Introduction: The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) delivered in a group format could facilitate the implementation of evidence-based psychological treatments. Objective: This study compared the efficacy of group UP and diagnosis-specific cognitive behavioral therapy (dCBT) for anxiety and depression in outpatient mental health services. Methods: In this pragmatic, multi-center, single-blinded, non-inferiority, randomized controlled trial (RCT), we assigned 291 patients with major depressive disorder, social anxiety disorder, panic disorder, or agoraphobia to 14 weekly sessions in mixed-diagnosis UP or single-diagnosis dCBT groups. The primary test was non-inferiority, using a priori criteria, on the World Health Organisation 5 Well-Being Index (WHO-5) at the end of the treatment. Secondary outcomes were functioning and symptoms. We assessed outcomes at baseline, end-of-treatment, and at a 6-month follow-up. A modified per-protocol analysis was performed. Results: At end-of-treatment, WHO-5 mean scores for patients in UP (n = 148) were non-inferior to those of patients in dCBT (n = 143; mean difference –2.94; 95% CI –8.10 to 2.21). Results were inconclusive for the WHO-5 at the 6-month follow-up. Results for secondary outcomes were non-inferior at end-of-treatment and the 6-month follow-up. Client satisfaction and rates of attrition, response, remission, and deterioration were similar across conditions. Conclusions: This RCT demonstrated non-inferior acute-phase outcomes of group-delivered UP compared with dCBT for major depressive disorder, social anxiety disorder, panic disorder, and agoraphobia in outpatient mental health services. The long-term effects of UP on well-being need further investigation. If study findings are replicated, UP should be considered a viable alternative to dCBT for common anxiety disorders and depression in outpatient mental health services.

1.
Whiteford
HA
,
Degenhardt
L
,
Rehm
J
,
Baxter
AJ
,
Ferrari
AJ
,
Erskine
HE
, et al
Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010
.
Lancet
.
2013
Nov
;
382
(
9904
):
1575
86
.
[PubMed]
0140-6736
2.
Baxter
AJ
,
Scott
KM
,
Vos
T
,
Whiteford
HA
.
Global prevalence of anxiety disorders: a systematic review and meta-regression
.
Psychol Med
.
2013
May
;
43
(
5
):
897
910
.
[PubMed]
0033-2917
3.
Ferrari
AJ
,
Somerville
AJ
,
Baxter
AJ
,
Norman
R
,
Patten
SB
,
Vos
T
, et al
Global variation in the prevalence and incidence of major depressive disorder: a systematic review of the epidemiological literature
.
Psychol Med
.
2013
Mar
;
43
(
3
):
471
81
.
[PubMed]
0033-2917
4.
Hendriks
SM
,
Spijker
J
,
Licht
CM
,
Hardeveld
F
,
de Graaf
R
,
Batelaan
NM
, et al
Long-term disability in anxiety disorders
.
BMC Psychiatry
.
2016
Jul
;
16
(
1
):
248
.
[PubMed]
1471-244X
5.
Comer
JS
,
Blanco
C
,
Hasin
DS
,
Liu
SM
,
Grant
BF
,
Turner
JB
, et al
Health-related quality of life across the anxiety disorders: results from the national epidemiologic survey on alcohol and related conditions (NESARC)
.
J Clin Psychiatry
.
2011
Jan
;
72
(
1
):
43
50
.
[PubMed]
0160-6689
6.
Gustavsson
A
,
Svensson
M
,
Jacobi
F
,
Allgulander
C
,
Alonso
J
,
Beghi
E
, et al;
CDBE2010Study Group
.
Cost of disorders of the brain in Europe 2010
.
Eur Neuropsychopharmacol
.
2011
Oct
;
21
(
10
):
718
79
.
[PubMed]
0924-977X
7.
National Institute for Health and Clinical Excellence (NICE)
.
Social anxiety disorder: recognition, assessment and treatment
.
British Psychological Society and Royal College of Psychiatrists
;
2013
.
8.
National Institute for Health and Clinical Excellence (NICE)
.
Depression: the treatment and management of depression in adults (CG90 updated edition)
.
