- GI Health Foundation

Behavioral Treatments for
Patients with IBS and
Functional GI Disorders
Douglas A. Drossman, M.D.
Drossman Gastroenterology PLLC and
UNC Center for Functional GI & Motility Disorders
University of North Carolina
Chapel Hill, NC, USA
1
Evidence for Behavioral Treatments
• Patients have high prevalence of psychosocial
co-morbidity
2
Psychiatric Comorbidity in IBS
Subjects with diagnosis (%)
0
25
50
75
100
Anxiety disorders
Affective disorders
Somatization disorder
Other disorders
Any psychiatric disorder
= range and weighted mean
Data adapted from Walker EA et al. Am J Psychiatry. 1990;147:1656-1661.
3
IBS Patients vs. IBS Nonpatients vs.
Normals SCL-90
1.5
IBS Patients
IBS Non-patients
Normals
1
Average
raw
score
.5
0
SOM
OBS
SEN
DEP
ANX
HOS
PHO
PAR
PSY
SOM – Somatization; OBS – Obsessive compulsive; SEN – interpersonal sensitivity; DEP – depression; ANX – anxiety;
HOS – hostility; PHO – phobic behavior; PAR – paranoid; PSY – psychoticism
Whitehead WE et al. Gastroenterology. 1988;95:709-714.
4
IBS - Psychosocial
IBS Non-patients
Normal
• Psychologic disturbance relates
to patients who see physicians
IBS patients
Psychologic
disturbance
• Psychosocial factors influence
health care seeking
5
Evidence for Behavioral Treatments
• Patients have high prevalence of psychosocial morbidity
• Patients have enhanced gut reactivity to stress
6
Alteration of the MMC by Psychological Stress in
Healthy Subjects and IBS Patients
8
Health
IBS
6
Number of
MMCs
4
(per 8 hr)
2
0
Asleep
MMC=migrating motor complex
McRae S et al. Gut 1982;23:404-412.
Awake
Psychological
stress
7
Effect of Stress on
Rectal Perception Threshold
Physical stress
20
20
Controls (n=12)
C-IBS (n=24)
10
% change from
baseline
Psychological stress
10
0
0
-10
*
*
-10
-20
-20
*P=.01
-30
*P=.01
IBS vs controls
-40
IBS vs controls
-30
0
5
10
Stress
15
Recovery
Time (min)
Murray CDR. Gastroenterology 2004;127:1695-1699.
20
0
5
10
Stress
15
20
Recovery
Time (min)
8
Evidence for Behavioral Treatments
• Patients have high prevalence of psychosocial morbidity
• Patients have enhanced gut reactivity to stress
• Symptom severity relates to psych disturbance
9
IBS - Predictors of Severity
15
**
*** P<.0001
** P<.001
***
Severe IBS
Moderate IBS
***
**
10
Scores*
**
***
5
0
***
BDI
CAT
SIP
* Adjusted for: Age, Race, Education
IBS /
QOL
Divided
by 10
Days in
MD
Hospital
bed
visits admits
3 mos. 3 mos. 2 yrs.
BDI=Beck Depression Inventory; IBS-QOL: IBS Quality of Life questionnaire; SIP=Sickness Impact Profile
Drossman DA et al. Am J Gastroenterol. 2000;95:999-1007.
10
IBS – Brain-Gut Influences on
Severity and Treatment
Injury
Hormones,
Peptides
Infection
Diet
Life
stress
Afferent
excitation
Psych
Diagnosis Poor
coping
Abuse
Disinhibition
Mild
Moderate
Lifestyle
Gut medications
Diet
Severe
Antidepressants
Behavioral Rx
11
Effect on Perception
CNS Effects
Number of
symptoms
Somatic / visceral sensations
12
Evidence for Behavioral Treatments
• Patients have high prevalence of psychosocial morbidity
• Patients have enhanced gut reactivity to stress
• Symptom severity relates to psych disturbance
• Cognitive bias increases symptom behaviors:
‒ Catastrophizing
‒ Perceived ability to decrease or control symptoms
13
Coping Strategies Questionnaire (CSQ)
• Catastrophizing: Maladaptive negative cognitions:
‒ “It’s terrible and I feel it will never get better”
‒ “I worry all the time whether it will end”
• Control: “How much control do you feel you have over
your symptoms?”
• Decrease: “How much are you able to decrease your
symptoms?”
