Treatment Algorithm for Chronic Idiopathic Constipation and Constipation-Predominant Irritable Bowel Syndrome Derived from a Canadian National Survey and Needs Assessment on Choices of Therapeutic Agents

Abstract

Background . Chronic idiopathic constipation (CIC) and constipation-predominant irritable bowel syndrome (IBS-C) are common functional lower gastrointestinal disorders that impair patients’ quality of life. In a national survey, we aimed to evaluate (1) Canadian physician practice patterns in the utilization of therapeutic agents listed in the new ACG and AGA guidelines; (2) physicians satisfaction with these agents for their CIC and IBS-C patients; and (3) the usefulness of these new guidelines in their clinical practice. Methods . A 9-item questionnaire was sent to 350 Canadian specialists to evaluate their clinical practice for the management of CIC and IBS-C. Results . The response rate to the survey was 16% ( n=55 ). Almost all (96%) respondents followed a standard, stepwise approach for management while they believed that only 24% of referring physicians followed the same approach. Respondents found guanylyl cyclase C (GCC) agonist most satisfying when treating their patients. Among the 69% of respondents who were aware of published guidelines, only 50% found them helpful in prioritizing treatment choices and 69% of respondents indicated that a treatment algorithm, applicable to Canadian practice, would be valuable. Conclusion . Based on this needs assessment, a treatment algorithm was developed to provide clinical guidance in the management of IBS-C and CIC in Canada.

Full text

Research Article
Treatment Algorithm for Chronic Idiopathic
Constipation and Constipation-Predominant Irritable Bowel
Syndrome Derived from a Canadian National Survey and
Needs Assessment on Choices of Therapeutic Agents
Yvonne Tse,1David Armstrong,2Christopher N. Andrews,3Alain Bitton,4Brian Bressler,5
John Marshall,2and Louis W. C. Liu1
1Un iversit y o f To r onto , Toron t o, ON, C a n a d a
2McMaster University, Hamilton, ON, Canada
3University of Calgary, Calgary, AB, Canada
4McGill University, Montreal, QC, Canada
5University of British Columbia, Vancouver, BC, Canada
Correspondence should be addressed to Louis W. C. Liu; louis.liu@uhn.ca
Received  July ; Revised  November ; Accepted  December ; Published  February 
Academic Editor: Dina Kao
Copyright ©  Yvonne Tse et al. is is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background. Chronic idiopathic constipation (CIC) and constipation-predominant irritable bowel syndrome (IBS-C) are common
functional lower gastrointestinal disorders that impair patients’ quality of life. In a national survey, we aimed to evaluate ()
Canadian physician practice patterns in the utilization of therapeutic agents listed in the new ACG and AGA guidelines; ()
physicians satisfaction with these agents for their CIC and IBS-C patients; and () the usefulness of these new guidelines in
their clinical practice. Methods. A -item questionnaire was sent to  Canadian specialists to evaluate their clinical practice
for the management of CIC and IBS-C. Results.eresponseratetothesurveywas%(𝑛=55). Almost all (%) respondents
followed a standard, stepwise approach for management while they believed that only % of referring physicians followed the
same approach. Respondents found guanylyl cyclase C (GCC) agonist most satisfying when treating their patients. Among the
% of respondents who were aware of published guidelines, only % found them helpful in prioritizing treatment choices and
% of respondents indicated that a treatment algorithm, applicable to Canadian practice, would be valuable. Conclusion.Basedon
this needs assessment, a treatment algorithm was developed to provide clinical guidance in the management of IBS-C and CIC in
Canada.
1. Introduction
Chronic idiopathic constipation (CIC) and irritable bowel
syndrome with predominant constipation (IBS-C) are com-
mon gastrointestinal disorders in North America, with CIC
aecting –% [] of the general population and IBS-C
aecting .% []. Canada is amongst one of the countries
that carry a high rate of IBS in the world, with a prevalence
estimated to be  in  in the population and an incidence of
, new cases per year [, ]. IBS-C is more common
in females and younger adults of less than  years of age,
whereas CIC aects females and older adults more commonly
[]. CIC and IBS-C impair patient’s quality of life (QoL), sim-
ilar to those suered from asthma and rheumatoid arthritis,
and negatively impact socioeconomics of the society [, ].
Although the Rome III diagnostic criteria dene CIC and
IBS-C as separate entities, with IBS-C being distinguished by
the presence of abdominal pain and discomfort, these criteria
cannot distinguish reliably between CIC and IBS-C. Many
patients have features of both disorders and their diagnosis
may change over time [, ]. In , America College of
Gastroenterology (ACG) published a systematic review on
Hindawi
Canadian Journal of Gastroenterology and Hepatology
Volume 2017, Article ID 8612189, 11 pages
https://doi.org/10.1155/2017/8612189

 Canadian Journal of Gastroenterology and Hepatology
the ecacy of available therapy in IBS and CIC []. Earlier
in , American Gastroenterological Association (AGA)
published a medical position statement on constipation [],
followed by an AGA guideline on pharmacological manage-
ment of IBS in  []. However, all these guidelines did
not provide direction in terms of the priority of when the
therapeutic agents are recommended to be used to optimize
management in patients suering from CIC and IBS-C.
