilton Anxiety
Scale (HAM-A) [49]. It covers six symptoms of anxiety dis-
orders as one homogenous factor (total score) with high
discriminant validity in outcome studies [50–52].
Hamilton Depression Rating Scale HAM-D6 HAM-D6
is based on the original 17-item Hamilton Depression
Rating Scale [53]. Item analyses have shown that the six
included items validly reflect a global depression assess-
ment by experts and a total HAM-17 score [54, 55].
Patient self-ratings
The secondary patient rated outcomes are measured at
baseline, at end of treatment and at follow-up. Three
scales are only presented for those patients with the
diagnosis: PD: Panic Disorder Severity Scale (PDSS); Ag:
Mobility Inventory for Agoraphobia (MIA); SAD: Lie-
bowitz Social Anxiety Scale – Self-Report (LSAS-SR).
Hopkins Symptom Checklist (SCL-25) SCL-25 is a
widely-used questionnaire of self-reported psychological
symptoms and psychological distress, which has been
used in clinical screening and outcome research [56, 57].
It exists in several formats from 6 to 92 items. In the
current study, one of the original brief versions consist-
ing of 25 items, tracking two of the original nine symp-
tom dimensions (depression and anxiety) is used [58].
The Positive and Negative Affect Schedule (PANAS)
PANAS [59] is included as a secondary outcome meas-
ure of negative and positive affect. PANAS is a brief,
valid, and reliable self-report measure of core negative
affect and deficits in positive affect. It consists of 20
emotion words, which are rated on a scale from 0 (very
slightly or not at all) to 5 (extremely), indicating the ex-
tent to which the patient experienced the emotion past
week. PANAS has shown high internal consistency, sta-
bility and validity [60]. The subscales also showed ac-
ceptable to good internal consistencies (negative affect:
α = .78; positive affect: α = .85).
Emotion Regulation Questionnaire (ERQ) ERQ is a
10-item instrument, which assesses the typical use of
two general emotion regulation strategies: emotion sup-
pression (i.e. ‘I keep my emotions to myself’) and re-
appraisal (i.e. “When I want to feel less negative emotion, I
change the way I'm thinking about the situation”). The
items are rated on a 7-point Likert scale from 1 (strongly
disagree) to 7 (strongly agree). The scale has been shown
to possess good psychometric properties [61].
Emotion Regulation Strategies Questionnaire (ERSQ)
ERSQ is a 27-item self-report instrument that measures
the use of emotion-regulation skills during the previous
week on a five-point Likert scale (“not at all” to “almost
always”). The questionnaire includes nine scales measur-
ing different emotion regulation skills (i.e. ‘I paid attention
to my feelings’; ‘I was able to accept my negative feelings’).
The instrument possesses good internal consistency
(α = .90), adequate retest-reliability (r = .75) as well as
sensitivity to change [62]. All subscales have demon-
strated convergent and discriminate validity, including
strong positive correlations with constructs related to
emotion regulation.
Perserverative Thinking Questionnaire (PTQ) PTQ is
a 15-item questionnaire. It was developed to measure re-
petitive negative thinking, [63] which has been found to
be involved in the maintenance of emotional problems,
i.e. anxiety and depression [64]. Participants rate how
they typically think about negative experiences or prob-
lems. Scores range from 0 to 60 and higher scores indicate
more frequent engagement in repetitive negative thinking.
PTQ has shown excellent internal consistency and correl-
ate well with other measure of repetitive negative thinking,
e.g. The Penn State Worry Questionnaire [63].
Beck Depression Inventory-II (BDI) BDI was developed
for quantification of depressive symptoms in patients di-
agnosed with major depression according to DSM-IV
[65]. It has been widely used internationally and corre-
lates well with clinical evaluations and observer ratings
of depression like the Hamilton Depression Rating Scale
[66]. The inventory addresses the patient’s mood and be-
haviour over the previous two weeks. Scores range from
0 to 63; 0-13 indicates minimal depression, 14-19 mild
depression, 20-28 moderate depression, and 29-63 severe
depression [65].
Arnfred et al. BMC Psychiatry  (2017) 17:37 
Page 8 of 14

Work and Social Adjustment Scale (WSAS) Work
and Social Adjustment Scale (WSAS) [67] represents a
simple measurement of impairment of functioning. It
consists of five items, each rated on an 8-point severity
scale adding up to a maximum severity of 40 points. It is
validated for use across the full spectrum of psychiatric
disorders and is used in epidemiological research as well
as clinically [68].
Client Satisfaction Questionnaire (CSQ) CSQ is an
8-item scale loading to one factor of satisfaction with
mental health care service. Responses are 1-4, where 1 is
“very or definitely dissatisfied and 4 is “very or definitely
satisfied.” It does not include a neutral rating [69, 70].
Scoring was originally reported as a sum score 8-32. A
Danish translation has been widely used in the mental
health service, but it has not been validated.
Panic Disorder Severity Scale (PDSS) PDSS is a brief
rating scale with seven items assessing the severity of PD
symptoms and functional impairment. Items are rated
on a 0- to 4-point scale [71, 72].
Liebowitz Social Anxiety Scale - Self-Report (LSAS-SR)
LSAS-SR assesses a range of situations typically feared
by individuals with social anxiety. It has 24 items, di-
vided into subscales of performance anxiety and social
situations. It has acceptable psychometric properties and
the self-report version provides scores close to the ori-
ginal observer rating [73].