14
Poor Health Outcome - 1 Year
Variable
Std. b
P<
Education
-0.139
0.05
Abuse severity (0-6)
0.338
0.0001
Revised WOC - PPS
0.166
0.05
CSQ - catastrophizing
0.177
0.04
CSQ - decrease symptoms
0.251
0.003
R2 - overall poor health
41%
Not significant: Age, race, diagnosis, neuroticism, other Ways of
Coping scales, CSQ - Ability to Control Symptoms
CSQ=Coping Strategies Questionnaire
Drossman DA et al. Psychosom. Med. 2000;62:309-317.
15
Cognitions
• Catastrophizing
‒ the tendency to exaggerate the threat of certain symptoms
• GI specific anxiety
‒ heightened sensitivity to, and fear of, anxiety-related
GI sensations
• Health anxiety
‒ worry about bodily symptoms
• Selective attention
‒ to thoughts and perceptions that confirm patients’ understandings
and concerns about GI symptoms
1. Sullivan MJ et al. Clin J Pain. 2001;17:52-64; 2. Taylor S et al. Behav Res Ther. 1998;36:51-57l 3. Gwee KA et al. Gut.
1999;44:400-406; 4. Toner BB et al. Psychosom Med. 1998;60:492-497.
16
Evidence for Behavioral Treatments
• Patients have high prevalence of psychosocial morbidity
• Patients have enhanced gut reactivity to stress
• Symptom severity relates to psych disturbance
• Cognitive bias increases symptom behaviors:
• Brain-gut physiology offers mechanistic support
‒
Effects on motility/visceral sensitivity insufficient to explain
pain responses
‒
Central areas linked to stress reactivity and pain modulation
are affected
17
Rectal Sensitivity to Distension in IBS
IBS: Lower pain threshold
50
40
AML
40
Median
pain
threshold
30
28
IBS
Control
20
10
P=.0002
0
SDT
IBS: Similar perceptual sensitivity
1.0
0.5
P=.69
0.8
0.4
Median
Median
perceptual
0.6
response 0.3
0.5
0.5
sensitivity
bias (β)
P(A)
0.4
0.2
0.2
0.1
0
0
AML=ascending method of limits; SDT=sensory decision-theory analysis.
Dorn S et al. Gut 2007; 56:1202-1207.
IBS: Higher response bias
P=.003
0.25
0.19
18
IBS - Ascending Visceral Pain Pathway
MCC
Primary
somatosensory
cortex
pACC
Thalamus
Insula
Reticulothalamic
Spinothalamic
Spinomesencephalic
Spinoreticular
Dorsal
reticular
nucleus
Colon
MCC=midcingulate cortex; pACC=perigenual ACC
Heimer L. In: The Human Brain and Spinal Cord. Springer-Verlag, New York, New York; 1995:201-216.
19
Descending Visceral Pain Pathway
ACC
Thalamus
PAG
Locus coeruleus
Caudal raphe
nucleus
Amygdala
Noradrenergic
Serotonergic
Rostral
ventral
medulla
Opioidergic
Colon
ACC=anterior cingulate cortex; PAG=periaqueductal gray
Heimer L. In: The Human Brain and Spinal Cord. Springer-Verlag, New York, New York; 1995:201-216.
20
Increased dACC in IBS Consistent with
Greater Affective Pain Experience
55 mmHg of Distension
45 mmHg of Distension
ACC
Brainstem/PAG
ACC=anterior cingulate cortex; PAG=periaqueducal gray; PCC=posterior cingulate cortex; PFC=prefrontal cortex
Verne, et al., Pain, 2003
Naliboff et al, Psychosom Med 2001;
21
IBS + Abuse vs. Others (50 mm Hg)
P=.004
5
Pain Covariate (50 mm Hg)
Pain ratings
4
3
2
1
0
IBS /
Abuse
n=5
ACC=anterior cingulate cortex; MCC=midcingulate cortex; periaqueducal gray; PCC=posterior cingulate cortex
Ringel Y, Drossman DA, Gastroenterology 2008; 134:396-412.
