A biopsychosocial

approach to

constipation

Kyle Staller, MD, MPH

Director, GI Motility Laboratory, MGH

Center for Neurointestinal Health

Clinical and Translational Epidemiology Unit

NESGNA Fall Conference, October 12, 2017

Disclosures

• Research support from Astra-Zeneca, Gelesis, and

Pathway Genomics

2

What is normal?

Am J Gastroenterol. 2017 Aug 1.

• Overall the “3 by 3” metric

most understood by lay public:

– Normal is from 3 bowel

movements/day to 3 bowel

movements/week)

What is constipation: Rome criteria

4

Gastroenterology. 2016; Feb 15; 150:1393-1407.

• Requires ≥2 of the following symptoms with

chronicity:

– Hard stools

– Straining

– Incomplete evacuation

– Sensation of blocked evacuation

– Vaginal or perianal pressure needed to facilitate

defecation

– <3 bowel movements per week

• No loose stools without laxatives

• No secondary cause of constipation (i.e.

opioids)

Background: burden of constipation

5

Am J Gastroenterol. 2011 Sep;106(9):1582-91

• Affects 55 million Americans (Women: 16%, Men 12%,

Elderly 40%)

Background

• Our current understanding of constipation based

on physiology with 3 subtypes:

– Slow-transit constipation

– Pelvic floor dysfunction

– Normal-transit constipation

Secondary causes of constipation

7Ann Intern Med. 2015 Apr 7;162(7):ITC1.

Measuring colonic transit: using a Sitz marker study

• MGH protocol:

– Patient ingests a pill containing 24 radio-opaque markers

(Day 0)

– Abdominal plain film (Day 5)

Why not treat everyone with laxatives?

• Chronic constipation is more than stool frequency

Constipation is likely a spectrum of disease

Normal-transit constipation

Isolated slow-transit

constipation

Mixed physiology

Obstructed defecation

Irritable bowel syndrome? (IBS-C)

Visceral hypersensitivity

Pelvic floor physiology

N Engl J Med. 2003 Oct 2;349(14):1360-8.

Testing for pelvic floor dysfunction:

anorectal manometry

Gastroenterology 2013 144, 211-217.

When to order anorectal manometry

• Retained markers frequently seen in patients w/

pelvic floor dysfunction undergoing transit testing

• Presumed symptoms of dyssynergic defecation:

– Painful defecation

– Straining

– Incomplete evacuation

– Sensation of blocked evacuation

– Vaginal or perianal pressure needed to facilitate

defecation

• Multiple studies have shown that the positive and

negative predictive value of symptoms alone is

inadequate for the diagnosis of dyssynergic

defecation

Am J Gastroenterol. 2014 Aug;109(8):1141-57.

Staller K et al. Am J Gastroenterol. 2015 Jul;110(7):1049-55.

Evolution of anorectal manometry technology

Water perfusion

Anorectal manometry

High resolution

Anorectal manometry

High definition (3D)

Balloon expulsion testing

Role of physical therapy in refractory constipation

Am J Gastroenterol. 2014 Aug;109(8):1141-57.

When all else fails: surgery for constipation

• Could consider diverting loop

ileostomy followed by

colectomy with ileorectal

anastomosis

• Number of colectomies for

chronic constipation is

increasing

Aliment Pharmacol Ther. 2015 Dec;42(11-12):1281-93.

Refractory constipation: colectomy

Aliment Pharmacol Ther. 2015 Dec;42(11-12):1281-93.

Refractory constipation: colectomy

Aliment Pharmacol Ther. 2015 Dec;42(11-12):1281-93.

• Growing acceptance of surgical treatment of constipation

– 14.4% of colectomies for

constipation

• High complication rate:

– ED visits or hospitalizations in 1/3 of

patients undergoing colectomy for

chronic constipation

• High healthcare resource utilization: surrogate for well-being?

Surgery for constipation: an alternative approach

Lancet. 1990 Nov 17;336(8725):1217-8.

