Introduction: Persistent medically unexplained symptoms (MUS) are a major burden for health care. Cognitive behaviour therapy (CBT) is efficacious for patients with MUS, with small to medium effects. The current study investigates whether therapy outcomes of a CBT for MUS patients can be improved by complementing it with emotion regulation training. Methods: In a multicentre trial 255 patients with at least three persisting MUS were randomised to 20 sessions of either conventional CBT (n = 128) or CBT complemented with emotion regulation training (ENCERT; n = 127). Somatic symptom severity and secondary outcomes were assessed at pre-treatment, therapy session 8, end of therapy, and 6-month follow-up. Results: Linear mixed-effect models revealed medium to large effects in both study arms for almost all outcomes at the end of therapy and 6-month follow-up. ENCERT and CBT did not differ in their effect on the primary outcome (d = 0.20, 95% CI: –0.04 to 0.44). Significant time × group cross-level interactions suggested ENCERT to be of more benefit than conventional CBT for a few secondary outcomes. Moderator analyses revealed higher effects of ENCERT in patients with co-morbid mental disorders. Discussion/Conclusions: Current findings are based on a representative sample. Results demonstrate that both CBT and ENCERT can achieve strong effects on primary and secondary outcomes in MUS patients. Our results do not indicate that adding a training in emotion regulation skills generally improves the effect of CBT across all patients with MUS. Large effect sizes of both treatments and potential specific benefits of ENCERT for patients with co-morbid mental disorders are discussed.

1.
Sharpe
M
,
Mayou
R
,
Bass
C
. Concepts, theories and terminology. In:
Mayou
R
,
Bass
C
,
Sharpe
M
, editors
.
Treatment of functional somatic symptoms
.
Oxford, UK
:
Oxford University Press
;
1995
. pp.
3
16
.
2.
American Psychiatric Association
.
Diagnostic and statistical manual for mental disorders
. Fourth edition, text revision.
Washington (DC)
:
American Psychiatric Press
;
2000
.
3.
American Psychiatric Association
.
Diagnostic and statistical manual of mental disorders.
Fifth edition. DSM-5. Washington, DC: APA;
2013
.
4.
Budtz-Lilly
A
,
Schröder
A
,
Rask
MT
,
Fink
P
,
Vestergaard
M
,
Rosendal
M
.
Bodily distress syndrome: A new diagnosis for functional disorders in primary care?
BMC Fam Pract
.
2015
Dec
;
16
(
1
):
180
.
[PubMed]
1471-2296
5.
Longstreth
GF
,
Thompson
WG
,
Chey
WD
,
Houghton
LA
,
Mearin
F
,
Spiller
RC
.
Functional bowel disorders
.
Gastroenterology
.
2006
Apr
;
130
(
5
):
1480
91
.
[PubMed]
0016-5085
6.
Fukuda
K
,
Straus
SE
,
Hickie
I
,
Sharpe
MC
,
Dobbins
JG
,
Komaroff
A
;
International Chronic Fatigue Syndrome Study Group
.
The chronic fatigue syndrome: a comprehensive approach to its definition and study
.
Ann Intern Med
.
1994
Dec
;
121
(
12
):
953
9
.
[PubMed]
0003-4819
7.
Wolfe
F
,
Clauw
DJ
,
Fitzcharles
MA
,
Goldenberg
DL
,
Häuser
W
,
Katz
RS
, et al
Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia
.
J Rheumatol
.
2011
Jun
;
38
(
6
):
1113
22
.
[PubMed]
0315-162X
8.
de Waal
MW
,
Arnold
IA
,
Eekhof
JA
,
van Hemert
AM
.
Somatoform disorders in general practice: prevalence, functional impairment and comorbidity with anxiety and depressive disorders
.
Br J Psychiatry
.
2004
Jun
;
184
(
6
):
470
6
.
[PubMed]
0007-1250
9.
