Irritable bowel syndrome (IBS) is one of the most common disorders of gut-brain interaction (DGBI) and has a significant impact on patients and the health care system. Making the correct diagnosis can improve patient care, minimize unnecessary testing, and lead to the most appropriate treatment. In this activity, learners will review 5 IBS cases with Brian E. Lacy, MD, PhD, FACG as he discusses different aspects of patient management including diagnosis, IBS-C and IBS-D treatment, pain management, and improving patient-provider communication.

1. Jointly Provided by
Case Closed:
Optimizing IBS Management
Chair
Brian E. Lacy, PhD, MD, FACG
Professor of Medicine
Mayo Clinic
Jacksonville, FL
|

2. Disclosures
u Brian E. Lacy, PhD, MD, FACG, discloses that he
has served on the advisory board for Allergan,
Ironwood/AbbVie, and Salix. Dr. Lacy has also
served as a consultant for Allakos, Gemelli, Sanofi,
and Viver.

3. Learning Objectives
After participating in all 5 modules, learners will be
able to:
u Evaluate approaches for the timely recognition
and diagnosis of IBS
u Identify optimal treatment strategies per current
IBS guidelines
u Assess current and emerging strategies for
managing IBS-related pain
u Discuss shared decision-making and patient
communication strategies for IBS patients

4. Overview
u IBS is one of the most common disorders of gut-
brain interaction (DGBI)
u IBS has a significant impact on patients and the
health care system
u Making the correct diagnosis can be
accomplished efficiently
u Making the correct diagnosis will improve patient
care, minimize unnecessary testing and lead to
the most appropriate treatment
u Better communication will improve patient care
and reduce burden to the health care system

5. Making the Diagnosis
Case Closed: Optimizing IBS Management

6. Objectives
u Review 5 key features to make a positive
diagnosis of IBS
u Consider key supporting diagnoses that
increase the likelihood of having IBS
u Understand the Rome IV criteria for the
diagnosis of IBS
u Recognize the 3 main subtypes of IBS
u Evaluate the role of limited diagnostic testing

7. Case Study
u A 28-year-old IT tech is referred to you for further management
u Symptoms started after a trip to Central America one year ago
where he and his girlfriend both developed severe food
poisoning
u Since then, he has had symptoms of daily loose, watery, non-
bloody, urgent bowel movements. He feels bloated and
distended. He reports daily pain in his lower abdomen that
worsens just before a bowel movement and improves after
having urgent diarrhea
u His weight has remained stable. He does not report fevers, chills,
rashes, oral ulcers, myalgias or arthralgias
u He does not take any medications or use alternative therapies.
PMH and PSM are unremarkable. He does not have a family
history of IBD, celiac disease, or colorectal cancer

8. Case Study - Continued
u Laboratory studies immediately after returning to
the US were all normal (CBC, CMP and stool studies
[including parasites])
u Follow-up blood work 6 months later, including
celiac serologies, were all normal
u His girlfriend’s symptoms resolved within 2 weeks
u A lactose-free diet of 2 weeks did not help
u A breath test for SIBO was negative
u PRN loperamide has not helped his abdominal
pain, bloating, or diarrhea
u He asks: What is the diagnosis, and what
treatments are available?
CBC, complete blood count; CMP, complete metabolic panel; PRN, as needed; SIBO, small intestinal bacterial
overgrowth.

9. Audience Response
u What laboratory tests are required in all patients
to make the diagnosis of IBS using the Rome IV
criteria?
u A. CBC, BMP, TSH
u B. CBC, BMP, celiac serologies, CRP
u C. BMP, TSH, celiac serologies
u D. CBC, cortisol, TSH, CRP
u E. None of the above
BMP, basic metabolic panel; CBC, complete blood count; CMP, complete metabolic panel; CRP, C-reactive protein;
TSH, thyroid stimulating hormone.