Usinganationalsurvey,weaimedtoevaluateCanadian
specialists’ practice patterns in the utilization and satisfac-
tion of various therapeutic agents for their CIC and IBS-
C patients. e survey also addressed if the respondents
found the new ACG guidelines useful for them to prioritize
which agents to use in their clinical practice. Informed by the
result of this needs assessment survey, a treatment algorithm
was developed for the management of CIC and IBS-C. is
treatment algorithm aligned with the recently published
literature (ACG and AGA guidelines), while also considering
the limitations of these American guidelines in the Canadian
practice.
2. Methods
A questionnaire was sent to  Canadian physicians. Data
were collected over a -month period in early  (CARE,
Toronto, ON) to evaluate respondents’ area of practice and
their constipation management patterns in patients with CIC
and IBS-C.
2.1. Questionnaire. e questionnaire (the Appendix) evalu-
ated physicians’ perceptions and practices with respect to the
management options available in Canada for the treatment
of constipation in patients with CIC and IBS-C. Treatment
options were divided into stool soeners, bre supplements,
stimulant laxatives, osmotic laxatives, prokinetic agents, GCC
agonists, and “other.” Respondents were asked to rank the
order in which they would use these treatment options for
patients with inadequate bre intake, slow-transit consti-
pation, functional outlet constipation, and IBS-C and their
satisfaction with the outcomes of these treatment agents for
their patients with CIC or IBS-C. Satisfaction with treatment
response was recorded on a -point scale from  (very
unsatised),  (dissatised),  (neutral/not sure),  (satised),
to  (very satised). Additional questions regarding strategies
used by referring physicians, awareness of the most recent
ACG guidelines, and questions relating to other practice
characteristicswerealsoincluded.
2.2. Analysis of the Practice Survey. In order to statistically
determine which treatment options were considered most
satisfactory for CIC and IBS-C (the Appendix: Question
(6)(A)and(B)),thequestionswerescaledbasedontheir
rating (number of responses for a particular rating divided
bythetotalnumberofresponses)andthengroupedbased
on whether respondents thought they were not satised (the
Appendix: Question (6) ratings  and ) or satised (the
Appendix: Question (6) ratings  and ). ese 𝑡values were
then calculated to determine the clinical signicance of each.
T : Respondent demographics.
Characteristics Number (%)
Province:
(i) East Coast  (%)
(ii) Quebec  (%)
(iii) Ontario  (%)
(iv) Western Provinces (MB, AB, BC)  (%)
Specialty:
(i) Gastroenterology  (%)
(ii) Not specied/other  (%)
(iii) General surgery  (%)
Practice setting:
(i) Academic  (%)
(ii) Community  (%)
Nonclinical roles:∗
(i) Education  (%)
(ii) Research  (%)
(iii) Administrative  (%)
Patients seen monthly with chronic constipation
(i) <  (%)
(ii) –  (%)
(iii) –  (%)
(iv) –  (%)
(v) –  (%)
(vi) >  (%)
Majority of respondents were from Ontario and practiced in gastroenterol-
ogy. More than half of the respondents saw at least  patients with chronic
constipation on a monthly basis. ∗Respondents could select more than one
response.
3. Results
3.1. Practice Preferences and Satisfaction of erapeutic Agents.
Completedquestionnaireswerereturnedbyof(%)
physicians although eorts had been made to collect response
via both hardcopy survey and online survey tool with
reminders to encourage participants to respond. Table 
showed the demographic distribution of the respondents.
Almost all (%) respondents reported that they followed
a standard, graduated, or stepwise approach for managing
constipation; however, only % of respondents reported that
referring physicians used a graduated or stepwise approach
in managing patients with constipation. Most respondents
reported that patients (%) and referring physicians (%)
were reluctant to move from over-the-counter (OTC) thera-
pies to prescription medications.
Among the six therapeutic options to manage consti-
pation, the respondents selected osmotic laxatives and bre
supplements/bulking agents as the rst-line (ranked  or  of
question (4) in this survey) treatment of both CIC and IBS-
C (Figure ). Stool soeners were shown to be statistically
the least satisfying treatment option for patients with CIC
(Figure (a), 𝑝 = 0.0002) when analyzing the responses from
those who rated each treatment option as “” (question (6)
of the survey). When ratings of “” and “” (question (6)

Canadian Journal of Gastroenterology and Hepatology 
Other
Prokinetic (5-HT4 agonist)
Osmotic laxatives
Stool soeners
Stimulant laxatives
5 1015202530350
(%)
Prosecretory agent
(GCC agonist)
Fibre supplement/bulking
agent
Inadequate bre intake (n=54)
CIC, slow transit (n=54)
CIC, functional outlet obstruction (n=54)
IBS (n=54)
F : Types of treatment patients would ideally receive based
on the type of chronic constipation (the Appendix: Question (4)).