All
others
n=14
22
Evidence for Behavioral Treatments
• Patients have high prevalence of psychosocial morbidity
• Patients have enhanced gut reactivity to stress
• Symptom severity relates to psych disturbance
• Cognitive bias increases symptom behaviors:
• Brain-gut physiology offers mechanistic support
• Improvement with psychological treatments
associated with brain imaging changes
23
IBS - CNS Response to Somatic Pain
during Hypnosis
Somatosensory
cortex
High
Low
t-value
- 6.00
- 5.00
- 4.00
- 3.00
Low
High
Rainville Science 1997; 277:968
Anterior
cingulate
cortex
Unpleasantness
24
Severe IBS / Psychological Distress
Clinical Recovery (8 months later)
8
6
4
Z=+44
BA
40
+38
MCC
+24
SI
also
+38
+14
+10
BA BA
22 6/44
+2
Ant.
ins.
2
MCC=midcingulate cortex
Drossman DA et al. Gastroenterology. 2003;124:754-761.
25
Evidence for Behavioral Treatments
• Patients have high prevalence of psychosocial morbidity
• Patients have enhanced gut reactivity to stress
• Symptom severity relates to psych disturbance
• Cognitive bias increases symptom behaviors
• Brain-gut physiology offers mechanistic support
• Improvement with antidepressant and psychological
treatment associated with brain imaging changes
• Clinical trials show improvement
26
Psychological Therapies
Subgroup analysis according to type of therapy
Trials
N
RR
95% CI
NNT
95% CI
Cognitive behavior therapy
7
491
0.60
0.42 – 0.87
3
2-7
Relaxation training
5
234
0.82
0.63-1.08
Dynamic psychotherapy
2
273
0.60
0.39-0.93
3.5
2-25
Hypnotherapy
2
40
0.48
0.26-0.87
2
1.5-7
NNT=number needed to treat; RR=relative risk.
Ford AC et al. BMJ. 2008; 337;a2313
27
If you are distressed by anything external,
the pain is not due to the thing itself,
but to your estimate of it;
and this you have the power to
revoke at any moment.
Marcus Aurelius Antoninus
Roman Emperor, A.D. 161-180
28
IBS - Psychological Treatments
• Cognitive - behavioral
− Uses diaries and exercises to reframe maladaptive thoughts and
increase control over symptoms
• Psychotherapy - Interpersonal
− Identify and address difficulties in relationships and emotional conflicts
via bowel symptoms
• Hypnosis
− Suggestion used to produce overall relaxation and reduce gut
sensations
• Relaxation training
− Uses imagery and relaxation techniques to reduce autonomic arousal
and stimulate muscular relaxation
Drossman DA et al. Gastroenterol Int. 1995; 8:47-90.
29
Psychological Treatments - FGIDs
•
Addresses thoughts, behaviors, and responses
that result from patients’ experiences
Cognitive Behavioral
Therapy
•
Relaxation/stress
management
•
Helps to recognize
relationship between
beliefs and symptoms
30
Cognitive Triad
Depression, Anxiety
and Poor Coping
Negative
Emotions
Negative
Experiences
31
CBT vs EDU and DES vs PLA
for Moderate to Severe FBD
CBT/EDU Responder Analysis*
DES/PLA Responder Analysis*
100
100
P<.0001
P=.0002
P=.128
80
80
60
60
P=.006
%
%
40
40
20
20
0
P=.021
n=110
n=51
CBT EDU
Intention to
Treat
n=100 n=46
0
CBT EDU
Per Protocol
n=107 n=57
n=89 n=80 n=55
DES PLA
DES DES PLA
detectable
Per Protocol
Intention to
Treat
*Responder defined as % ³3.5 on Satisfaction scale at end of treatment
CBT=cognitive behavioral treatment; DES=desipramine; EDU=education; PLA=placebo
Drossman DA et. al. Gastroenterology. 2003;125:19-31.
32
Psychological Treatments - FGIDs
• The relationship between the patient and the therapist is
used as the primary vehicle for change
Psychodynamic
Interpersonal Therapy
• Focuses on factors within relationships that contribute to
the persistence of pain and the chronicity of symptoms
33
Health Care Costs
P<.05
1800
1600
1400
Psychotherapy
Paroxetine
Usual care
1200
$
1000
800
600
P<.05
400
200
0
Treatment period
Creed F et al. Gastroenterology 2003; 124:303-313.