10. Audience Response
u To make an accurate diagnosis of IBS using the
Rome IV criteria, abdominal pain should occur, on
average, how frequently during the past 3 months?
u A. Daily
u B. At least 5 times per week
u C. At least 3 times per week
u D. At least weekly
u E. At least monthly

11. The diagnosis of IBS can be tricky: no
mathematical formula can make the
diagnosis
Abdominal pain3
Constipation/Diarrhea
Diarrhea
X Bloating
Depression-3 + Anxiety-2
Anemia + Nocturnal symptoms
∑ ∫
+ ∆
Extraintestinal symptoms
+
Intestinal non-IBS symptoms
r +
-3
X
*And no laboratory biomarker exists

12. In clinical practice, IBS can be a difficult
diagnosis to make because…
u Symptoms fluctuate over time
u Symptoms don’t always respond to appropriate
therapy
u Other disorders can mimic IBS
u A laboratory biomarker does not exist
u Guidelines/criteria are not always employed
Lacy et al, 2021.

13. The Positive Diagnosis of IBS:
5 Key Features
u Clinical history – symptoms are still the key
u Co-morbid conditions
u Alarm/warning signs
u Physical examination – include a DRE
u Rome IV criteria
u Minimal (limited) laboratory tests
u When clinically indicated, colonoscopy or other
appropriate tests
DRE, digital rectal exam.
Ford, Lacy & Talley, 2017.

14. Making the Diagnosis: Supporting
Symptoms and Comorbid Conditions
Supporting symptoms
u Bloating
Co-morbid conditions
u GERD
u Globus
u Non-cardiac chest pain
u Dyspepsia
u Migraine headaches
u TMJ syndrome
u Fibromyalgia
u Interstitial cystitis
u Dyspareunia
u Chronic back pain
GERD, gastroesophageal reflux disease; TMJ, temporomandibular joint.

15. Alarm Features for Organic Disorders
u Unintended weight loss (>10% in 3
months)
u Blood in stools not caused (confirmed)
by hemorrhoids or anal fissures
u Symptoms that awaken patient
u Fever
u Anemia
u Palpable mass, ascites,
lymphadenopathy
u Family history of CRC, polyposis
syndromes, IBD, or celiac disease
If alarm features are
present, investigate
and treat appropriately
CRC, colorectal cancer; IBD, inflammatory bowel disease.
Lacy et al, 2021.

16. The Value of a Physical Examination
u Organic disorders can masquerade as IBS
u New diseases/disorders develop over time
u A PE validates the patient’s reporting
u “Laying on of hands” reassures the patient
u Don’t forget checking for Carnett’s sign
u Watch for the “closed eyes” sign
u Pelvic floor dyssynergia can be identified
PE, physical examination.

17. Rome IV Criteria for IBS
Criteria fulfilled for the last 3 months with symptom onset
at least 6 months prior to diagnosis
Associated with
a change in frequency
of stool
Associated with a
change in
form of stool
Related to defecation
Recurrent abdominal pain
at least 1 day/week (on average) in the last
3 months
associated with ≥2 of the following:
Lacy et al, 2016.

18. Rome IV: Limited Diagnostic Tests Helps
Make a Positive Diagnosis
u In the appropriate patient, consider:
u “The 4 C’s” - CBC, CRP, fecal calprotectin
u Celiac serologies
u All patients do not require testing
u No role for colonoscopy in all patients
u No good biomarker yet
u Take Home Message: Make a positive diagnosis
based on symptoms & limited testing and initiate
treatment – ideally at the first visit

19. Summary
u Be confident about making the diagnosis of IBS
u The combination of a careful history, a guided PE,
limited laboratory tests and the Rome IV criteria is
safe, practical, accurate, and efficient
u Identifying the correct subtype is important as
multiple treatment options are now available for
both IBS-C and IBS-D

20. Treatment of IBS-C
Case Closed: Optimizing IBS Management

21. Objectives
u Recognize the array of treatment options
available for IBS-C
u Understand the importance of assessing disease
severity
u Review FDA approved medications for the
treatment of IBS-C

22. Case Study
u 41-year-old Associate Professor of biology
diagnosed with IBS-C using Rome IV criteria
u No warning signs on exam or history
u Recent colonoscopy (normal) performed due to
persistent symptoms and failure to respond to fiber
and PEG
u No evidence of pelvic floor dyssynergia on rectal
examination or anorectal manometry
u Not on opioids, TCAs, or anti-psychotic agents
u Her question: Are other treatments available?
PEG, polyethylene glycol; TCA, tricyclic antidepressants.