British Psychological Society and Royal College of Psychiatrists
;
2010
.
9.
National Institute for Health and Clinical Excellence (NICE)
.
Generalised anxiety disorder and panic disorder in adults: management. NICE guidelines
[
CG113
]
British Psychological Society and Royal College of Psychiatrists
;
2011
.
10.
Alonso
J
,
Liu
Z
,
Evans-Lacko
S
,
Sadikova
E
,
Sampson
N
,
Chatterji
S
, et al;
WHO World Mental Health Survey Collaborators
.
Treatment gap for anxiety disorders is global: Results of the World Mental Health Surveys in 21 countries
.
Depress Anxiety
.
2018
Mar
;
35
(
3
):
195
208
.
[PubMed]
1091-4269
11.
McHugh
RK
,
Barlow
DH
.
The dissemination and implementation of evidence-based psychological treatments. A review of current efforts
.
Am Psychol
.
2010
Feb-Mar
;
65
(
2
):
73
84
.
[PubMed]
0003-066X
12.
Barlow
DH
,
Allen
LB
,
Choate
ML
.
Toward a unified treatment for emotional disorders
.
Behav Ther
.
2004
Nov
;
35
(
2
):
205
30
.
[PubMed]
0005-7894
13.
McEvoy
PM
,
Nathan
P
,
Norton
PJ
.
Efficacy of transdiagnostic treatments: A review of published outcome studies and future research directions
.
J Cogn Psychother
.
2009
;
23
(
1
):
20
33
. 0889-8391
14.
Newby
JM
,
Twomey
C
,
Yuan Li
SS
,
Andrews
G
.
Transdiagnostic computerised cognitive behavioural therapy for depression and anxiety: A systematic review and meta-analysis
.
J Affect Disord
.
2016
Jul
;
199
:
30
41
.
[PubMed]
0165-0327
15.
Pearl
SB
,
Norton
PJ
.
Transdiagnostic versus diagnosis specific cognitive behavioural therapies for anxiety: A meta-analysis
.
J Anxiety Disord
.
2017
Mar
;
46
:
11
24
.
[PubMed]
0887-6185
16.
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
.
[PubMed]
1650-6073
17.
Barlow
DH
,
Farchione
TJ
,
Fairholme
CP
,
Ellard
KK
,
Boisseau
CL
,
Allen
LB
, et al
Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Therapist Guide
.
New York
:
Oxford University Press
;
2011
.
18.
Barlow
DH
,
Sauer-Zavala
S
,
Carl
JR
,
Bullis
JR
,
Ellard
KK
.
The nature, diagnosis, and treatment of neuroticism back to the future
.
Clin Psychol Sci
.
2014
;
2
(
3
):
344
65
. 2167-7026
19.
Cuijpers
P
,
Smit
F
,
Penninx
BW
,
de Graaf
R
,
ten Have
M
,
Beekman
AT
.
Economic costs of neuroticism: a population-based study
.
Arch Gen Psychiatry
.
2010
Oct
;
67
(
10
):
1086
93
.
[PubMed]
0003-990X
20.
Sakiris
N
,
Berle
D
.
A systematic review and meta-analysis of the Unified Protocol as a transdiagnostic emotion regulation based intervention
.
Clin Psychol Rev
.
2019
Aug
;
72
:
101751
.
[PubMed]
0272-7358
21.
Cassiello-Robbins
C
,
Southward
MW
,
Tirpak
JW
,
Sauer-Zavala
S
.
A systematic review of Unified Protocol applications with adult populations: facilitating widespread dissemination via adaptability
.
Clin Psychol Rev
.
2020
Jun
;
78
:
101852
.
[PubMed]
0272-7358
22.
Barlow
DH
,
Farchione
TJ
,
Bullis
JR
,
Gallagher
MW
,
Murray-Latin
H
,
Sauer-Zavala
S
, et al
The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders Compared With Diagnosis-Specific Protocols for Anxiety Disorders: A Randomized Clinical Trial
.
JAMA Psychiatry
.
2017
Sep
;
74
(
9
):
875
84
.