• Malone in 1990 describes an alternative approach using the

appendix as a conduit for antegrade colonic enemas (ACE)

Dis Colon Rectum. 2007 Jan;50(1):22-8.

Surgery for constipation: an alternative approach

Lancet. 1990 Nov 17;336(8725):1217-8.

• Newer techniques using

specially-designed catheters

have significantly decreased

the complication rate

• Placement:

– Endoscopic

– Percutaneous (IR)

– Laparoscopic (surgery)

Laparoscopic Percutaneous Endoscopic Cecostomy (LAPEC)

• Technique originally described in children by Allan Goldstein

from MGH

• Uses colonoscopy in conjunction with laparoscopic approach

to secure cecum to abdominal wall and decrease risk of

peritoneal contamination and peritonitis

Making the jump: LAPEC in adults

• LAPEC follow-up study of mostly children and young adults:

– Few tube removals

– Overall success rate of 95%

• Now regularly performing in adults

– Joint venture with Allan Goldstein, MD and Hiroko Kunitake, MD

– Stay tuned for more data about which patients derive the most benefit

Koyfman S…Staller K. J Gastrointest Surg. 2017 Apr;21(4):676-683.

Breakdown of constipation at MGH

Staller K et al. Neurogastroenterol Motil. 2015 Oct;27(10):1378-88.

Pathophysiology of constipation

32

Gastroenterology. 2016 Feb 19. pii: S0016-5085(16)00223-7

What about IBS?

33

Gastroenterology. 2016; Feb 15; 150:1393-1407.

Recurrent abdominal pain

Related to defecation

Associated with change in

frequency of stool

Associated with change in form of

stool

>1 day/week in last 3 weeks

+ 2 or more of

IBS subtypes

Gastroenterology. 2016; Feb 15; 150:1393-1407.

Impact of IBS on quality of life varies by stool form

35

Am J Gastroenterol. 2012 Feb;107(2):286-95.

Impact of IBS on quality of life varies by subtype

36

Am J Gastroenterol. 2012 Feb;107(2):286-95.

Psychosocial factors in constipation

• Prevalence of comorbid psychiatric

disease rages from 40-90% among

IBS patients at a tertiary care center

• Women with IBS are more likely to

have experienced childhood verbal,

sexual, or physical abuse

– Leads to persistent changes in

the brain-gut axisresults in

perception of otherwise

unconscious input from GI tract

37

JAMA. 2015 Mar 3;313(9):949-58.

Non-laxative medications

for constipation/IBS

38

Use of neuromodulators in IBS with constipation

• Neuromodulators reduce

global IBS symptoms and

abdominal pain in IBS

patients1.

• Benefits:2.

1. Reduction in pain

2. Treatment of psychological

distress

3. Treatment of comorbid

psychiatric disease

4. Leverage motility effects

5. Long-term treatment may

reverse maladaptive brain

changes

Potential actions of

antidepressants in IBS

Antidepressant

action

Visceral

analgesia

Changes in

motility

Smooth muscle

relaxation

1. Am J Gastroenterol. 2014;109:1350-1365.

2.Am J Gastroenterol. 2017 May;112(5):693-702

Dietary treatments for

constipation symptoms

40

Patient demand for dietary advice in constipation

outstrips the supply of available evidence for providers

• More than 70% of IBS patients

believe that food plays a role in

their symptoms1.

• Self-reported food intolerance in

IBS is associated with more

severe symptom severity2.

• Evolution of concept of non-

celiac gluten (wheat) sensitivity

41

1. Clin Gastroenterol Hepatol 2015.

2. Clin Gastroenterol Hepatol. 2015 Nov;13(11):1899-906.

Worsening of symptoms in IBS patients with blinded

re-introduction of gluten

42

Am J Gastroenterol. 2011 Mar;106(3):508-14

Lentils, cabbage, brussels sprouts,

asparagus, green beans, legumes

Sorbitol

Raffinose

Honey, apples, pears, peaches,

mangos, fruit juice, dried fruit

Apricots, peaches, artificial sweeteners,

artificially sweetened gums

Wheat (large amounts), rye (large

amounts), onions, leeks, zucchini

Excess

Fructose

Fructans

Fermentable oligo-, di-, monosaccharides and polyols

What are FODMAPs?