23. Audience Response 1
u How many FDA-approved medications are there
for IBS-C?
a. 1
b. 2
c. 3
d. 4
e. 5

24. Treatment Depends on Severity of IBS
vDiet, lifestyle
advice
vPositive diagnosis
vExplain, reassure
vFollow-up visit
vManage stress
vDrug therapy
+
vPsychological treatments
vGoal: improved function
vContinuing care
+
Mild
(40%)
Moderate
(35%)
Severe
(25%)
Lacy et al, 2016; Lacy et al, 2021.

25. Medical Treatments for IBS-C
u Probiotics
u Little data to support their use
u Fiber
u Osmotic agents
u Chloride channel activators
u Guanylate cyclase C agonists
u NHE3 inhibitors
u 5HT4 agonists
u CAM
CAM, complementary and alternative medicine.
Lacy et al, 2021.

26. PEG 3350+E Improves SBMs in IBS-C but not
Pain
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
# SBMs Pain Level
Mean
at
Week
4
Placebo (n=71)
PEG 3350+E
(n=68)
*
*P < 0.0001
PEG = polyethylene glycol; SBM, spontaneous bowel movement.
Chapman et al, 2013.
PEG 3350+E is not approved for use in the US

27. Lubiprostone for IBS-C: Data from 2 Phase
III Trials
Overall
responders
(%)
n=387
n=780
Lubiprostone
8 mcg BID
Placebo
* P=0.001
17.9
10.1
0
25
50
• 12-week treatment period
• Overall responder = monthly responder
for at least 2 of 3 months
• Monthly responder = at least moderate
relief for 4/4 weeks or significant relief
for 2/4 weeks
Lubiprostone is a prostaglandin E1 analog that binds to type 2 chloride channels
Approved for the treatment of women with IBS-C – 8 mcg BID
BID, twice daily.
Drossman et al, 2007.

28. Efficacy of Linaclotide in Patients With IBS-C
CSBM
Mean
Change
from
Baseline
+/-
SEM 3
2
1
0
Weeks
BL 1 2 3 4 5 6 7 8 9 10 11 12
Treatment Period*
Treatment Period
Placebo
Linaclotide 290 µg
12 13 14 15 16
RW Period†
RW Treatment Sequence
Placebo/linaclotide 290 µg
Linaclotide 290 µg/linaclotide 290 µg
Linaclotide 290 µg/placebo
z
Weeks
N=800
*P < 0.0001 for linaclotide patients vs placebo patients (ANCOVA).
†
P < 0.001 for linaclotide/linaclotide patients vs linaclotide/placebo patients (ANCOVA).
ANCOVA, analysis of covariance; CSBM, complete spontaneous bowel movement; RW, randomized withdrawal; SEM, standard error
of mean.
Rao et al, 2012.

29. Linaclotide Phase 3 IBS-C Trial: Abdominal
Pain Over 26 Weeks
ITT population, observed cases, LS-mean presented: P-values based
on ANCOVA at each week. Bars represent 95% CI.
P=0.0007 for week 1
P<0.0001 for weeks 2-26
Change
in
Worst
Abdominal
Pain,
%
-60
-50
-40
-30
-20
-10
0
Trial Week
BL 2 4 6 8 10 12 14 16 18 20 22 24 26
Linaclotide 290 µg Placebo
N=804
CI, confidence interval; ITT, intention to treat; LS, least squares.
Chey et al, 2012.

30. Plecanatide
u 16 aa peptide analog of uroguanylin
u Activates guanylate cyclase C receptors (GC-C)
with increase in intestinal fluid secretion
u FDA approved:
u CIC (2017)
u IBS-C – 1-24-18
aa, amino acid; CIC, chronic idiopathic constipation.
Miner et al, 2017; Rao, 2018.

31. Plecanatide for IBS-C: Rome III Patients
Placebo
(n=733)
Plecanatide 3 mg once daily
(n=728)
Plecanatide 6 mg once daily
(n=728)
16
25.7 26.6
0
20
40
60
80
100
P<0.001
Responders,
%
Overall
Responders*
P<0.001
27.3
36.8 39.1
0
20
40
60
80
100
Responders,
%
Abdominal Pain
Responder*
P<0.001
P<0.001
31.4
40.9 41.9
0
20
40
60
80
100
Responders,
%
Weekly Stool Frequency
Responder*
P<0.001
P<0.001
*Responder defined as a patient who was both an Abdominal Pain responder
(≥ 30% reduction in worst abdominal pain) and Stool Frequency Responder (an
increase of ≥ 1 CSBM from baseline), in the same week, for ≥ 6 weeks of the 12
treatment weeks.
Brenner et al, 2018.