Mobility Inventory for Agoraphobia (MIA) MIA as-
sesses agoraphobic avoidance. It consists of 27 items
rated on a 1-5 point scale for avoidance. Each situation
is described with the patient accompanied or alone,
resulting in two different measures of avoidance [74].
Exploratory measures
History and moderating characteristics
Level of Personality Functioning - Brief Form 2.0
(LPFS-BF) LPFS-BF is a brief 12-item self-report inven-
tory developed to assess levels of personality functioning
as defined in the alternative model for personality disorders
in DSM-5 Section III [75–77]. The LPFS-BF measures im-
pairment in personality functioning within the domains of
self-functioning (e.g., Identity and Self-direction) and inter-
personal functioning (e.g., Empathy, Self-esteem, and Intim-
acy). Such features of functioning are considered essential
in adapting to (stressful) life events. [78].
Reflective Functioning Questionnaire (RFQ) RFQ is a
54-item self-report inventory assessing the respondent’s
ability to understand the internal mental states of self
and others. Items are phrased as statements, and the re-
sponse options are 1-6 (from totally disagree to totally
agree). It captures the mentalizing capacity in two do-
mains: Certainty or Uncertainty about mental states,
and low scores are associated with low level personality
function [79, 80].
Personality Inventory for Dsm-5 - Short Form (PID-5
SF) PID-5 SF isan abbreviated 100-item version of the
Personality Inventory for DSM-5 (PID-5) developed to
measure the pathological trait specifiers listed in the al-
ternative model for personality disorders in DSM-5
Section III [76, 81]. The PID-5-SF describes 25 trait
facets organized in five higher-order domains: Negative
Affectivity (vs. Emotional Stability), Detachment (vs.
Extraversion), Antagonism (vs. Aggreableness), Disin-
hibition (vs Conscientiousness), and Psychoticism (vs.
Lucidity). The Danish PID-5-SF has demonstrated sound
psychometric qualities [82, 83]. In the follow-up part of
the present trial, we use composite scores of internalizing
personality features (i.e., Negative Affectivity and Detach-
ment domain scores) derived from the PID-5 SF.
Life Event Checklist for DSM-5 (LEC-5) LEC-5 is a
self-report measure designed to screen for potentially
traumatic events in the patient's lifetime. The LEC-5 as-
sesses exposure to 17 types of events known to poten-
tially result in distress. Response options are “happened
to me”, “witnessed it” “learned about it” “part of my job”
“not sure” and “doesn’t apply”. LEC-5 has demonstrated
adequate psychometric properties as a stand-alone as-
sessment of traumatic exposure [84].
Copenhagen Social Relations Questionnaire (CSRQ)
CSRQ is used for the assessment of the structure and
function of the patient’s social network. It consists of 8
questions pertaining to 5 domains (i.e. parents, friends,
family, children or neighbor’s) and the response options
are ‘always’, ‘often’, ‘sometimes’, ‘seldom’, ‘never’, ‘have none’.
It was developed for and validated in a Danish middle-
aged population [85, 86].
Weekly outcomes – session tracking
Overall Anxiety Severity and Impairment Scale (OASIS)
OASIS is a five-item self-report instrument of severity
of and impairment due to anxiety with established con-
current and discriminant validity. It addresses anxiety
frequency and severity, level of avoidance, work/school/
home interference, and social interference on a five-
point Likert scale [87, 88].
Overall Depression Severity and Impairment Scale
(ODSIS) ODSIS is a five-item self-report measure of
Arnfred et al. BMC Psychiatry  (2017) 17:37 
Page 9 of 14

severity of and impairment due to depression, with
established concurrent and discriminant validity. The
scale addresses depression frequency and severity, level
of engagement, work/school/home interference, and so-
cial interference on a five-point Likert scale [89].
Home-Work Tracker (HWT) HWT is purpose-made
for this study. It is questions concerning patients’ adher-
ence to home-work as well as symptom-coping during
the preceding week.
Session evaluations
Group Questionnaire - Brief 12-Items (GQ12) The
original Group Questionnaire is a 30 item, 0-7 Likert
scale, patient self-rating, session to session questionnaire
with a well-established construct validity, measuring 3
different relational domains in group therapy: positive
bonding, positive working, and negative relationships
[90]. In the current study we will use the recently devel-
oped 12 item Group Questionnaire (Burlingame, personal
communication, 2016).
Evaluation of the course of therapy
A questionnaire focusing on the patient’s evaluation of
the group therapy, which was purpose-made for the
current study, will be distributed at the end of the group
course. Items have been constructed as Likert Scale
feedback forms consisting of a list of statements about
different aspects of the course of group therapy. Re-
sponse possibilities are five categories ranging from very
much in agreement to not at all.
Therapist ratings
Manual adherence checklist A purpose-made self-
evaluation check-list for therapists, designed as a list of
possible interventions will be employed. At the end of
each session, therapists report to which degree they used
each intervention from the list. The results will be ana-
lyzed according to a pre-defined algorithm, defining op-
timal UP and TAU-CBT interventions at different stages
of treatment, and discriminating between allowed and
prohibited interventions. The intervention check-list will
be compared to the external fidelity assessment.
Session setting A fact sheet about session cancellation,
change in therapists, attendance, change of group room
or session length has been developed specifically for the
study.