Rask
MT
,
Rosendal
M
,
Fenger-Grøn
M
,
Bro
F
,
Ørnbøl
E
,
Fink
P
.
Sick leave and work disability in primary care patients with recent-onset multiple medically unexplained symptoms and persistent somatoform disorders: a 10-year follow-up of the FIP study
.
Gen Hosp Psychiatry
.
2015
Jan-Feb
;
37
(
1
):
53
9
.
[PubMed]
0163-8343
10.
Henningsen
P
,
Zipfel
S
,
Sattel
H
,
Creed
F
.
Management of functional somatic syndromes and bodily distress
.
Psychother Psychosom
.
2018
;
87
(
1
):
12
31
.
[PubMed]
0033-3190
11.
Van Dessel
N
,
Den Boeft
M
,
Van der Wouden
JC
,
Kleinstäuber
M
,
Leone
SS
,
Terluin
B
, et al
Non-pharmacological interventions for somatoform disorders and medically unexplained physical symptoms (MUPS) in adults. Cochrane Database Syst Rev 2014; Issue 11 Art No: CD011142 http://dxdoiorg/101002/14651858CD011142pub2.
2014
.
12.
Bogaerts
K
,
Janssens
T
,
De Peuter
S
,
Van Diest
I
,
Van den Bergh
O
.
Negative affective pictures can elicit physical symptoms in high habitual symptom reporters
.
Psychol Health
.
2010
Jul
;
25
(
6
):
685
98
.
[PubMed]
0887-0446
13.
van Eck van der Sluijs
J
,
Ten Have
M
,
Rijnders
C
,
van Marwijk
H
,
de Graaf
R
,
van der Feltz-Cornelis
C
.
Medically unexplained and explained physical symptoms in the general population: association with prevalent and incident mental disorders
.
PLoS One
.
2015
Apr
;
10
(
4
):
e0123274
.
[PubMed]
1932-6203
14.
Löwe
B
,
Spitzer
RL
,
Williams
JB
,
Mussell
M
,
Schellberg
D
,
Kroenke
K
.
Depression, anxiety and somatization in primary care: syndrome overlap and functional impairment
.
Gen Hosp Psychiatry
.
2008
May-Jun
;
30
(
3
):
191
9
.
[PubMed]
0163-8343
15.
Deary
IJ
,
Scott
S
,
Wilson
JA
.
Neuroticism, alexithymia and medically unexplained symptoms
.
Pers Individ Dif
.
1997
;
22
(
4
):
551
64
. 0191-8869
16.
De Gucht
V
,
Heiser
W
.
Alexithymia and somatisation: quantitative review of the literature
.
J Psychosom Res
.
2003
May
;
54
(
5
):
425
34
.
[PubMed]
0022-3999
17.
Schwarz
J
,
Rief
W
,
Radkovsky
A
,
Berking
M
,
Kleinstäuber
M
.
Negative affect as mediator between emotion regulation and medically unexplained symptoms
.
J Psychosom Res
.
2017
Oct
;
101
:
114
21
.
[PubMed]
0022-3999
18.
Koechlin
H
,
Coakley
R
,
Schechter
N
,
Werner
C
,
Kossowsky
J
.
The role of emotion regulation in chronic pain: A systematic literature review
.
J Psychosom Res
.
2018
Apr
;
107
:
38
45
.
[PubMed]
0022-3999
19.
Kohl
A
,
Rief
W
,
Glombiewski
JA
.
Do fibromyalgia patients benefit from cognitive restructuring and acceptance? An experimental study
.
J Behav Ther Exp Psychiatry
.
2014
Dec
;
45
(
4
):
467
74
.
[PubMed]
0005-7916
20.
Vowles
KE
,
McNeil
DW
,
Gross
RT
,
McDaniel
ML
,
Mouse
A
,
Bates
M
, et al
Effects of pain acceptance and pain control strategies on physical impairment in individuals with chronic low back pain
.
Behav Ther
.
2007
Dec
;
38
(
4
):
412
25
.