32. Audience Response 2
u What class of medication is tenapanor?
a. Stimulant laxative
b. Neuromodulator
c. Sodium-hydrogen exchange inhibitor
d. GC-C agonist

33. Tenapanor & IBS-C*
u Inhibits NHE3 – sodium/hydrogen exchanger
u Randomized, double-blind, placebo-controlled trial
u Patients with IBS-C (modified Rome III criteria) with an
average of <3 CSBM/week, ≤5 SBM (spontaneous bowel
movement)/week, and abdominal pain ≥3 (0–10 rating
scale) during a 2-week screening period
u Tenapanor 50 mg BID or placebo over a 12-week treatment
period, followed by 4-week randomized withdrawal period
u Primary efficacy endpoint was the combined responder rate
(≥30% abdominal pain reduction and ≥1 CSBM increase in
the same week for ≥6 of 12 weeks)
*FDA approval: 9-13-2019

34. Tenapanor in IBS-C: Results
Responder analysis
≥6 of 12 weeks
Combined
responder
≥30%
abdominal pain
reduction and
≥1 CSBM
increase in the
same week
CSBM
responder
≥1 CSBM
increase and
≥3
CSBM/week
Abdominal
pain
responder
≥30%
abdominal
pain reduction
P=0.27
Placebo Tenapanor 50 mg BID
18.7
29.4
33.1
27
33.9 33.9
0
10
20
30
40
P=0.008
P=0.020
Responders,
%
3.3 5
19.4
13.7
16.9
30.3
0
10
20
30
40 P=0.003
P<0.001
P<0.001
Responder analysis
≥9 of 12 weeks
Combined
responder
≥30% abdominal
pain reduction and
≥1 CSBM
increase and ≥3
CSBM in the
same week
CSBM
responder
≥1 CSBM
increase and
≥3
CSBM/week
Abdominal
pain
responder
≥30% abdominal
pain reduction
Responders,
%
Chey et al, 2020.

35. Tegaserod for IBS-C in Women:
Pooled Analysis
OR, odds ratio.
Shah et al, 2021.

36. Summary
u IBS is a constantly evolving field
u Our understanding of IBS physiology continues to
expand
u Assess disease severity when considering
treatment options
u Five FDA approved treatments are now available
for IBS-C

37. Treatment of IBS-D
Case Closed: Optimizing IBS Management

38. Objectives
u Review treatment options for IBS-D
u Review data for FDA approved medications for
IBS-D

39. IBS-D Audience Question 1
How many FDA-approved medications are
available to treat IBS-D symptoms?
a. 1
b. 2
c. 3
d. 4
e. 5

40. Case Study
u 36-year-old man with post-infection IBS
u Meets Rome IV criteria; no warning signs
u Normal: labs, stool studies, colonoscopy & Bx
u No help with diet (low gluten, low FODMAP diet)
u Trial of ciprofloxacin – 500 mg BID x 2 weeks by
another provider – no help
u He is referred for another opinion due to persistent
abdominal pain, bloating, diarrhea
u What other options do you have?

41. Medical Treatments for IBS-D
u Diet
u Probiotics
u Anti-diarrheal agents
u Smooth muscle anti-spasmodics
u Bile acid sequestrants
u 5-HT3 antagonists
u Neuromodulators (e.g., tricyclic antidepressant)
u Antibiotics
u Mu-opioid agonists/delta-opioid antagonists
u Psychological interventions
u Other: CAM, glutamine
CAM, complementary and alternative medicine.
Ford, Lacy & Talley, 2017.

42. Forest plot of randomized controlled trials of probiotics vs placebo
in IBS: effect on global symptom or abdominal pain scores
Ford et al, 2018.

43. Ondansetron for IBS-D
Treatment 1 Treatment 2
Washout
7
6
5
4
3
2
1
endpoint
weeks
Bristol
Stool
Form
Score
Ondansetron
Placebo
endpoint
weeks
Crossover
Effect of Ondansetron 4-8 mg TID for 5 Weeks in
Patients with Rome III IBS-D (N=120)*
*Randomized, double-blind, dose-titration study. Primary endpoint was average stool consistency in last 2 weeks of treatment. Improvements in urgency,
frequency, bloating but NOT pain.
TID, three times daily.
Garsed et al, 2014.