Statistical considerations
Sample size estimation is based on the primary outcome
measure, WHO-5. In our initial naturalistic study of group
UP, pre-treatment WHO-5 was 34.5 (SD 17.3) and end-of-
treatment 44.8 (SD 17.4) (N = 46) (22). WHO-5 has a
minimum clinical significant difference of 10 (Bech, per-
sonal communication, 2016). For non-inferiority trials, it
is paramount to select a relevant limit for the possible dif-
ference in WHO-5 score that will lead to rejection of the
hypothesis of non-inferiority [91]. We have set the limit to
9, i.e., one point below the minimum clinical significant
difference. Alpha is set to 5% to avoid type I error, result-
ing in a 95% one-sided confidence interval for decision of
non-inferiority. Beta is generally set to 0.1, i.e. a power of
90%. Applying end-point WHO-5 SD of 17,4 and limit of
difference delta: 9 points, if UP-CBT is no less effective
than TAU-CBT, 204 patients are needed (102 in each arm)
to be 90% sure that the lower limit of a 95% one-sided
confidence interval will be above the non-inferiority limit
of - 9. Meeting the risk of drop-outs with an increase of
20% we will include 124 participants in each arm, in total
248 patients.
Main outcomes will be analyzed in an intention-to-
treat (ITT) design, where we will use multiple imputa-
tions to handle missing data. All primary analyses will be
adjusted for the stratification variables (site, diagnosis).
We will use mixed regression analyses that will enable
us to use all outcome ratings and enter separate levels
for groups, therapists and clinical sites. For exploratory
mediator analyses, we will use per-protocol data as well
as ITT and both Autoregressive Cross-Lagged Modeling
and Structural Equation Modeling [92].
Ethics and governance
The trial will be conducted according to national and
international standards of good clinical practice. All par-
ticipants will be provided with written and verbal informa-
tion on the trial so that they can make an informed
decision about their participation. Data will be collected
and handled confidentially in accordance with the rules of
the Danish Data Protection Agency. The protocol has
been approved by the Ethics Committee Region Zealand
(Registration number: 3084871-SJ-582) and the Danish
Data Protection Agency Region Zealand (Registration
number: REG-104-2016). Protocol amendments will
be
communicated at https://clinicaltrials.gov and detailed in
publications. STD-CBT is considered an appropriate and
ethically justified control group, as it is the recommended
treatment for the target group prescribed by the Regional
and National treatment programs in Denmark.
Waiting time to treatment may be slightly increased
due to the project, as the UP-CBT groups reduce the
number of patients available for the STD-CBT groups,
but it is not expected to increase above the limit of the
clinically acceptable.
We monitor for adverse events, in particular suicidal
behavior/ideation. Change of medication or withdrawal
Arnfred et al. BMC Psychiatry  (2017) 17:37 
Page 10 of 14

from the study will be considered in case of increased
suicidal ideation/behavior. First step of change in medi-
cation will, if possible, be dose increase of already insti-
tuted treatment. Next step will be to initiate or cross
over to another type of medication according to a pre-
defined protocol (available on request) established in
accordance with the clinical guidelines in the participating
clinics and the Danish Health Authorities. In case the re-
sponsible psychiatrist considers it necessary to initiate
treatment with hypnotics or anxiolytics, it is possible to do
so, within a limited dose range and according to a prede-
fined protocol (ibid). If it is necessary to institute medical
treatment, not listed in the predefined guidelines, the pa-
tient will continue in group therapy and in the trial, but
the incident will be recorded as an important change of
medicine and as an adverse event.
The first author, SMA, is principal investigator (PI)
and initiated the project. Following a formal collaboration
agreement between the participating regions, Region
Zealand owns the data, and PI has the right to extract
and distribute data to participating researchers. A steer-
ing committee consisting of the heads of the participat-
ing units, ensures the integration of the project with
the day-to-day running of the units, while the scientific
project group consisting of the authors of this protocol,
headed by the PI, is in charge of scientific decisions related
to design, data collection, data analysis and reporting and
conducting the study in line with Good Clinical Practice
guidelines. Signed contracts describe the rights of the in-
volved young researchers as to writing up manuscripts
and authorships. The study does not have a data moni-
toring committee, as allocation is not concealed for
therapists.
Discussion
The current study will be the first RCT investigating the
dissemination of the UP in a MHS setting. Also the
current study will be the first RCT on the UP delivered
in groups. There is a potential risk that the patients in
UP may not be able to recognize their problems in the
symptoms targeted in the group therapy and may, ac-
cordingly, have an increased risk of drop out or of ex-
periencing no effect of the therapy. It is furthermore
possible that being in a group with patients with quite
different symptoms might be experienced as irrelevant
or even overwhelming by the patients. The sensitivity for
these aspects of UP might differ between diagnostic
groups i.e. resulting in patients with SAD perhaps having
less effect of UP, than the other patients. Lack of group
cohesion may ultimately lead to non-attendance and
drop-out of treatment and accordingly to long-term
negative outcome i.e. chronic or recurrent symptoms [93].
Consequently, it is important to have weekly symptom and
attendance tracking. Many of the problems mentioned
may, however, also be seen in STD-CBT. The risk of not
having adequate benefit from STD-CBT is also high as the
number of patients needed to treat for the addition of one
more remitted patient is four, when comparing CBT for
depression with no intervention [94]. These numbers
make the introduction of new treatments highly relevant;
we need to improve CBT beyond what has been estab-
lished as efficient, or to find out how to individualize
treatment strategies.