Osmotic laxatives were ranked as rst-line treatment for both CIC
and IBS-C, followed by bre supplements/bulking agents being
second-line treatment for CIC and GCC agonist being second-line
treatment for IBS-C. (CIC:chronic idiopathic constipation; IBS-C:
constipation-predominant irritable bowel syndrome; GCC:guanylyl
cyclase C).
of the survey) were grouped for analysis, stimulant laxatives
werealsofoundtobeanunsatisfyingtreatmentoptionfor
CIC (𝑝 = 0.0002). On the other hand, GCC agonist (𝑝<
0.0001), osmotic laxatives (𝑝 < 0.0001), -HT agonist
(𝑝 = 0.0003), and bre supplements/bulking agents (𝑝=
0.0069) were considered to be satisfying treatments for CIC.
For patients with IBS-C, respondents identied both stool
soeners and stimulant laxatives as signicantly unsatisfying
treatment options (Figure (b), 𝑝 < 0.0001 and 𝑝 = 0.038,
resp.).SimilartothemanagementofCIC,GCCagonist(𝑝<
0.0001), osmotic laxatives (𝑝 < 0.0001), -HT agonist (𝑝=
0.003), and bre supplements/bulking agents (𝑝 = 0.004)
were considered to be satisfying treatments for IBS-C, with
GCC agonist being the most satisfying treatment option (𝑝=
0.03 when ratings of “” were analyzed).
Abdominal pain/bloating were ranked as being the most
burdensome symptoms that aect QoL in patients of CIC
and IBS-C (% and %, Figure ). Our survey indicated
that the respondents reported that their patients least likely
complained of abdominal pain/bloating while using GCC
agonist, suggesting that this agent may be the most eec-
tive to alleviate patients with constipation and abdominal
pain/bloating and least likely to cause these symptoms as side
eects (Figure ).
3.2.AwarenessandPerceptionoftheUsefulnessofACGGuide-
lines. Despite the majority of respondents (%) being aware
of the recent ACG guideline for managing CIC and IBS-C,
only half of the respondents (%, somewhat helpful, %,
very helpful) found the guideline helpful to prioritize the use
of available treatment options. Hence, most of them (%)
expressed great interest in having a treatment algorithm that
wouldbeapplicabletoCanadianpractice.
4. Discussion
Although eorts were made to increase response rate by
using hardcopy survey and online survey tool with reminders
being sent to encourage participation, the response rate
was only % (𝑛=55), which can be a limitation of
generalizability of this study. is may reect the lack of
interest and/or knowledge in this eld of gastroenterology
although this aspect is beyond the scope of this survey.
Nevertheless, we believe that the results of this survey still
provide useful information on gastroenterologists’ practice
in the management of IBS-C and CIC in Canada since we
speculatethatthosewhorespondedtothissurveywerelikely
to be more familiar with the conditions.
eresultsofthissurveyindicatethatmanyspecialists
believe that referring physicians might not follow a similar
stepwise approach to the management of constipation that
many specialists use. is may cause unsatisfactory treatment
outcomes in some patients, resulting in unnecessary referrals.
In addition, results suggest there is the perception that
both patients and/or referring physicians may be reluctant
to move from OTC therapies to prescription agents such
as prucalopride or linaclotide, when the former failed to
provide symptomatic relief. is could be due to a number
of factors, including ease of access and limited reimburse-
ment for prescription medications, prescriber experience and
knowledge of newer treatment options, perceived severity of
taking prescription medications, and dierence in treatment
schedule of OTC versus prescription medications. Responses
collected from this survey suggest that there is a need to
provide education not only to specialists but also to referring
physicians and patients.
Although the Rome diagnostic criteria distinguish IBS-C
from CIC, in clinical practice, these conditions are a spectrum
of illnesses with overlapping symptoms and interchangeable
diagnosis over time in the same patient [, ]. is clinical
observation is consistent with our survey illustrating that
abdominal pain/bloating being most frequently reported
by the respondents to be the most burdensome symptoms
that aect their patients’ QoL in both CIC and IBS-C
(Figure ). e respondents also reported that when GCC
agonist was used to treat their patients with constipation,
their patients least likely complained of abdominal pain and
bloating (Figure ). We believe that this is the underlying
reason the respondents nd using GCC agonist the most
satisfying in treating their patients with CIC and IBS-C
(Figure ). is survey’s outcome was supported by clinical
trial observations that GCC agonist, linaclotide, improves
both bowel movement frequency and abdominal pain [–
].