44. Alosetron: Therapeutic Gain for IBS-D*
Study N
Female,
%
Response:
Alosetron, %
Response:
Placebo, %
Therapeutic
Gain, %
Camilleri1 370 53 60 33 27
Camilleri2 647 100 41 29 12
Camilleri3 626 100 43 26 17
Lembo4 801 100 73 57 16
Jones5* 623 100 58 48 10
*Comparison mebeverine† instead of placebo
†Mebeverine not available in the US
*FDA approved 2002 – women only, who have failed standard therapy.
1. Camilleri et al, 1999; 2. Camilleri et al, 2000; 3. Camilleri et al, 2001; 4. Lembo et al, 2001; 5. Jones et al, 1999.

45. Forest plot of randomized controlled trials of antidepressants
versus placebo in terms of effect on abdominal pain in IBS
Ford et al, 2019.

46. Rifaximin Trials: Global Relief of IBS Without
Constipation
u 2 Phase 3 randomized
controlled trials; N=1260
patients
u Rifaximin 550 mg TID x
2 weeks; patients followed
additional 10 weeks
u 40.7% vs. 31.7% with
adequate relief of global
symptoms (P<0.001)
0
5
10
15
20
25
30
35
40
45
T
-
I
T
-
I
I
C
o
m
b
Rifaximin
Placebo
*Rifaximin is FDA-approved for non-constipation IBS - 2015.
T-I, TARGET 1 trial; T-II, TARGET 2 trial; Comb, Combination of both trials.
Pimentel et al, 2011.

47. Target III: Retreatment with Rifaximin in IBS-D
IBS-related Abdominal Pain and Stool Consistency (Worst Case Analysis)
32.6
35.3
23.1
25.0
27.2
14.1
0
10
20
30
40
1st Repeat Tx
(Primary Endpoint)
2nd Repeat Tx Both 1st and 2nd
Repeat Tx
p = 0.0232 p = 0.0023
p = 0.0263
First and Second Repeat Treatment Phases
Rifaximin
Placebo
Responder:
Patient responding to
IBS-related abdominal
pain (≥30%
improvement) and stool
consistency (≥50%
decrease in # BMs with
type 6 or 7) from
baseline for ≥2 of the 4
weeks
N = 1074
Lacy et al, 2019.

48. Eluxadoline for IBS-D: Rationale
u Mixed mu (µ) opioid receptor agonist / delta (δ) opioid
receptor antagonist
u Low systemic absorption and bioavailability
u Low potential for drug–drug interactions
u FDA approved 2015
Activation reduces
pain, gastric
propulsion
µ opioid receptor
Inhibition restores
G-protein signalling;
reduces
µ agonist-related
desensitization
δ opioid receptor
Lembo et al, 2016; Lacy, 2016.

49. Primary Endpoint: Composite Responders –
Pooled Data
Responders
(%)
Δ 9.5*
Δ 10.3*
Δ 7.2*
Δ 11.5*
Weeks 1–12 Weeks 1–26
35
30
25
20
15
10
5
0 N=808 N=806 N=809 N=808 N=806 N=809
*p<0.001
ELX, eluxadoline; PBO, placebo.
Lembo et al, 2016.

50. Eluxadoline in IBS-D Patients Who Failed
Loperamide: RELIEF Phase 4 Study
100 mg bid vs placebo;
N = 346
Brenner et al, 2019.

51. Summary
u Multiple options are now available for treating IBS-D
symptoms
u No head-to-head data available
u Identify the predominant symptom
u Review prior therapies; don’t keep repeating what
has been done before
u Dietary interventions help some, but not all, IBS-D
patients

52. Treatment Options for
Chronic Abdominal Pain
Case Closed: Optimizing IBS Management

53. Objectives
u Define key concepts inherent to IBS patients with
chronic abdominal pain
u Appreciate the complex pathophysiology of
chronic visceral pain
u Identify key questions to make the diagnosis
u Recognize available treatment options

54. Pain Audience Response 1
Which medication is FDA-approved for the
treatment of chronic visceral pain?
a. Dicyclomine
b. Duloxetine
c. Desipramine
d. Eluxadoline
e. None of the above
f. All of the above