If our results support the application of UP group
therapy in MHS, we expect that it will be much more
feasible to implement group therapy for depression and
anxiety disorders in smaller clinics, within MHS outside
the main cities and in the primary sector. At this point,
even at the university hospitals, we see quite lengthy
waiting time before group therapy commences. At the
same time, the application of only one manual will sup-
port focused training and supervision, hence increasing
the expertise of therapists. In larger clinics, the use of
UP could also make it possible to compose groups based
on other characteristics than diagnoses i.e. gender, age
or life events. Lastly, the use of UP for those patients,
frequently seen in the MHS, with comorbidity in the
form of two equally important disorders might be par-
ticularly advantageous.
By virtue of the large-scale, randomized design, the
current study will add to the preliminary results of TCBT,
providing information on the efficacy of TCBT compared
to STD-CBT. The explorative moderation and mediation
analyses could spur new hypotheses about mechanisms of
change and the association between treatment effect and
patient characteristics. Future research might focus on
possible improvements of the UP manual, and a particular
focus on those patients who might not benefit from either
UP-CBT or STD-CBT.
Trial status
Training of therapists and outcome assessors is ongoing.
Recruitment commences December 2016 and will con-
tinue until September 2018.
Additional file
Additional file 1: SPIRIT 2013 Checklist: Recommended items to address
in a clinical trial protocol and related documents. (DOC 122 kb)
Abbreviations
CBT: Cognitive Behavior Therapy; MHS: Mental Health Service;
RCT: Randomized Controlled Trial; STD-CBT: Standard CBT i.e. diagnosis
specific manualized CBT; T-CBT: Transdiagnostic CBT; UP: the “Unified
Protocol for Transdiagnostic Treatment of Emotional Disorders” – a specific
manual for transdiagnostic CBT [5, 13]; UP-CBT: The revised Danish group
version of the Unified Protocol for Transdiagnostic Treatment of Emotional
Disorders [22]
Arnfred et al. BMC Psychiatry  (2017) 17:37 
Page 11 of 14

Acknowledgements
The authors sincerely thank Professor David Barlow and his co-workers at
Center for Anxiety and Related Disorders, Boston University, for encouragement
and scientific guidance.
Funding
The project has been funded with 4,5 mill DKK from TRYGfonden (ID114241),
1,75 mill DKK from the Capital Region Mental Health Services (PhD-grant),
0,5 mill DKK from Jascha Foundation, 0,47 mill DKK from Department of
Psychology, Copenhagen University and 0,25 mill DKK from Region Zealand.
Funding bodies have not, and will not, participate in the study design;
collection, management, analysis, and interpretation of data, or writing of
report: They do not have authority over the decision to submit reports for
publication or the conclusions herein.
Availability of data and materials
The datasets generated by the planned study will not be publicly available
due to the rules of the Danish Data Protection Agency, but will be available
from the corresponding author, after publication, on reasonable request and
following signed confidentiality agreement with PI and the Danish Data
Protection Agency Region Zealand.
Study outcomes and supplementary analyses will be submitted for
publication in international and national scientific journal as well as to the
wider public using the Mental Health Service public relation service. Findings
will be presented at scientific and public meetings to potential users, clinicians,
commissioners and treatment providers to support implementations necessary
based on the results.
Authors’ contributions
SMA is principal investigator and manager on the executive level as well as
head academic supervisor. SMA, RA, and NR conceptualized the study with
important contributions from NKR, SP, MA, BB and MH. NR has written the
Danish UP group manual. NKR, RA and NR designed the therapist training
program. SMA was responsible for writing the manuscript with significant
contributions from all other authors. All authors have discussed, reviewed
and approved the manuscript.
Authors’ information
SMA is psychiatrist, clinical research associate professor in psychiatry at
Region Zealand Psychiatry, Slagelse, University of Copenhagen. She has
previously worked as CBT therapist and psychiatrist in different MHS clinics,
but is now full-time researcher.
RA is clinical psychologist, specialist in CBT psychotherapy, and researcher at
Mental Health Center Copenhagen.
MH is a clinical psychologist and researcher at Region Zealand Psychiatry,
Slagelse.
SP is associate professor, PhD, at the Department of Psychology, University of
Copenhagen.
BB is clinical psychologist, PhD and Research Associate at the Psychiatric
Research Unit, Region Zealand, Slagelse.
MA is psychologist, senior researcher, and specialist in CBT currently
employed at the Psychiatric Hospital, Risskov.
NKR is clinical psychologist, and head of Psychotherapy Unit, Mental Health
Center Copenhagen. She is adj. professor University of Aarhus, CBT specialist
and supervisor, and author of several books on CBT and psychotherapy.
NR is clinical psychologist, specialist in CBT psychotherapy, PhD student, at
Mental Health Center Copenhagen.
Competing interests
The authors declare that they have no competing interests.
Consent for publication
Not applicable.
Ethics approval and consent to participate
The protocol was approved by Ethics Committee Region Zealand
(Registration number: 3084871-SJ-582).
All participants will give written informed consent following the National
Danish Ethics Committee’s guidelines, and do so prior to randomization and
intervention allocation. SPIRIT 2013 Checklist: Recommended items to
address in a clinical trial protocol and related documents has been filled out,
and is included as Additional file 1. Protocol version 7.22, 1 Nov 2016, is the
current version, amendments will be addressed at www.clinicaltrials.gov.