[PubMed]
2168-622X
23.
Ross
EL
,
Vijan
S
,
Miller
EM
,
Valenstein
M
,
Zivin
K
.
The Cost-Effectiveness of Cognitive Behavioral Therapy Versus Second-Generation Antidepressants for Initial Treatment of Major Depressive Disorder in the United States: A Decision Analytic Model
.
Ann Intern Med
.
2019
Dec
;
171
(
11
):
785
95
.
[PubMed]
0003-4819
24.
Norton
PJ
,
Roberge
P
.
Transdiagnostic Therapy
.
Psychiatr Clin North Am
.
2017
Dec
;
40
(
4
):
675
87
.
[PubMed]
0193-953X
25.
Arnfred
SM
,
Aharoni
R
,
Hvenegaard
M
,
Poulsen
S
,
Bach
B
,
Arendt
M
, et al
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
.
BMC Psychiatry
.
2017
Jan
;
17
(
1
):
37
.
[PubMed]
1471-244X
26.
Boutron
I
,
Moher
D
,
Altman
DG
,
Schulz
KF
,
Ravaud
P
,
Group
C
;
CONSORT Group
.
Extending the CONSORT statement to randomized trials of nonpharmacologic treatment: explanation and elaboration
.
Ann Intern Med
.
2008
Feb
;
148
(
4
):
295
309
.
[PubMed]
0003-4819
27.
Piaggio
G
,
Elbourne
DR
,
Pocock
SJ
,
Evans
SJ
,
Altman
DG
,
Group
C
;
CONSORT Group
.
Reporting of noninferiority and equivalence randomized trials: extension of the CONSORT 2010 statement
.
JAMA
.
2012
Dec
;
308
(
24
):
2594
604
.
[PubMed]
0098-7484
28.
American Psychiatric Association (APA)
.
Diagnostic and Statistical Manual of Mental Disorders (DSM-5). 5
.
Washington
:
American Psychiatric Publishing
;
2013
.
29.
Turk
C
,
Heimberg
R
,
Magee
L
. Social Anxiety Disorder. In: Barlow DH, editor. Clinical handbook of psychological disorders. 4. ed. New York: Guilford Press;
2008
. p. 123-63.
30.
Craske
MG
,
Barlow
D
. Panic Disorder and Agoraphobia. In: Barlow DH, editor. Clinical handbook of psychological disorders. 4. ed. New York: Guilford Press;
2008
. p. 1-64.
31.
Due Madsen
J.
Kognitiv adfærdsterapi ved depression [Cognitive behavioural therapy for depression]. Virum: Dansk psykologisk Forlag;
2008
.
32.
Young
J
,
Beck
AT
.
Cognitive Therapy Scale.
Rating Manual (unpublished). Philadelphia: University of Pennsylvania;
1980
.
33.
Topp
CW
,
Østergaard
SD
,
Søndergaard
S
,
Bech
P
.
The WHO-5 Well-Being Index: a systematic review of the literature
.
Psychother Psychosom
.
2015
;
84
(
3
):
167
76
.
[PubMed]
0033-3190
34.
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
May
;
180
(
5
):
461
4
.
[PubMed]
0007-1250
35.
Olsen
LR
,
Mortensen
EL
,
Bech
P
.
The SCL-90 and SCL-90R versions validated by item response models in a Danish community sample
.
Acta Psychiatr Scand
.
2004
Sep
;
110
(
3
):
225
9
.
[PubMed]
0001-690X
36.
Bech
P
.
Rating scales for affective disorders: their validity and consistency
.
Acta Psychiatr Scand Suppl
.
1981
;
295
:
1
101
.
[PubMed]
0065-1591
37.
Carrozzino
D
,
Patierno
C
,
Fava
GA
,
Guidi
J
.
The Hamilton Rating Scales for Depression: A Critical Review of Clinimetric Properties of Different Versions
.
Psychother Psychosom
.
2020
;
89
(
3
):
133
50
.
[PubMed]
0033-3190
38.
Beck
AT
,
Steer
RA
,
Brown
GK
.
Beck Depression Inventory Manual
. 2nd ed.