 Canadian Journal of Gastroenterology and Hepatology
Satised
Neutral
Not satised
10 20 30 40 50 60 70 80 90 1000
(%)
Stimulant laxatives
(n=54)
Stool soeners
(n=54)
Osmotic laxatives
(n=54)
Prokinetic
(5-HT4agonist) (n=49)
Fibre supplement/
bulking agent (n=54)
Prosecretory agent
(GCC agonist) (n=50)
(a)
Satised
Neutral
Not satised
10 20 30 40 50 60 70 80 90 1000
(%)
Stimulant laxatives
(n=53)
Stool soeners
(n=52)
Osmotic laxatives
(n=51)
Prokinetic
(5-HT4agonist) (n=48)
Fibre supplement/
bulking agent (n=51)
Prosecretory agent
(GCC agonist) (n=47)
(b)
F : (a) Respondents’ satisfaction with treatment options for managing patients with CIC. Stool soeners and stimulant laxatives
(𝑝 = 0.0002) were found to be unsatisfying treatments for CIC compared to other options. On the other hand, GCC agonist (𝑝 < 0.0001),
osmotic laxatives (𝑝 < 0.0001), -HT agonist (𝑝 = 0.0003), and bre supplements/bulking agents (𝑝 = 0.0069)wereconsideredtobe
satisfying treatments for CIC among the treatment options being surveyed. (CIC:chronic idiopathic constipation; GCC:guanylyl cyclase C.)
(b) Respondents’ satisfaction with treatment options for managing patients with IBS-C. Both stool soeners (𝑝 < 0.0001) and stimulant
laxatives (𝑝 = 0.038) were unsatisfying treatments for IBS-C compared to other options, whereas GCC agonist (𝑝 < 0.0001), osmotic laxatives
(𝑝 < 0.0001), -HT agonist (𝑝 = 0.003), and bre supplements/bulking agents (𝑝 = 0.004) were considered to be satisfying treatments for
IBS-C among the treatment options being surveyed. (IBS-C:constipation-predominant irritable bowel syndrome; GCC:guanylyl cyclase C).
Abdominal pain/bloating
Straining during bowel movements
Sensation of incomplete evacuation
Sensation of anorectal obstruction/blockage
Infrequent stools
5 1015202530350
(%)
CIC (n=54)
IBS-C (n=54)
F : Respondents’ perceptions of symptoms that most aect patients’ quality of life based on the type of constipation. Abdominal
pain/bloating was ranked as being the most burdensome symptom in both CIC (%) and IBS-C (%). (CIC:chronic idiopathic constipation;
IBS-C:constipation-predominant irritable bowel syndrome).
Due to the overall negative impact of CIC and IBS-C
on the patients’ QoL and the health care system, practice
guidelines had been developed. While the recent ACG and
AGA guidelines for CIC and IBS-C management are avail-
able, there are limitations of applying these guidelines directly
in Canadian clinical practice; for example, availability and
accessibility of drugs are dierent between the United States
and Canada. In addition, physician adherence to guidelines is
another limitation of translating these guidelines in clinical
practice. Literature suggests that physician adherence to

Canadian Journal of Gastroenterology and Hepatology 
Abdominal pain/bloating
Stimulant laxatives (n=40)
Stool soeners (n=42)
Osmotic laxatives (n=40)
Prokinetic (5-HT4agonist) (n=38)
Fibre supplement/bulking agent (n=49)
Prosecretory agent (GCC agonist) (n=31)
20 40 60 80 1000
(%)
F : Respondents’ perceptions of symptoms that patients most oen complain about while being on various therapy options. For
abdominal pain/bloating, which was being identied as the symptom that most aects patients’ quality of life in both CIC and IBS-C,
patients who were prescribed GCC agonist appeared to be least likely to report abdominal pain/bloating, suggesting that this agent may be the
most eective to alleviate patients with constipation and abdominal pain/bloating. (CIC:chronic idiopathic constipation; IBS-C:constipation-
predominant irritable bowel syndrome; GCC:guanylyl cyclase C).
guidelines is oen quite inadequate [–]. Adherence can
be restricted by several factors, including the length and
complexity of guideline content, the presence of multiple
guidelines (in dierent versions or from dierent groups),
and limited access to the guidelines in a clinical practice
setting [].
Another practical limitation of guidelines, such as the
ACG[]andtheAGA[,]guidelines,isthattheydo
not prioritize the use of recommended agents to achieve
optimal patient outcomes since head-to-head evaluation of
treatment eects of various agents is not usually available.
Hence, it will rely on real-world treating physician experience
to choose which agent to use when various agents receive
strong recommendation. e feedback gathered from the
needs assessment survey clearly indicates that a Canadian-
centered and evidence- and experience-based algorithm that
guides physicians to select the appropriate treatment options
is needed. Based on the responses from this survey, available
evidences, and experience of the authors, we develop an algo-
rithmtohelpphysicianstomanagepatientswithconstipation
(Figure ).