[PubMed]
0005-7894
21.
Kleinstäuber
M
,
Gottschalk
J
,
Ruckmann
J
,
Probst
T
,
Rief
W
.
Acceptance and cognitive reappraisal as regulation strategies of symptom annoyance in patients with medically unexplained physical symptoms
.
Cognit Ther Res
.
2019
;
43
(
3
):
570
84
. 0147-5916
22.
Sloan
E
,
Hall
K
,
Moulding
R
,
Bryce
S
,
Mildred
H
,
Staiger
PK
.
Emotion regulation as a transdiagnostic treatment construct across anxiety, depression, substance, eating and borderline personality disorders: A systematic review
.
Clin Psychol Rev
.
2017
Nov
;
57
:
141
63
.
[PubMed]
0272-7358
23.
Allen
LA
,
Woolfolk
RL
,
Escobar
JI
,
Gara
MA
,
Hamer
RM
.
Cognitive-behavioral therapy for somatization disorder: a randomized controlled trial
.
Arch Intern Med
.
2006
Jul
;
166
(
14
):
1512
8
.
[PubMed]
0003-9926
24.
Lumley
MA
,
Schubiner
H
,
Lockhart
NA
,
Kidwell
KM
,
Harte
SE
,
Clauw
DJ
, et al
Emotional awareness and expression therapy, cognitive behavioral therapy, and education for fibromyalgia: a cluster-randomized controlled trial
.
Pain
.
2017
Dec
;
158
(
12
):
2354
63
.
[PubMed]
0304-3959
25.
Thakur
ER
,
Holmes
HJ
,
Lockhart
NA
,
Carty
JN
,
Ziadni
MS
,
Doherty
HK
, et al
Emotional awareness and expression training improves irritable bowel syndrome: A randomized controlled trial
.
Neurogastroenterol Motil
.
2017
Dec
;
29
(
12
):
e13143
.
[PubMed]
1350-1925
26.
Chavooshi
B
,
Mohammadkhani
P
,
Dolatshahi
B
.
A randomized double-blind controlled trial comparing davanloo intensive short-term dynamic psychotherapy as internet-delivered vs treatment as usual for medically unexplained pain: A 6-month pilot study
.
Psychosomatics
.
2016
May-Jun
;
57
(
3
):
292
300
.
[PubMed]
0033-3182
27.
Rief
W
,
Burton
C
,
Frostholm
L
,
Henningsen
P
,
Kleinstäuber
M
,
Kop
WJ
, et al
Core outcome domains for clinical trials on somatic symptom disorder, bodily distress disorder and functional somatic syndromes: EURONET-SOMA recommendations
.
Psychosom Med
.
2017
;
79
(
9
):
1008
15
.
[PubMed]
0033-3174
28.
Dworkin
RH
,
Turk
DC
,
Farrar
JT
,
Haythornthwaite
JA
,
Jensen
MP
,
Katz
NP
, et al;
IMMPACT
.
Core outcome measures for chronic pain clinical trials: IMMPACT recommendations
.
Pain
.
2005
Jan
;
113
(
1-2
):
9
19
.
[PubMed]
0304-3959
29.
D’Agostino
RB
 Sr
.
Controlling alpha in a clinical trial: the case for secondary endpoints
.
Stat Med
.
2000
Mar
;
19
(
6
):
763
6
.
[PubMed]
0277-6715
30.
Sibelli
A
,
Chalder
T
,
Everitt
H
,
Chilcot
J
,
Moss-Morris
R
.
Positive and negative affect mediate the bidirectional relationship between emotional processing and symptom severity and impact in irritable bowel syndrome
.
J Psychosom Res
.
2018
Feb
;
105
:
1
13
.
[PubMed]
0022-3999
31.
Kleinstäuber
M
,
Gottschalk
J
,
Berking
M
,
Rau
J
,
Rief
W
.