San Antonio (Texas)
:
Psychological Corporation
;
1996
.
39.
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
Jun
;
40
(
6
):
701
15
.
[PubMed]
0005-7967
40.
Chambless
DL
,
Caputo
GC
,
Jasin
SE
,
Gracely
EJ
,
Williams
C
.
The Mobility Inventory for Agoraphobia
.
Behav Res Ther
.
1985
;
23
(
1
):
35
44
.
[PubMed]
0005-7967
41.
Shear
MK
,
Brown
TA
,
Barlow
DH
,
Money
R
,
Sholomskas
DE
,
Woods
SW
, et al
Multicenter collaborative panic disorder severity scale
.
Am J Psychiatry
.
1997
Nov
;
154
(
11
):
1571
5
.
[PubMed]
0002-953X
42.
Christensen
SM
.
M. Evaluering af SATSpulje-projektet: Lær at tackle angst og depression
[
Evaluating the ’New beginnings for patients with anxiety and depression, a Danish lay person guided self-help program’
]
København
:
Sundhedsstyrelsen
;
2016
.
43.
Sheehan
DV
,
Lecrubier
Y
,
Sheehan
KH
,
Amorim
P
,
Janavs
J
,
Weiller
E
, et al
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
.
[PubMed]
0160-6689
44.
McGraw
KO
,
Wong
SP
.
Forming inferences about some intraclass correlation coefficients
.
Psychol Methods
.
1996
;
1
(
1
):
30
46
. 1082-989X
45.
Koo
TK
,
Li
MY
.
A Guideline of Selecting and Reporting Intraclass Correlation Coefficients for Reliability Research
.
J Chiropr Med
.
2016
Jun
;
15
(
2
):
155
63
.
[PubMed]
1556-3707
46.
IBMCorp
. IBM SPSS Statistics for Windows. In: IBMCorp., editor. Armonk, NY: IBM Corp.;
2017
.
47.
StataCorp
.
Stata Statistical Software: Release 15
.
College Station (TX)
:
StataCorp LLC
;
2017
.
48.
Julious
SA
.
Sample sizes for clinical trials with normal data
.
Stat Med
.
2004
Jun
;
23
(
12
):
1921
86
.
[PubMed]
0277-6715
49.
Matilde Sanchez
M
,
Chen
X
.
Choosing the analysis population in non-inferiority studies: per protocol or intent-to-treat
.
Stat Med
.
2006
Apr
;
25
(
7
):
1169
81
.
[PubMed]
0277-6715
50.
Cohen
J
.
Statistical power analysis for the behavioral sciences
.
New York (NY)
:
Routledge Academic
;
1988
.
51.
Guidi
J
,
Brakemeier
EL
,
Bockting
CL
,
Cosci
F
,
Cuijpers
P
,
Jarrett
RB
, et al
Methodological Recommendations for Trials of Psychological Interventions
.
Psychother Psychosom
.
2018
;
87
(
5
):
276
84
.
[PubMed]
0033-3190
52.
Amick
HR
,
Gartlehner
G
,
Gaynes
BN
,
Forneris
C
,
Asher
GN
,
Morgan
LC
, et al
Comparative benefits and harms of second generation antidepressants and cognitive behavioral therapies in initial treatment of major depressive disorder: systematic review and meta-analysis
.
BMJ
.
2015
Dec
;
351
:
h6019
.
[PubMed]
0959-8138
53.
Springer
KS
,
Levy
HC
,
Tolin
DF
.
Remission in CBT for adult anxiety disorders: A meta-analysis
.
Clin Psychol Rev
.
2018
Apr
;
61
:
1
8
.
[PubMed]
0272-7358
54.
Rubin
A
,
Yu
M
.
Within-group effect size benchmarks for cognitive–behavioral therapy in the treatment of adult depression
.
Soc Work Res
.
2017
;
41
(
3
):
135
44
. 1070-5309
55.
Bandelow
B
,
Sagebiel
A
,
Belz
M
,
Görlich
Y
,
Michaelis
S
,
Wedekind
D
.