4.1. Development of the Treatment Algorithm
4.1.1. History and Physical Examination. Athoroughhis-
tory and physical examination including digital anorectal
examination (DARE) are important in identifying secondary
causes such as medication-induced constipation (e.g., opi-
oids, calcium-channel blockers, and anticholinergics) and
other underlying medical comorbidities (e.g., diabetes, con-
nectivetissuediseases,andneurologicaldiseases).Ifalarming
features (such as new onset of symptoms aer  years of
age, rectal bleeding, nocturnal symptoms, signicant weight
loss, fever, and anemia) or abnormal physical examination are
identied, the patient should be referred to a specialist for
further assessment to rule out more ominous etiology, such
as malignancy.
e purpose of performing a careful DARE is to identify
patients who may have dyssynergic defecation (DD) as an
etiology of their constipation because management may
involve further investigation such as anorectal manometry
(ARM) or defecography. However, a careful DARE was
found to be accurate with a positive predictive value of
over % compared to ARM in two independent population
cohorts presented with constipation [, ]. When DD is
identied by DARE in patients presented with constipation,
a referral to pelvic health physiotherapists for biofeedback is
recommended to optimize treatment outcomes in addition to
a regular bowel regimen [].
A thorough history and physical examination not only
allow the physicians to assess alarming features or secondary
causes but also allow the physician to establish a therapeutic
relationshipwiththepatient.iswillprovideanopportunity
for the physician to address the patient’s concerns and to
educate the patient about what is being considered to be
normal bowel movements, including the natural variation of
bowel functions and the range of normal stool frequency, as
well as set realistic treatment goals for each individual patient.
Dietary and lifestyle modications (i.e., optimizing dietary
bre and uid intake and encouraging regular physical
activity) should rst be considered as initial management.
Because of the lack of harmful eect of lifestyle and dietary
modication, it is widely accepted and recommended by
experts as rst-line therapy; despite the lack of strong evi-
dence that these measures improve constipation, they have

 Canadian Journal of Gastroenterology and Hepatology
e.g., milk of magnesia, lactulose, or PEG
supplements
Trial at a reasonable dose of 4–8 weeks prior
to reassessment of maintenance or
escalation to step-up therapies
Additional agents: Additional therapy:
Pharmacological
e.g., TCA, SSRI, and
SNRL antispasmodic
Nonpharmacological
e.g., meditation,
relaxation, and hypnosis
Fibre supplements Osmotic laxatives Prosecretory agents
e.g., linaclotide
Specialist assessment for
consideration of anorectal
manometry, defecography, and
biofeedback therapy
Eight- to twelve-week trial prior to reassessment
for maintenance or consideration of referral for
specialist assessment
Prosecretory or prokinetic
agents
Unsatisfactory response or intolerant to side eects
Specialist assessment recommended (refer)
(1) Glycerine suppository
(2) Stimulant laxatives (e.g., bisacodyl)
(3) Enema
Rescue therapy
Constipation
symptoms
predominant
Function al
abdominal pain
predominant
Type of constipation?
Lifestyle modications (e.g., dietary bre, uid, and exercise)
Inadequate bre intake CIC, slow transit IBS-C Pelvic oor dyssynergic
defecation
History and physical examination including careful perineal/rectal examination
Assess alarm features Optimize management of secondary causes
Alarm features identied No alarm features identied Constipation persists
Specialist assessment
recommended (refer)
Patient education and management of expectations
Assess for complex or complicating features
Chronic Constipation Management Algorithm
e.g., linaclotide or prucalopride
Options as in slow
(e.g., stimulant,
osmotic laxative)
transit∗
titrate to ecacy and tolerability +/−bre
F : Management algorithm for chronic constipation. e priority usage of each therapeutic option depends on patients’ tolerability and
aordability. ∗𝑇ℎ𝑒𝑟𝑒 has been no evidence to support the use of prucalopride in patients with IBS-C. (IBS-C:constipation-predominant irritable
bowel syndrome).
been shown to improve overall QoL and IBS symptoms
severity [–].
4.1.2. Treatment Recommendations Based on
Subtypes of Constipation
(1) Inadequate Fibre Intake. e recommended daily bre
intake is – g []. Fibre supplement helps increase
stool weight and improve stool consistency [] in order
to decrease stool transit time []. In patients with low
breintakebasedondietaryhistory,itislogicaltoadd
bre supplements. Soluble, such as psyllium, is preferable
overinsolublebrebecauseofthelowerpropensitytocause
associated abdominal symptoms (e.g., bloating or abdominal
pain); hence it is better tolerated by most patients []. e
recommended daily bre supplement intake is generally up
to  g per day []; the target consumption can be achieved
with gradual incremental increases (e.g.,  g/day increment
per week) to avoid side eects such as bloating and atulence.