Milk (cow, goat, or sheep), custard,

ice cream, yogurt, soft unripened

cheeses (eg, cottage cheese, ricotta)

Lactose

1. Clin Gastroenterol Hepatol. 2008;6:765-771.

2. J Am Diet Assoc. 2006;106:1631-1639.

3. Ther Adv Gastroenterol. 2012;5:261-268

Gastroenterology. 2013;145:320-328.

Which diet to choose? Gluten-free or low-FODMAP?

Low FODMAP run-in Blinded re-introduction

of high FODMAP foods

Low FODMAP diet has a differential effect on IBS

patients compared to healthy controls

45

Gastroenterology. 2014 Jan;146(1):67-75.e5.

Other non-pharmacologic

treatments for

constipation/IBS

46

Questions about probiotics are a reality of taking

care of patients with IBS

• Probiotics likely provide some benefit

to patients with IBS

• On the whole, products containing

Bifidobacterium (either alone or in a

cocktail) are effective in IBS

• Best quality data is for

Bifidobacterium infantis 35624

• Recent data suggests a benefit of B.

lactis DN-173-010A in patients with

IBS-C and bloating

• Any advice to patients limited by

poor quality of existing data

47

J Clin Gastroenterol 2015; 49: Supp. 1.

Psychological therapies improve IBS symptoms

• Psychosocial therapies have

been shown to be effective in

improving IBS symptoms

– Cognitive behavioral therapy

(CBT)

– Hypnotherapy

– Multi-component psychological

therapy

– Multi-component psychological

therapy administered by phone

– Dynamic psychotherapy

• Use limited by lack of skilled

therapists in managing IBS

Am J Gastroenterol. 2014;109(Suppl 1):S2-S26.

What type of constipation patient am I seeing today?

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Clinical feature Mild (40%) Moderate (35%) Severe (25%)

Physiological factors Primarily bowel dysfunctionBowel dysfunction and CNS

pain dysregulation

Primarily CNS pain

dysregulation

PsychosocialNone or mild psychosocial

distressModerate psychosocial distress

Severe–high psychosocial

distress, catastrophizing, abuse

history

Sex Men = women Women > men Women >>> men

Age Older > younger Older = younger Younger > older

Abdominal pain Mild/intermittent Moderate, frequentSevere/very frequent or

constant

Number of other

symptomsLow (1–3) Medium (4–6) High (≥7)

Health-related

quality of lifeGood Fair Poor

Health care use 0–1/y 2–4/y ≥5/y

Activity restriction Occasional (0–15 days) More often (15–50 days) Frequent/constant (>50 days)

Work disability <5% 6%–10% ≥11%

Adapted from Gastroenterology. 2016 Feb 19. pii: S0016-5085(16)00223-7.

Explaining the biopsychosocial model of constipation

to patients

• Start with transit description

– Most intuitive how most people

(including MDs) think about

constipation

• Describe pelvic floor

dysfunction using physiologic

explanation

• Visceral hypersensitivity

– Artificial to think about gut motility

in isolation

– Normal gut sensations improperly

amplified in PNS and CNS

– Abnormal sensory response to

colonic stool burden

Treatment of constipation is a “3-legged stool”

1. Address underlying colonic transit disturbances

– Motility agents (laxatives)

– Don’t be surprised if:

normalization of bowel movements ≠ resolution of symptoms

– Surgery utilized very cautiously

2. Treat visceral hypersensitivity and IBS overlay

– Neuromodulators with an eye toward gut transit and coexisting

motility disturbances (i.e. gastroparesis, small bowel dysfunction)

3. Consider effects of psychiatric overlay, trauma

– Introduce cognitive behavioral therapy after establishing

therapeutic relationship

Investing time up front can pay dividends later on

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Thank you

Acknowledgements:• Center for Neurointestinal Health

• Braden Kuo, MD

• Andrew Chan, MD, MPH

• Grant support from the American

Gastroenterological Association