55. Case Study
u You are asked to see a 31-year-old woman for a second opinion re:
abdominal pain and constipation
u Onset as a teenager after a viral illness; stressful time in her life
u Persistent daily pain that prevented finishing college; unable to work
u Extensive testing without evidence of an organic disorder; normal
HRAM
u Coexisting anxiety, depression, and fibromyalgia
u She has gained weight; rare alcohol; no opioids; no cannabis
u Has failed multiple therapies (PPIs, PEG, peppermint, smooth muscle
antispasmodics, gabapentin, pregabalin, several SSRIs)
u PEG, lubiprostone, and GC-C agonists help constipation, but do not
resolve pain
u Question: What treatment options are available?
GC-C, guanylate cyclase-C; HRAM, high-resolution anorectal manometry; PEG, polyethylene glycol; PPI, proton
pump inhibitor; SSRI, selective serotonin reuptake inhibitor.

56. Chronic Abdominal Pain: Key Concepts
u Allodynia
u Noxious response to an innocuous process
u Hyperalgesia
u An exaggerated response to a noxious stimulus
u A decrease in the stimulus intensity required to elicit or
maintain nociceptor activation
u Hypervigilance
u Inappropriate focus on symptoms

57. Pathophysiology of Chronic Visceral Pain
Precipitating Factors
Perpetuating Factors
Genetics
Early trauma
Abuse
Environmental exposures
Health-care seeking behavior
Infections
Somatic illnesses
Drug abuse
Unresolved abuse
Major loss
Unresolved interpersonal difficulties
Helplessness
Vulnerability Catastrophizing
Low self-esteem
Anxiety
Depression
Predisposing Factors

58. Pain Is a Modifiable Experience
Mood
Depression
Anxiety
Psychosocial
Culture
Pain beliefs
Expectations
Conditioning
Genetics
Cognition
Attention
Distraction
Hypervigilance
Catastrophizing
Chemical/
Structural
Metabolic factors
Neurodegeneration
Abnormal plasticity
Peripheral and
central sensitization
Nociceptive modulation Amplified input

59. Evaluating the Patient With Chronic
Abdominal Pain
u Start slowly
u Take a great history
u Onset, duration of symptoms
u Relationship to meals, defecation, urination
u Dietary, medical, surgical, psychological; co-existing illnesses
u Prior tests; prior treatments
u Ask about potential alarm features
u The physical examination is important
u Assess for organic causes
u Check for Carnett’s sign
u Reassure the patient that reported symptoms are being taken
seriously
u Assess fears, concerns and goals

60. Chronic Abdominal Pain: Key Points
for the Provider
u Is the pain gastrointestinal in origin?
u Is the pain proportionate to the individual’s behavior?
u Is the pain part of an occult systemic illness?
u What is the psychological status of the patient?
u Is there a history of traumatic life events?
u Is there something to be gained by having symptoms?
u What is the patient’s understanding of the illness?
u What is the impact on daily life?
u What resources are available to the patient?
u Why now?

61. Treatment Approaches – Step 1
u Educate, reassure
u Be empathetic; be patient; avoid quick fixes
u Understand goals, fears and concerns
u Set limits
u Identify expectations
u Help the patient take responsibility (what have
you done to improve your symptoms?)
u Minimize unnecessary testing
u Lifestyle changes (exercise, better sleep, stress
reduction)
u No opioids

62. Chronic Abdominal Pain: Therapeutic Options
u TCAs
u SSRIs
u SNRIs
u Atypical agents
u CBT/hypnosis/
relaxation
u 5-HT3 antagonists
u Intestinal secretagogues
u Mixed opioid agonist/
antagonists
u 5-HT4 agonists
u Delta ligand agents
u Antispasmodics
u Peppermint oil
u Non-absorbable antibiotics
u Topiramate/tegretol
u Cannabinoids
Central
Neuromodulators
Peripheral
Neuromodulators
CBT, cognitive behavioral therapy; SNRI, serotonin and norepinephrine reuptake inhibitor.