(2) Chronic Idiopathic Constipation and Slow-Transit Consti-
pation. A thorough history and digital rectal examination
alongwiththeBristolStoolChartisfrequentlyadequateto
diagnose patients with slow-transit constipation. Type  or
 Bristol stool consistency correlates with prolonged colonic
transit time []. Although sitz marker colonic transit study
can be helpful, it is not widely accessible.
In patients with slow-transit constipation, osmotic lax-
atives are recommended as the rst-line pharmacological
agents to be used because of their eectiveness, accessibility,
and aordability. Milk of magnesia, lactulose, and PEG are
themostcommonlyusedosmoticlaxativesinCanada.Both
lactulose and PEG had randomized-controlled trials (RCTs)
to support their use [–] while milk of magnesia was
based on expert opinions and clinical experience [, ].
Milk of magnesia should not be used in patients with renal
impairment because of its renal excretion. In general, PEG
causes less bloating and atulence compared to lactulose; thus
it may result in better tolerability and compliance by patients.
If patients experience no improvement with their con-
stipation aer using osmotic laxatives, GCC agonist (lina-
clotide) or prokinetic agent (prucalopride) is recommended
as the second-line agent for regular use. Rescue therapy (i.e.,

Canadian Journal of Gastroenterology and Hepatology 
T : Current recommended dosages of pharmacological agents for the treatment of constipation.
Typ e Age nt Do s e
Prosecretory agent Linaclotide  𝜇g oral daily (IBS-C);  𝜇goral
daily (CIC)
Fibre supplement Psyllium
 g daily or as tolerated; incremental
increases of -  g/week to achieve target
consumption
Prokinetic agent Prucalopride
mgoraldaily;dosereducestomgoral
daily in patients ≥ years of age or renal
insuciency with creatinine clearance
≤ mL/min
Osmotic laxative
Lactulose – mL oral twice daily as needed
PEG   g/day as needed
Magnesium hydroxide∗– mL ( mg/mL) oral daily as
needed
Stimulant laxative
Sodium picosulfate  mg once daily
Senna .–. mg once daily
Bisacodyl – mg once dai ly
∗Avo id in patients with chronic renal insuciency.
glycerine suppository, stimulant laxatives, and enema) can
beaddedasadjuvanttherapyforoccasionaluse.Suppository
and enema are sometimes dicult for patients to administer.
ere is clinical opinion that stimulant laxatives could cause
dependency and cathartic colon if used regularly although
direct evidence to support this claim is unavailable.
An adequate trial of osmotic laxative use before stepping
up to the second-line agents varies depending on the ability to
provide follow-up in clinical practice. We recommend that if
a patient does not achieve a satisfactory response by  weeks,
therapy should be advanced to second-line agents such as
prucalopride or linaclotide. Eectiveness of linaclotide and
prucalopride in treating constipation has been proven in mul-
tiple placebo-controlled RCTs [–, –]. e commonly
reported side eect of linaclotide is diarrhea. In comparison,
prucalopride causes headache, nausea, abdominal pain, and
diarrhea in –% treated patients. is side eect prole
likely reects in the result of our survey that the respondents
found linaclotide most satisfactory in treating their patients
with constipation. Furthermore, in Canada, prucalopride is
only approved for use in woman with CIC; linaclotide is
approved for adults with CIC.
Stool soeners are not included in our management
algorithm because of weak evidence in supporting their use
[, ]. In fact, a multicenter double-blinded RCT involving
 patients for two weeks revealed inferiority of sodium
docusate compared to psyllium at improving stool frequency
[]. Probiotics are not included in the algorithm currently
due to insucient evidence to support their use [].
(3) IBS-C. A hallmark feature that distinguishes patients
diagnosed with IBS-C from CIC is the presence of associated
functional abdominal symptoms, namely, abdominal pain
and bloating. is has been consistently demonstrated in a
previous Canadian population study [] and in our current
survey. erefore, treatment agents that alleviate both consti-
pation and the associated debilitating functional abdominal
symptom would be preferable.
A GCC agonist, linaclotide, has been shown to improve
satisfactory complete spontaneous bowel movement fre-
quency and decrease associated abdominal pain [–]. Our
survey respondents also identied GCC agonist to be the
most satisfying in treating their patients with IBS-C. Hence,
the authors recommend linaclotide to be used as the rst-line
pharmacological agent in patients with IBS-C. e dosage of
linaclotide indicated for IBS-C is 𝜇gdailywhereasfor
CIC is  𝜇g daily (Table ).
Depending on the treatment response, supplemental
therapy such as stimulant laxatives and osmotic laxatives can
be used in patients requiring further treatment for consti-
pation, or neuropathic agents (selective serotonin reuptake
inhibitors, serotonin-norepinephrine reuptake inhibitors, tri-
cyclic antidepressants, or antispasmodics) in patients requir-
ing additional therapy for abdominal pain. It is worth not-
ing that tricyclic antidepressants and antispasmodics oen
worsen constipation. Nonpharmacological therapy such as
meditation, relaxation, or hypnosis has been shown to
improve functional abdominal symptoms in patients with IBS
[]. Patients who do not respond or are intolerable to the
treatment options outlined in the algorithm are suggested to
be referred to specialized centers for further assessment.