Author details
1Psychiatric Hospital Slagelse & Psychiatric Research Unit, Region Zealand
Psychiatry, Faelledvej 6, Building 3, Level 4., DK-4200 Slagelse, Denmark.
2Psychotherapeutic Clinic Nannasgade, Mental Health Centre Copenhagen,
Capital Region Mental Health Services, Copenhagen University Hospital,
Copenhagen, Denmark. 3Department of Psychology, Faculty of Social
Sciences, University of Copenhagen, Copenhagen, Denmark. 4Unit for
Anxiety and Compulsive Disorders, Psychiatric Hospital Risskov, Aarhus
University Hospital, Aarhus, Denmark. 5Institute of Clinical Medicine, Faculty
of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Received: 30 November 2016 Accepted: 23 December 2016
References
1.
Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE.
Lifetime prevalence and age-of-onset distributions of DSM-IV disorders
in the National Comorbidity Survey Replication. Arch Gen Psychiatry.
2005;62(6):593–602.
2.
Brown TA, Campbell LA, Lehman CL, Grisham JR, Mancill RB. Current and
lifetime comorbidity of the DSM-IV anxiety and mood disorders in a large
clinical sample. J Abnorm Psychol. 2001;110(4):585–99.
3.
Goldberg DP, Krueger RF, Andrews G, Hobbs MJ. Emotional disorders:
cluster 4 of the proposed meta-structure for DSM-V and ICD-11. Psychol
Med. 2009;39(12):2043–59.
4.
Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. Prevalence,
severity, and comorbidity of 12-month DSM-IV disorders in the National
Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):617–27.
5.
Barlow DH, Farchione TJ, Fairholme CP, Ellard KK, Boisseau CL, Allen LB,
Ehrenreich-May JT. Unified Protocol for Transdiagnostic Treatment of
Emotional Disorders: Therapist Guide. New York: Oxford University Press; 2011.
6.
Norton PJ. A randomized clinical trial of transdiagnostic cognitve-behavioral
treatments for anxiety disorder by comparison to relaxation training. Behav
Ther. 2012;43(3):506–17.
7.
Barlow DH. Toward a Unified Treatment for Emotional Disorders. Behav
Ther. 2004;35:2005–230.
8.
McEvoy P, Nathan P, Norton P. Efficay of transdiagnostic treatments: A
reveiw of published outcome studes and future research directions. J Cogn
Psychother. 2009;23(1):20–33.
9.
Norton PJ. An open trial of a transdiagnostic cognitive-behavioral group
therapy for anxiety disorder. Behav Ther. 2008;39(3):242–50.
10.
McManus F, Shafran R, Cooper Z. What does a transdiagnostic approach
have to offer the treatment of anxiety disorders? Br J Clin Psychol. 2010;
49(Pt 4):491–505.
11.
Wilamowska ZA, Thompson-Hollands J, Fairholme CP, Ellard KK, Farchione
TJ, Barlow DH. Conceptual background, development, and preliminary data
from the unified protocol for transdiagnostic treatment of emotional
disorders. Depress Anxiety. 2010;27(10):882–90.
12.
Barlow DH. Unified protocol for transdiagnostic treatment of emotional
disorders : therapist guide. New York: Oxford University Press; 2011.
13.
Barlow DH, Ellard KK, Fairholme CP, Farchione TJ, Boisseau CL, Ehrenreich-
May JT. Unified Protocol for Transdiagnostic Treatment of Emotional
Disorders: Work Book. New York: Oxford University Press; 2011.
14.
Norton PJ, Paulus DJ. Toward a Unified Treatment for Emotional Disorders:
Update on the Science and Practice. Behavior Therapy. 2015 in press.
15.
Reinholt N, Krogh J. Efficacy of transdiagnostic cognitive behaviour therapy
for anxiety disorders: a systematic review and meta-analysis of published
outcome studies. Cogn Behav Ther. 2014;43(3):171–84.
16.
Ellard KK, Fairholme CP, Boisseau CL, Farchione TJ, Barlow DH. Unified
Protocol for the Transdiagnostic Treatment of Emotional Disorders: Protocol
Development and Initial outcome data. Cogn Behav Pract. 2010;17:88–101.
17.
Farchione TJ, Fairholme CP, Ellard KK, Boisseau CL, Thompson-Hollands J,
Carl JR, Gallagher MW, Barlow DH. Unified protocol for transdiagnostic
treatment of emotional disorders: a randomized controlled trial. Behav Ther.
2012;43(3):666–78.
18.
Davis L, Barlow DH, Smith L. Comorbidity and the treatment of principal
anxiety disorders in a naturalistic sample. Behav Ther. 2010;41(3):296–305.
Arnfred et al. BMC Psychiatry  (2017) 17:37 
Page 12 of 14

19.
de Ornelas Maia AC, Nardi AE, Cardoso A. The utilization of unified
protocols in behavioral cognitive therapy in transdiagnostic group subjects:
A clinical trial. J Affect Disord. 2015;172:179–83.
20.
Bullis JR, Sauer-Zavala S, Bentley KH, Thompson-Hollands J, Carl JR, Barlow
DH. The unified protocol for transdiagnostic treatment of emotional
disorders: preliminary exploration of effectiveness for group delivery. Behav
Modif. 2015;39(2):295–321.
21.
Sauer-Zavala S, Bentley KH, Wilner JG. Transdiagnostic Treatment of
Borderline Personality Disorder and Comorbid Disorders: A Clinical
Replication Series. J Pers Disord. 2016;30(1):35–51.