63. Neuromodulators & DGBI*:
Analgesic Properties
u Positive monoaminergic** effects on the brain
u Improvement in pain-related brain circuits
u Modulation of the pain experience
u Improvement in mood
u Modulation of pain transmission at dorsal horn of
spinal cord
u Descending pathways from brainstem nuclei, peri-
aqueductal gray, locus ceruleus, and ventral medulla
play a critical role in pain transmission
u These projections primarily involve 5-HT and NA
*disorders of gut-brain interaction
**monoamines include serotonin (5-HT), noradrenalin (NA), and dopamine (DA)

64. TCAs: An Overview
u Two major categories
u Tertiary – amitriptyline, imipramine (clomipramine,
doxepin, trimipramine)
u Secondary – desipramine, nortriptyline
u Predominant MOA: presynaptic inhibition of NA
and 5-HT
u Tertiary TCAs – more antihistaminic and
anticholinergic effects
u Secondary TCAs – less antihistaminic and
anticholinergic effects
u Thus, less likely to cause sedation or constipation
u Most common TCA side effects
u Dry mouth, drowsiness, blurry vision, urinary retention,
dizziness, sexual dysfunction, weight gain, sweating,
cardiac arrhythmias (check an EKG at baseline)
5-HT, serotonin; EKG, electrocardiogram; MOA, mechanism of action; NA, noradrenalin; TCA, tricyclic antidepressants.
Stanculete et al, 2021.
desipramine
amitriptyline

65. Selective Serotonin Reuptake
Inhibitors (SSRIs): An Overview
u Major mechanism of action: presynaptic
inhibition of serotonin (5-HT)
u Treatment of anxiety, phobic features, OCD,
psychological distress
u No significant noradrenergic effect and thus
generally not helpful for abdominal pain
u Common AEs: agitation*, diarrhea**, HAs,
night sweats, insomnia, weight loss, sexual
dysfunction
*agitation and anxiety may occur with initiation of Tx; start at ½ dose to minimize likelihood
**diarrhea is common within first 7 days; usually transient
AE, adverse event; HA, headache; OCD, obsessive compulsive disorder.
Stanculete et al, 2021.

66. Forest plot of randomized controlled trials of antidepressants
versus placebo in terms of effect on abdominal pain in IBS
Ford et al, 2019.

67. Serotonin and Noradrenaline Reuptake
Inhibitors (SNRI): An Overview
u Major mechanism of action: presynaptic inhibition of
5-HT (serotonin) and NA (noradrenalin)
u Treatment of chronic pain syndromes (fibromyalgia,
HA, back pain)
u Formal studies are needed in DGBI
u Helpful for abdominal pain
u Generally fewer side effects than TCAs (no
antihistamine or antimuscarinic effects)
u Common AEs: nausea*, agitation, dizziness, sleep
disturbance, diarrhea, fatigue, sweats, liver
dysfunction (rare)
*usually occurs within the first week; can be reduced by taking with food
Stanculete et al, 2021.

68. Summary: Key Clinical Pearls
u The pathophysiology of chronic abdominal pain is complex
u Become comfortable with the concept of neuromodulators and get to
know one agent from each class well – dosing, efficacy, side effects
u Take time to explain why you are initiating this type of therapy
u TCAs – tertiary amines have more anticholinergic and antihistaminic
side effects (use to your advantage for IBS-D patients)
u TCAs do not slow gastric emptying at low/standard doses
u TCA doses <25 mg/day are not effective at treating visceral pain
u SSRIs cause diarrhea initially, this is transient (but let your patients know)
u SNRIs can cause nausea at the start – be prepared
u Consider augmentation therapy (combination) if only a partial
response to 1 agent

69. Improving Communication
With Your IBS Patients
Case Closed: Optimizing IBS Management

70. Objectives
u Appreciate 5 qualities of an effective patient visit
u Review key questions that will improve
communication
u Examine how more definitive language improves
communication

71. Case Study
u A 23-year-old woman is self-referred for a fourth
opinion regarding IBS symptoms
u Extensive evaluation elsewhere; all tests normal;
meets Rome IV criteria; no warning signs
u Conversation begins with “I’m here because my
doctor doesn’t know what to do. No one knows
why I have these symptoms. No one listens to me.
I’ve tried everything; nothing works. They can’t
even give me a diagnosis. You’re my last resort.”
u How do you approach this patient?