Follow-up year
34
Psychological Treatments - FGIDs
• Creates a relaxing, calming image to focus away
from uncomfortable symptoms to more pleasant
perceptions
Hypnosis
• Heightened suggestibility
that encourages a more
positive state
• Suggestions made to
retain these positive and
pleasant perceptions
35
Hypnosis
Image:
A calm river
Rough
water:
Severe
pain
Heavy
focus on
pain
Refocus:
No pain
Heightened
suggestibility
Can’t
cope
36
Randomized Controlled Trial of Hypnosis
Treatment for Severe Refractory IBS
Pain
18
16
Psychotherapy
+ placebo pills
(15 patients)
Mean
12
Distension
Psychotherapy
+ placebo pills
(15 patients)
14
10
8
Hypnosis
(15 patients)
Hypnosis
(15 patients)
6
4
2
0
0
0
Weeks
12
0
Weeks
12
n=30
Whorwell P et al. Lancet 1984;2:1232-1237.
37
When to Refer for Psychotherapy
38
When to Refer for Psychological Treatment
• Consider referral for:
−
Moderate-severe symptoms (better if not constant pain)
−
When patient sees relation of stress to symptoms
−
Maladaptive coping (eg, “catastrophizing”)
−
Is motivated toward treatment
• No one treatment is superior
• Predictors of treatment response:
− Confidence in treatment success
− Perceived sense of control over symptoms
− Good relationship with therapist
Weinland SR et al. Am J Gastroenterol. 2010;105:1397-1406.
39
Symptom severity
Psych distress
Disability
Previous therapy
Severity
Red Flags
Mental Health Consultation
• Severe depression /
suicidal
• Difficulties in physician –
patient interaction
• Chronic refractory pain
• Idiosyncratic health beliefs
• Severe disability
• Other identifiable
psychological difficulties
(somatization disorder, PTSD,
severe anxiety, abuse)
• Maladaptive illness
behavior
40
Targets for Psychological Treatment of FGID
Maladaptive
Disease Model
Maladaptive
Psychological Adjustment
• Maladaptive beliefs
• Catastrophizing
• Symptom specific anxiety
Overactive
Stress Response
• Response to general stress
• Sick-role
• Shame/guilt
• Response to FGID
symptoms
41
Benefits of Psychological Treatment
• High response rate (about 70%)
• Can benefit patients not responding to medical treatments
• Is additive to and possibly synergistic with medical
treatments
• No side effects
• Benefits continue years after treatment ends
• Reduces health care costs
42
Limitations of Psychological Treatment
• Requires patient motivation:
− Needs to understand and accept the process without stigma
− Frequent visits
− Home exercises
− Treatment costs
• Requires trained therapist in community
• Therapist must be experienced working with GI disorders
• Poor reimbursement from 3rd party payers
• Usually requires ongoing medical care
43
Gate Control Theory
Pain
Midbrain
Inhibitory
Pathway
Inhibits
Spinal Cord
Intestinal
Afferent
Receptor
Pain
Gate
44
Effect on Perception
Perception
Threshold
Somatic / Visceral Sensations
45
Combining Antidepressants +
Psych Treatments
• Clinical Observations
− Antidepressants improve pain, vegetative signs and hopelessness,
and increase motivation for psych treatments
− Psychological treatments improve coping, cognitive function, and
effects of trauma, and increase adherence to medication
• Brain Imaging
− Antidepressants may have “bottom up” effects, acting on
paralimbic (cingulate, insula)
− Psychological treatments may have “top down” effects on
prefrontal cognitive areas improving “executive” function
• Clinical trials show combined treatments > monotherapy
for headache, depression and other psych disorders
46
Key Clinical Points
• Behavioral treatments act primarily centrally
− Improved global responses and emotional distress, and reduced
depression (higher dosages)
− Improved coping and appraisal of pain
(“I still feel the pain but can deal with it”)
− Improved central pain modulation via cingulate cortex
• No benefit for one treatment over another
− Decision based on availability and skill of therapist(s)
• Behavioral treatments show continued benefit and may
save costs 1 year after treatment
• Combined treatments (antidepressants + psych) may
show enhanced (synergistic) effect
47
END
48
49
“. . . physical pain and the more
psychological pain of rejection are
processed by the same areas of the brain.”
50
Reduction in Activity After
Cognitive Therapy* (PET)
*Associated with improved pain and bowel dysfunction
and reduction in anxiety
Lackner A, et al., Gastroenterology 2004 Abstract
51
Composite Scores and Components
for Combined Treatment
CBT+DES
EDU+PLA
p value
.49 (0.01)
.42 (0.02)
0.0004
Satisfaction
3.56
3.11
<0.0001
IBS-QOL
76.4
72.9
0.03
49.8%
41.2%
0.15
9.25
10.5
0.097
Composite Score (SE)
Global Well-Being
McGill
52