22.
Reinholt N, Aharoni R, Winding C, K. RN, Rosenbaum B, Arnfred SM.
Transdiagnostic Group CBT for Anxiety Disorders: The Unified Protocol in
Mental Health Services. Cognitive Behavior Therapy. 2016, in press.
23.
McDermut W, Miller IW, Brown RA. The efficacy of group therapy for
depression: A meta-analysis and review of the empirical research. Clinical
Psychology: Science and Practice. 2001;8(1):98–116.
24.
Digman. Personality Structure: Emergence of the five-factor model. Annu
Rev Psychol. 1990;41(1):417–40.
25.
APA. Diagnostic and Statistical Manual of Mental Disorders. 4th ed.
Washington DC: American Psychiatric Association; 1994.
26.
Brown TA, Chorpita BF, Barlow DH. Structural relationships among dimensions
of the DSM-IV anxiety and mood disorders and dimensions of negative affect,
positive affect, and autonomic arousal. J Abnorm Psychol. 1998;107(2):179–92.
27.
Brown TA. Temporal course and structural relationships among dimensions
of temperament and DSM-IV anxiety and mood disorder constructs. J
Abnorm Psychol. 2007;116(2):313–28.
28.
Carl JR, Gallagher MW, Sauer-Zavala SE, Bentley KH, Barlow DH. A
preliminary investigation of the effects of the unified protocol on
temperament. Compr Psychiatry. 2014;55(6):1426–34.
29.
Sauer-Zavala S, Boswell JF, Gallagher MW, Bentley KH, Ametaj A, Barlow DH.
The role of negative affectivity and negative reactivity to emotions in
predicting outcomes in the unified protocol for the transdiagnostic
treatment of emotional disorders. Behav Res Ther. 2012;50(9):551–7.
30.
Dobson KS, Singer AR. Definitional and Practical Issues in the Assessment of
Treatment Integrety. Clinical Psychology: Science and Practice. 2005;12(4):384–7.
31.
Lambert MJ, Barley DF. Research summary on the therapeutic relationship
and psychotherapy outcome. Psychotherapy: Theory, Research, Practice,
Training. 2001;38(4):357–61.
32.
Kazdin AE. Treatment outcomes, common factors and continued neclect of
mechanisms of change. Clinical Psychology: Science and Practice. 2005;
12(2):184–8.
33.
Zilcha-Mano S, Muran JC, Hungr C, Eubanks CF, Safran JD, Winston A. The
relationship between alliance and outcome: Analysis of a two-person perspective
on alliance and session outcome. J Consult Clin Psychol. 2016;84(6):484–96.
34.
Zilcha-Mano S, Snyder J, Silberschatz G. The effect of congruence in
patient and therapist alliance on patient's symptomatic levels. Psychother
Res. 2016;1–10.
35.
Turk C, Heimberg R, Magee L. Social Anxiety Disorder. In: Barlow DH, editor.
Clinical handbook of psychological disorders. 4th ed. New York: Guilford
Press; 2008. p. 123–63.
36.
Craske MG, Barlow D. Panic Disorder and Agoraphobia. In: Barlow DH,
editor. Clinical handbook of psychological disorders. 4th ed. New York:
Guilford Press; 2008. p. 1–64.
37.
Arendt, Rosenberg. Kognitiv terapi, 1. udgave edn. Kbh.: Hans Reitzel; 2012.
38.
Suhl S, Arpe-Moeller C, Gravesen L. Gruppemanual for panikangst og
agorafobi: 2. og 3. bølge kognitiv adfærdsterapi. 2016.
39.
Due Madsen J. Kognitiv adfærdsterapi ved depression. Virum: Dansk
psykologisk Forlag; 2008.
40.
Lau ME, Calmer J, Bramsen J, Madsen JD. Short-term treatment of
depression. Implementation of group-based cognitive behavioral therapy.
Ugeskr Laeger. 2008;170(15):1246–9.
41.
Scott MJ. Simply effective group cognitive behaviour therapy : a
practitioner's guide. Hove, East Sussex England: Routledge; 2011.
42.
Boswell JF, Gallagher MW, Sauer-Zavala SE, Bullis J, Gorman JM, Shear MK,
Woods S, Barlow DH. Patient characteristics and variability in adherence and
competence in cognitive-behavioral therapy for panic disorder. J Consult
Clin Psychol. 2013;81(3):443–54.
43.
Lowe B, Spitzer RL, Grafe K, Kroenke K, Quenter A, Zipfel S, Buchholz C,
Witte S, Herzog W. Comparative validity of three screening questionnaires
for DSM-IV depressive disorders and physicians' diagnoses. J Affect Disord.
2004;78(2):131–40.
44.
Newnham EA, Hooke GR, Page AC. Monitoring treatment response and
outcomes using the World Health Organization's Wellbeing Index in
psychiatric care. J Affect Disord. 2010;122(1-2):133–8.
45.
Newnham EA, Hooke GR, Page AC. Progress monitoring and feedback in
psychiatric care reduces depressive symptoms. J Affect Disord. 2010;
127(1-3):139–46.
46.
Bech P, Olsen LR, Kjoller M, Rasmussen NK. Measuring well-being rather
than the absence of distress symptoms: a comparison of the SF-36 Mental
Health subscale and the WHO-Five Well-Being Scale. Int J Methods Psychiatr
Res. 2003;12(2):85–91.