Enduring effects of psychological treatments for anxiety disorders: meta-analysis of follow-up studies
.
Br J Psychiatry
.
2018
Jun
;
212
(
6
):
333
8
.
[PubMed]
0007-1250
56.
Wiles
N
,
Thomas
L
,
Abel
A
,
Ridgway
N
,
Turner
N
,
Campbell
J
, et al
Cognitive behavioural therapy as an adjunct to pharmacotherapy for primary care based patients with treatment resistant depression: results of the CoBalT randomised controlled trial
.
Lancet
.
2013
Feb
;
381
(
9864
):
375
84
.
[PubMed]
0140-6736
57.
Osma
JC
,
Crespo
E
,
Garcia-Palacios
A
.
The unified protocol for transdiagnostic treatment of emotional disorders in group format in a spanish public mental health setting
.
Behav Psychology.
2015
;
23
(
3
):
447
66
.
58.
Cuijpers
P
,
Van Straten
A
,
Warmerdam
L
.
Are individual and group treatments equally effective in the treatment of depression in adults? A meta-analysis
.
Eur J Psychiatry
.
2008
;
22
(
1
):
38
51
. 0213-6163
59.
Cuijpers
P
,
Reijnders
M
,
Karyotaki
E
,
de Wit
L
,
Ebert
DD
.
Negative effects of psychotherapies for adult depression: A meta-analysis of deterioration rates
.
J Affect Disord
.
2018
Oct
;
239
:
138
45
.
[PubMed]
0165-0327
60.
van Dis
EA
,
van Veen
SC
,
Hagenaars
MA
,
Batelaan
NM
,
Bockting
CL
,
van den Heuvel
RM
, et al
Long-term Outcomes of Cognitive Behavioral Therapy for Anxiety-Related Disorders: A Systematic Review and Meta-analysis
.
JAMA Psychiatry
.
2020
Mar
;
77
(
3
):
265
73
.
[PubMed]
2168-622X
61.
Kazantzis
N
,
Brownfield
NR
,
Mosely
L
,
Usatoff
AS
,
Flighty
AJ
.
Homework in Cognitive Behavioral Therapy: A Systematic Review of Adherence Assessment in Anxiety and Depression (2011-2016)
.
Psychiatr Clin North Am
.
2017
Dec
;
40
(
4
):
625
39
.
[PubMed]
0193-953X
62.
Fava
GA
,
Guidi
J
.
The pursuit of euthymia
.
World Psychiatry
.
2020
Feb
;
19
(
1
):
40
50
.
[PubMed]
1723-8617
63.
Guidi
J
,
Fava
GA
.
The emerging role of euthymia in psychotherapy research and practice
.
Clin Psychol Rev
.
2020
Dec
;
82
:
101941
.
[PubMed]
0272-7358
64.
Hasler
G
.
Well-Being: An Important Concept for Psychotherapy and Psychiatric Neuroscience
.
Psychother Psychosom
.
2016
;
85
(
5
):
255
61
.
[PubMed]
0033-3190
65.
Eskildsen
A
,
Reinholt
N
,
van Bronswijk
S
,
Brund
RB
,
Christensen
AB
,
Hvenegaard
M
, et al
Personalized Psychotherapy for Outpatients with Major Depression and Anxiety Disorders: Transdiagnostic Versus Diagnosis-Specific Group Cognitive Behavioural Therapy
.
Cognit Ther Res
.
2020
;
44
(
5
):
988
1001
. 0147-5916
66.
Committee for Medicinal Products for Human Use
Efficacy Working Party
Committee for Release for Consultation
.
Committee for Medicinal Products for Human Use (CHMP) guideline on the choice of the non-inferiority margin
.
Stat Med
.
2006
May
;
25
(
10
):
1628
38
.
[PubMed]
0277-6715
67.
Fava
GA
,
Cosci
F
,
Offidani
E
,
Guidi
J
.
Behavioral Toxicity Revisited: Iatrogenic Comorbidity in Psychiatric Evaluation and Treatment
.
J Clin Psychopharmacol
.
2016
Dec
;
36
(
6
):
550
3
.
[PubMed]
0271-0749
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