5. Conclusion
Our Canadian survey suggests that management strategies
for CIC and IBS-C among physicians are heterogeneous,
which can result in dissatisfaction in treatment response from
both patients and physicians. A management algorithm for

 Canadian Journal of Gastroenterology and Hepatology
chronic constipation specically developed to apply in Cana-
dian practice will help in optimizing treatment outcomes for
patients suering from these functional GI disorders.
Appendix
Chronic Constipation Questionnaire
How would you describe your current work environ-
ment?
◻Academic
◻Community
◻Other: —
What is your current speciality?
◻General Surgery
◻GI specialist
◻Internal medicine
◻Family Practitioner
◻Other: —
Please identify any other role you have (select all that
apply)
◻Educator
◻Researcher
◻Administrator
◻Other: —
() How many patients with chronic constipation do you
see on a monthly basis?
◻None
◻<
◻–
◻–
◻–
◻–
◻+
() Do you generally follow a standard, graduated or
stepwise approach to the management of all patients
with constipation?
◻Yes
◻No
() In your experience, do you think that referring
physicians follow a standard, graduated or stepwise
approach to the management of patients with consti-
pation?
◻Yes
◻No
() Based on the type of chronic constipation, please
mark the order in which the patient would ideally
receive the following categories or treatment? Please
orderfrom1–6(1=rstchoice,6=lastchoice)
Inadequate bre intake
Stimulant laxatives ...
Stool soeners ...
Osmotic laxatives ...
Prokinetic (-HT agonist) ...
Fibre supplement/bulking agent ...
Pro-secretory Agent (GCC agonist) ...
Other agents ...
CIC, Slow Transit
Stimulant laxatives ...
Stool soeners ...
Osmotic laxatives ...
Prokinetic (-HT agonist) ...
Fibre supplement/bulking agent ...
Pro-secretory Agent (GCC agonist) ...
Other agents ...
CIC, Functional Outlet Obstruction (ie. Pelvic
oor dysfunction)
Stimulant laxatives ...
Stool soeners ...
Osmotic laxatives ...
Prokinetic (-HT agonist) ...
Fibre supplement/bulking agent ...
Pro-secretory Agent (GCC agonist) ...
Other agents ...
IBS-C
Stimulant laxatives ...
Stool soeners ...
Osmotic laxatives ...
Prokinetic (-HT agonist) ...
Fibre supplement/bulking agent ...
Pro-secretory Agent (GCC agonist) ...
Other agents ...
() Doyoufeelthereisreluctancetomovefromover-the-
counter therapies to prescription agents from:
(A) Patients
◻Yes
◻No
(B) Referring Physicians
◻Yes
◻No
()Howsatisedareyouwiththefollowingtreatment
options when managing patients with (A) CIC and
(B) IBS-C? ( being not satised,  being neutral, 
being very satised)

Canadian Journal of Gastroenterology and Hepatology 
Stimulant Laxatives
◻
◻
◻
◻
◻
Stool Soeners
◻
◻
◻
◻
◻
Osmotic Laxatives
◻
◻
◻
◻
◻
Prokinetic (-HT agonist)
◻
◻
◻
◻
◻
Fibre supplement/bulking agent
◻
◻
◻
◻
◻
Pro-secretory Agent (GCC agonist)
◻
◻
◻
◻
◻
()Basedonthetypeofconstipation,pleaseidentify
which symptoms you feel most aect your patients
quality of life? (Order symptoms from –,  being the
most burdensome,  being the least)
CIC
Abdominal pain/bloating ...
Straining during bowel movements ...
Sensation of incomplete evacuation ...
Sensation of anorectal obstruction/block-
age ...
Infrequent stools ...
IBS-C
Abdominal pain/bloating ...
Straining during bowel movements ...
Sensation of incomplete evacuation ...
Sensation of anorectal obstruction/block-
age ...
Infrequent stools ...
() In your experience, which symptoms (if any) do
patients most oen complain about while on the
following therapy options? (Please select all that
apply)
Stimulant Laxatives
Abdominal pain/bloating ...
Straining during bowel movements ...
Sensation of incomplete evacuation ...
Sensation of anorectal obstruction/block-
age ...
Infrequent stools ...
Stool Soeners
Abdominal pain/bloating ...
Straining during bowel movements ...
Sensation of incomplete evacuation ...
Sensation of anorectal obstruction/block-
age ...
Infrequent stools ...
Osmotic Laxatives
Abdominal pain/bloating ...
Straining during bowel movements ...
Sensation of incomplete evacuation ...