47.
Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E,
Hergueta T, Baker R, Dunbar G. The Mini-International Neuropsychiatric
Interview (M.I.N.I.): the development and validation of a structured
diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry.
1998;59 Suppl 20:22–33. quiz 34-57.
48.
Moran P, Leese M, Lee T, Walters P, Thornicroft G, Mann A. Standardised
Assessment of Personality - Abbreviated Scale (SAPAS): preliminary validation
of a brief screen for personality disorder. Br J Psychiatry. 2003;183:228–32.
49.
Hamilton M. The assessment of anxiety states by rating. British Journal of
Medical Psychology. 1959;32:50–5.
50.
Bech P. Dose-response relationship of pregabalin in patients with
generalized anxiety disorder. A pooled analysis of four placebo-controlled
trials. Pharmacol Toxicol. 2007;40(4):163–8.
51.
Meoni P, Salinas E, Brault Y, Hackett D. Pattern of symptom improvement
following treatment with venlafaxine XR in patients with generalized
anxiety disorder. J Clin Psychiatry. 2001;62(11):888–93.
52.
Bech, Psykiatrisk Hospital i Hillerød. Rating scales for affektive lidelser [Rating
scales for Affective Disorders]. Hillerød: Psykiatrisk Forskningsenhed; 2005.
53.
Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry.
1960;23:56–62.
54.
Bech P, Gram LF, Dein E, Jacobsen O, Vitger J, Bolwig TG. Quantitative rating
of depressive states. Acta Psychiatr Scand. 1975;51(3):161–70.
55.
Bech P. Rating scales in depression: limitations and pitfalls. Dialogues Clin
Neurosci. 2006;8(2):207–15.
56.
Derogatis LR, Lipman RS, Rickels K, Uhlenhuth EH, Covi L. The Hopkins
Symptom Checklist (HSCL): a self-report symptom inventory. Behav Sci.
1974;19(1):1–15.
57.
Lipman RS, Covi L, Shapiro AK. The Hopkins Symptom Checklist (HSCL)–
factors derived from the HSCL-90. J Affect Disord. 1979;1(1):9–24.
58.
Müller J, Poster C, Beyer T, Furniss T, Actergarde S. Comparison of Eleven Short
Versions of the Symptom Checklist 90-Revised (SCL-90-R) in the assessment of
general Psychopathology. J Psychopathol Behav Assess. 2010;32:246–54.
59.
Watson D, Clark LA, Tellegen A. Development and validation of brief
measures of positive and negative affect: The PANAS scales. J Pers Soc
Psychol. 1988;54:1063–70.
60.
Krohne HW, Egloff B, Kohlmann CW, Tausch A. Positive and Negative Affect
Schedule (PANAS). Diagnostica. 1996;42:139–56.
61.
Gross JJ, John OP. Individual differences in two emotion regulation
processes: implications for affect, relationships, and well-being. J Pers Soc
Psychol. 2003;85(2):348–62.
62.
Berking M, Wupperman P, Reichardt A, Pejic T, Dippel A, Znoj H. Emotion-
regulation skills as a treatment target in psychotherapy. Behav Res Ther.
2008;46(11):1230–7.
63.
Ehring T, Zetsche U, Weidacker K, Wahl K, Schonfeld S, Ehlers A. The
Perseverative Thinking Questionnaire (PTQ): validation of a content-
independent measure of repetitive negative thinking. J Behav Ther Exp
Psychiatry. 2011;42(2):225–32.
64.
Ehring T, Watkins E. Repetitive Negative Thinking as a Transdiagnostic
Process. Int J Cogn Ther. 2008;1(3):192–205.
65.
Beck AT, Steer RA, Brown GK. Manual for the BDI. San Antonio, Texas: Th
Psychological Corporation; 1996.
66.
Beck AT, Steer RA, Garbin MG. Psychometric Properties of the Beck Depression
Inventory - 25 Years of Evaluation. Clin Psychol Rev. 1988;8(1):77–100.
67.
Mundt JC, Marks IM, Shear MK, Greist JH. The Work and Social Adjustment Scale:
a simple measure of impairment in functioning. Br J Psychiatry. 2002;180:461–4.
68.
Zahra D, Qureshi A, Henley W, Taylor R, Quinn C, Pooler J, Hardy G,
Newbold A, Byng R. The work and social adjustment scale: reliability,
sensitivity and value. Int J Psychiatry Clin Pract. 2014;18(2):131–8.
69.
Attkisson CC, Zwick R. The client satisfaction questionnaire. Psychometric
properties and correlations with service utilization and psychotherapy
outcome. Eval Program Plann. 1982;5(3):233–7.
Arnfred et al. BMC Psychiatry  (2017) 17:37 
Page 13 of 14

70.
Larsen DL, Attkisson CC, Hargreaves WA, Nguyen TD. Assessment of client/
patient satisfaction: development of a general scale. Eval Program Plann.
1979;2(3):197–207.
71.
Shear MK, Brown TA, Barlow DH, Money R, Sholomskas DE, Woods SW,
Gorman JM, Papp LA. Multicenter collaborative panic disorder severity scale.
Am J Psychiatry. 1997;154(11):1571–5.
72.
Bohni MK, Spindler H, Arendt M, Hougaard E, Rosenberg NK. A randomized
study of massed three-week cognitive behavioural therapy schedule for
panic disorder. Acta Psychiatr Scand. 2009;120(3):187–95.