Enriching Cognitive Behavior Therapy with Emotion Regulation Training for Patients with Multiple Medically Unexplained Symptoms (ENCERT): design and implementation of a multicenter, randomized, active-controlled trial
.
Contemp Clin Trials
.
2016
Mar
;
47
(
1
):
54
63
.
[PubMed]
1551-7144
32.
Mewes
R
,
Rief
W
,
Stenzel
N
,
Glaesmer
H
,
Martin
A
,
Brähler
E
.
What is “normal” disability? An investigation of disability in the general population
.
Pain
.
2009
Mar
;
142
(
1-2
):
36
41
.
[PubMed]
0304-3959
33.
Kroenke
K
,
Spitzer
RL
,
Williams
JB
.
The PHQ-15: validity of a new measure for evaluating the severity of somatic symptoms
.
Psychosom Med
.
2002
Mar-Apr
;
64
(
2
):
258
66
.
[PubMed]
0033-3174
34.
Rief
W
,
Mewes
R
,
Martin
A
,
Glaesmer
H
,
Braehler
E
.
Are psychological features useful in classifying patients with somatic symptoms?
Psychosom Med
.
2010
Sep
;
72
(
7
):
648
55
.
[PubMed]
0033-3174
35.
First
MB
,
Spitzer
RL
,
Gibbon
M
,
Williams
JB
.
Structured Clinical Interview for DSM-IV Axis I Disorders (SCID)
.
New York (NY)
:
New York State Psychiatric Institute, Biometrics Research
;
1996
.
36.
Grikscheit
F
,
Weck
F
,
Hautzinger
M
,
Heidenreich
T
,
Weigel
M
,
Rudari
V
, et al
Evaluation of treatment integrity: the treatment specificity index
.
J Clin Psychol
.
2015
Jul
;
71
(
7
):
653
65
.
[PubMed]
0021-9762
37.
Rief
W
,
Hiller
W
.
A new approach to the assessment of the treatment effects of somatoform disorders
.
Psychosomatics
.
2003
Nov-Dec
;
44
(
6
):
492
8
.
[PubMed]
0033-3182
38.
Williams
A
;
EuroQol Group
.
EuroQol—a new facility for the measurement of health-related quality of life
.
Health Policy
.
1990
Dec
;
16
(
3
):
199
208
.
[PubMed]
0168-8510
39.
Bailer
J
,
Rist
F
,
Müller
T
,
Mier
D
,
Diener
C
,
Ofer
J
, et al
German validation of the Short Health Anxiety Inventory (SHAI)
.
[Erfassung von Krankheitsangst mit dem Short Health Anxiety Inventory (SHAI)]
.
Verhaltensther Verhaltensmed
.
2013
;
34
(
4
):
378
98
.1013-1973
40.
Geissner
E
.
Coping with chronic pain - assessment of coping strategies and distress
.
Z Klin Psychol Psychother
.
1999
;
28
(
4
):
280
90
. 0300-869X
41.
Beck
AT
,
Steer
RA
,
Brown
GK
.
Beck Depression Inventory II (BDI-II). Manual
.
San Antonio (TX)
:
Psychological Corporation
;
1996
.
42.
Derogatis
LR
.
The SCL-90-R manual. Scoring and adminstration procedures for SCL-90-R
.
Baltimore (MA)
:
John Hopkins University School of Medicine
;
1983
.
43.
Berking
M
,
Znoj
H
.
Development and validation of a self-report measure for the assessment of emotion regulation skills (SEK-27)
.
[Entwicklung und Validierung eines Fragebogens zur standardisierten Selbsteinschätzung emotionaler Kompetenzen (SEK-27)]
.
Z Psychiatr Psych Ps.
2008
;
56
(
2
):
141
53
.
44.
Ladwig
I
,
Rief
W
,
Nestoriuc
Y
.
What are the risks and side effects to psychotherapy? - Development of an Inventory for the Assessment of Negative Effects of Psychotherapy (INEP)
.