72. Audience Response
u At the start of a patient interview, the average
provider listens how long before interrupting the
patient?
a. 5 minutes
b. 3 minutes
c. 1 minute
d. 30 seconds
e. 18 seconds

73. Audience Response
u What are the 5 essential steps to ensure a fulfilling
patient visit?
a. Educating the patient, listening, reassuring, ordering
tests, scheduling a followup appointment
b. Educating the patient, listening, reassuring, making a
positive diagnosis, working on improving symptoms
c. Identifying the correct insurance plan, listening,
reassuring, ordering tests, scheduling a follow-up
d. Educating the patient, listening, reassuring, ordering
tests, setting up referrals to other specialists

74. A Patient-Centered Care Approach
u What do your patients really want from you?
u They want you to listen
u Education
u Reassurance
u A positive diagnosis
u Symptom improvement
u Treatment options explained

75. Why Is This so Hard?
u Increased patient volumes
u Decreased reimbursement
u Diminished reimbursement for cognitive tasks
u Greater administrative burden
u Paperwork/documentation drain
u Greater patient expectations

76. Why Is This Important?
u Improves diagnostic accuracy and clinical decisions
u Establishes trust
u Validates the patient’s concerns
u Creates a collaboration of care
u Collaborate - don’t compete
u Improves time efficiency
u Improves patient care and patient outcomes
u Reduces the need for additional patient testing/visits
u Improves patient satisfaction scores
u Reduces stress on the provider
u Reduces provider burnout

77. Learn to Be Empathic
u Empathy – the ability to understand and share the
feelings of another
u Seeing the world as others see it
u Being non-judgmental
u Recognizing another’s feelings and emotions
u Communicating that understanding
u “I am sure that this has been very frustrating for you”
u “I understand how hard this has been for you”
u “I can understand how hard it must be to have daily
abdominal pain”
u “I appreciate how this has affected your work/home
life”

78. Listening: Is This a Lost Art?
u Don’t be the average provider who interrupts
after 18 seconds
u Let the patient tell their story
u Listen and listen actively
u Start with open-ended questions
u “What brings you in today?”
u “How can I help you?”
u Fine-tune with close-ended questions
u “For your IBS with diarrhea symptoms, how long did you
use loperamide?”

79. Send the Right Signals
u Face the patient
u Don’t sit across a desk (remove barriers)
u Don’t type during the entire interview
u Open posture (not closed)
u Nod accordingly
u Occasionally repeat/rephrase what the patient
just told you

80. Educate & Reassure
u Docere (Latin) – doctor – to teach
u Education is therapeutic
u Make sure you use language appropriate to the patient
u Always ask about profession and education; tailor your discussion
u Remind your patient about the prevalence of IBS
u “You are not alone”
u Let them know the natural history is benign
u “This never turns to cancer”
u “This never turns to Crohn’s disease or ulcerative colitis”
u Inform them of treatment options
u “We’re lucky right now that we have a number of different options to
help improve your symptoms”

81. Make a Positive Diagnosis
u A careful history helps to exclude organic disease
and IBS mimics
u A guided physical exam reassures the patient
u Limited diagnostic testing and the Rome IV
definition cements the diagnosis
u Use positive language – don’t be wishy-washy

82. Examples of Clear vs. Qualified Language
u “you have IBS”
u “your diagnosis is”
u “your symptoms, exam
and testing are all
consistent with IBS”
u “his diagnosis is that of”
u “definitely has”
u “I have diagnosed
him/her with”
u “may be having”
u “it seems like this could
be”
u “it is possible that”
u “might fit the picture of”
u “is probably a
reasonable label”
u “working impressions”
u “managed as a case
of”
Clear Qualified
Linedale et al, 2016.

83. Before You Discuss Treatment…
Three Essential Questions to Ask
u “What do you think is causing your symptoms?”
u “For the symptoms you just described to me, do
you have any worries or concerns?”
u “What are your goals today?” (“How can I best
help you?”)

84. Wrapping Up
Explain treatment options and involve the patient
u Confidently reaffirm the diagnosis
u “You have IBS”
u Review treatment options
u Discuss efficacy, side effects, dosing, cost
u Review goals of therapy and expectations
u Involve the patient; negotiate
u Initiate therapy based on the predominant
symptom

85. Thank You for Joining Us!
u We are excited to see the impact of this
educational activity on patient care in IBS!
u In 4 weeks, you will receive a follow-up survey to
see if you’ve been able to implement any of your
intended changes as a result of what you learned
u If you have any questions, send us an email:
contact@cmespark.com

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