73.
Baker SL, Heinrichs N, Kim HJ, Hofmann SG. The liebowitz social anxiety
scale as a self-report instrument: a preliminary psychometric analysis. Behav
Res Ther. 2002;40(6):701–15.
74.
Chambless DL, Caputo GC, Jasin SE, Gracely EJ, Williams C. The Mobility
Inventory for Agoraphobia. Behav Res Ther. 1985;23(1):35–44.
75.
Bender DS, Morey LC, Skodol AE. Toward a model for assessing level of
personality functioning in DSM-5, part I: a review of theory and methods. J
Pers Assess. 2011;93(4):332–46.
76.
Association AP. Diagnostic and Statistical Manual of Mental Disorders
(DSM-5\FFFD). 5th ed. Washington: American Psychiatric Publishing; 2013.
77.
Hutsebaut J, Feenstra DJ, Kamphuis JH. Development and Preliminary
Psychometric Evaluation of a Brief Self-Report Questionnaire for the
Assessment of the DSM-5 level of Personality Functioning Scale: The LPFS
Brief Form (LPFS-BF). Personal Disord. 2016;7(2):192–7.
78.
Hopwood CJ. Personality traits in the DSM-5. J Pers Assess. 2011;93(4):398–405.
79.
Fonagy P, Luyten P, Moulton-Perkins A, Lee Y-W, Warren F, Howard S,
Ghinai R, Fearon P, Lowyck B. Development and Validation of a Self-Report
Measure of Mentalizing: The Reflective Functioning Questionairre. PLoS One.
2016;11(7):1–28.
80.
Ha C, Sharp C, Ensink K, Fonagy P, Cirino P. The measurement of reflective
function in adolescents with and without borderline traits. J Adolesc. 2013;
36(6):1215–23.
81.
Krueger RF, Derringer J, Markon KE, Watson D, Skodol AE. Initial construction
of a maladaptive personality trait model and inventory for DSM-5. Psychol
Med. 2012;42(9):1879–90.
82.
Bach B, Maples-Keller JL, Bo S, Simonsen E. The alternative DSM-5
personality disorder traits criterion: A comparative examination of three self-
report forms in a Danish population. Personal Disord. 2016;7(2):124–35.
83.
Bo S, Bach B, Mortensen EL, Simonsen E. Reliability and Hierarchical
Structure of DSM-5 Pathological Traits in a Danish Mixed Sample. J Pers
Disord. 2016;30(1):112–29.
84.
Gray MJ, Litz BT, Hsu JL, Lombardo TW. Psychometric properties of the life
events checklist. Assessment. 2004;11(4):330–41.
85.
Lund R, Christensen U, Nilsson CJ, Kriegbaum M, Hulvej Rod N. Stressful
social relations and mortality: a prospective cohort study. J Epidemiol
Community Health. 2014;68(8):720–7.
86.
Lund R, Nielsen LS, Henriksen PW, Schmidt L, Avlund K, Christensen U.
Content validity and reliability of the Copenhagen social relations
questionnaire. J Aging Health. 2014;26(1):128–50.
87.
Norman SB, Allard CB, Trim RS, Thorp SR, Behrooznia M, Masino TT, Stein
MB. Psychometrics of the Overall Anxiety Severity and Impairment Scale
(OASIS) in a sample of women with and without trauma histories. Arch
Womens Ment Health. 2013;16(2):123–9.
88.
Norman SB, Cissell SH, Means-Christensen AJ, Stein MB. Development and
validation of an Overall Anxiety Severity And Impairment Scale (OASIS).
Depress Anxiety. 2006;23(4):245–9.
89.
Bentley KH, Gallagher MW, Carl JR, Barlow DH. Development and validation
of the Overall Depression Severity and Impairment Scale. Psychol Assess.
2014;26(3):815–30.
90.
Krogel J, Burlingame G, Chapman C, Renshaw T, Gleave R, Beecher M,
Macnair-Semands R. The Group Questionnaire: a clinical and empirically
derived measure of group relationship. Psychother Res. 2013;23(3):344–54.
91.
Jones B, Jarvis P, Lewis JA, Ebbutt AF. Trials to assess equivalence: the
importance of rigorous methods. BMJ. 1996;313(7048):36–9.
92.
Kazdin AE. Mediators and mechanisms of change in psychotherapy
research. Annu Rev Clin Psychol. 2007;3:1–27.
93.
Durham RC, Chambers JA, Power KG, Sharp DM, Macdonald RR, Major KA,
Dow MG, Gumley AI. Long-term outcome of cognitive behaviour therapy
clinical trials in central Scotland. Health Technol Assess. 2005;9(42):1–174.
94.
Jakobsen JC, Hansen JL, Storebo OJ, Simonsen E, Gluud C. The effects of
cognitive therapy versus 'no intervention' for major depressive disorder.
PLoS One. 2011;6(12):e28299.
•  We accept pre-submission inquiries 
•  Our selector tool helps you to ﬁnd the most relevant journal
•  We provide round the clock customer support 
•  Convenient online submission
•  Thorough peer review
•  Inclusion in PubMed and all major indexing services 
•  Maximum visibility for your research
Submit your manuscript at
www.biomedcentral.com/submit
Submit your next manuscript to BioMed Central 
and we will help you at every step:
Arnfred et al. BMC Psychiatry  (2017) 17:37 
Page 14 of 14