[Welche Risiken und Nebenwirkungen hat Psychotherapie? – Entwicklung des Inventars zur Erfassung Negativer Effekte von Psychotherapie (INEP)]
.
Verhaltenstherapie
.
2014
;
24
(
4
):
252
63
. 1016-6262
45.
Gottschalk
JM
,
Bleichhardt
G
,
Kleinstäuber
M
,
Berking
M
,
Rief
W
.
Extension of CBT by emotion regulation training in patients with multiple somatoform symptoms
.
[Erweiterung der kognitiven Verhaltenstherapie um Emotionsregulationstraining bei Patienten mit multiplen somatoformen Symptomen: Ergebnisse einer kontrollierten Pilotstudie]
.
Verhaltenstherapie
.
2015
;
25
(
1
):
13
21
. 1016-6262
46.
Thabane
L
,
Mbuagbaw
L
,
Zhang
S
,
Samaan
Z
,
Marcucci
M
,
Ye
C
, et al
A tutorial on sensitivity analyses in clinical trials: the what, why, when and how
.
BMC Med Res Methodol
.
2013
Jul
;
13
(
1
):
92
.
[PubMed]
1471-2288
47.
Kleinstäuber
M
,
Witthöft
M
,
Hiller
W
.
Efficacy of short-term psychotherapy for multiple medically unexplained physical symptoms: a meta-analysis
.
Clin Psychol Rev
.
2011
Feb
;
31
(
1
):
146
60
.
[PubMed]
0272-7358
48.
Webb
CA
,
Derubeis
RJ
,
Barber
JP
.
Therapist adherence/competence and treatment outcome: A meta-analytic review
.
J Consult Clin Psychol
.
2010
Apr
;
78
(
2
):
200
11
.
[PubMed]
0022-006X
49.
Windgassen
S
,
Moss-Morris
R
,
Goldsmith
K
,
Chalder
T
.
Key mechanisms of cognitive behavioural therapy in irritable bowel syndrome: the importance of gastrointestinal related cognitions, behaviours and general anxiety
.
J Psychosom Res
.
2019
Mar
;
118
:
73
82
.
[PubMed]
0022-3999
50.
van Ravesteijn
H
,
Lucassen
P
,
Bor
H
,
van Weel
C
,
Speckens
A
.
Mindfulness-based cognitive therapy for patients with medically unexplained symptoms: a randomized controlled trial
.
Psychother Psychosom
.
2013
;
82
(
5
):
299
310
.
[PubMed]
0033-3190
51.
Rheker
J
,
Beisel
S
,
Kräling
S
,
Rief
W
.
Rate and predictors of negative effects of psychotherapy in psychiatric and psychosomatic inpatients
.
Psychiatry Res
.
2017
Aug
;
254
:
143
50
.
[PubMed]
0165-1781
52.
Hansen
NB
,
Lambert
MJ
,
Forman
EM
.
The psychotherapy dose-response effect and its implications for treatment delivery services
.
Clin Psychol Sci Pract
.
2002
;
9
(
3
):
329
43
. 0969-5893
53.
Munder
T
,
Flückiger
C
,
Gerger
H
,
Wampold
BE
,
Barth
J
.
Is the allegiance effect an epiphenomenon of true efficacy differences between treatments? a meta-analysis
.
J Couns Psychol
.
2012
Oct
;
59
(
4
):
631
7
.
[PubMed]
0022-0167
54.
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
55.
Guidi
J
,
Tomba
E
,
Cosci
F
,
Park
SK
,
Fava
GA
.
The role of staging in planning psychotherapeutic interventions in depression
.
J Clin Psychiatry
.
2017
Apr
;
78
(
4
):
456
63
.
[PubMed]
0160-6689
56.
Fava
GA
,
Cosci
F
,
Sonino
N
.
Current psychosomatic practice
.
Psychother Psychosom
.
2017
;
86
(
1
):
13
30
.
[PubMed]
0033-3190
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.