Sensation of anorectal obstruction/block-
age ...
Infrequent stools ...
Prokinetic (-HT agonist)
Abdominal pain/bloating ...
Straining during bowel movements ...
Sensation of incomplete evacuation ...
Sensation of anorectal obstruction/block-
age ...
Infrequent stools ...
Fibre supplement/bulking agent
Abdominal pain/bloating ...
Straining during bowel movements ...
Sensation of incomplete evacuation ...
Sensation of anorectal obstruction/block-
age ...
Infrequent stools ...
Pro-secretory Agent (GCC agonist)
Abdominal pain/bloating ...
Straining during bowel movements ...
Sensation of incomplete evacuation ...
Sensation of anorectal obstruction/block-
age ...
Infrequent stools ...
() Are you aware of the new ACG  recommen-
dations on the management of IBS-C and Chronic-
Idiopathic Constipation from ?

 Canadian Journal of Gastroenterology and Hepatology
◻Yes
◻No
(a) If yes, how useful are the ACG guidelines in
helping you prioritize how available agents are
used? ( being not useful,  being neutral, and 
being very useful)
◻
◻
◻
◻
◻
(b) How valuable do you feel an evidence based
treatment algorithm that translates the ACG
guidelines into Canadian clinical practice would
be? ( being not valuable,  being neutral,  being
very valuable)
◻
◻
◻
◻
◻
Competing Interests
Dr. Yvonne Tse has received honorarium for participation
in advisory boards from AbbVie. Dr. David Armstrong
has received research funding from AbbVie; honoraria for
participation in advisory boards and/or speaking at educa-
tional events from AbbVie, Allergan, Cubist, Ferring, Hos-
pira, Janssen, Lupin, Pendopharm, Pentax, Pzer, Shire, and
Takeda; sponsorship for educational events from AbbVie,
Allergan, Boston Scientic, Cook Medical, Ferring, Hospira,
Janssen, Lupin, Olympus, Pendopharm, Shire, and Takeda.
Dr. Christopher Andrews has received research funding
from Janssen and Allergan and honoraria from Allergan,
Pendopharm, Lupin, and AbbVie. Dr. Alain Bitton has
received honorarium for participation in advisory boards
from Allergan. Dr. Brian Bressler has received research
funding from AbbVie, Amgen, Takeda, BMS, Genentech,
Janssen, BI, GSK, Redhill Biopharm, Celgene, and Merck;
honoraria for participation in advisory boards and/or speak-
ing at educational events from AbbVie, Janssen, Takeda,
Shire, Pendopharm, Ferring, Pzer, Amgen, and Merck;
honoraria for providing consulting service from Genentech,
Pendopharm, and Allergan. Dr. John Marshall has received
honoraria for participation in speaking at educational events
from AbbVie, Allergan, Ferring, Janssen, Procter & Gamble,
Shire, and Takeda and honoraria for providing consulting
service from AbbVie, Allergan, Astra-Zeneca, Boehringer-
Ingelheim, Celgene, Celltrion, Ferring, Hospira, Janssen,
Merck, Pzer, Pharmascience, Procter & Gamble, Shire, and
Takeda. Dr. Louis Liu has received honoraria for participation
in advisory boards and/or speaking at educational events
from Takeda, AbbVie, Allergan, and Lupin and honorarium
for providing consulting service from Allergan.
Acknowledgments
e authors thank Converge and CARE for providing man-
agement, analytic, and research funds in support of this
Canadian National Survey project.
References
[] P. D. R. Higgins and J. F. Johanson, “Epidemiology of constipa-
tion in North America: a systematic review,” American Journal
of Gastroenterology,vol.,no.,pp.–,.
[] R. M. Lovell and A. C. Ford, “Global prevalence of and risk
factors for irritable bowel syndrome: a meta-analysis,” Clinical
Gastroe nterology and Hepatology,vol.,no.,pp.–,.
[] e Canadian Digestive Health Foundation, Irritable Bowel
Syndrome (IBS), e Canadian Digestive Health Foundation,
Oakville, Canada, .
[] J.J.Heidelbaugh,M.Stelwagon,S.A.Miller,E.P.Shea,andW.
D. Chey, “e spectrum of constipation-predominant irritable
bowel syndrome and chronic idiopathic constipation: US sur-
vey assessing symptoms, care seeking, and disease burden,” e
AmericanJournalofGastroenterology,vol.,no.,pp.–
, .
[] E. J. Irvine, S. Ferrazzi, P. Pare, W. G. ompson, and L. Rance,
“Health-related quality of life in functional GI disorders: focus
on constipation and resource utilization,” e American Journal
of Gastroenterology,vol.,no.,pp.–,.
[] P. Par´
e,J.Gray,S.Lametal.,“Health-relatedqualityoflife,work
productivity, and health care resource utilization of subjects
with irritable bowel syndrome: baseline results from logic
(longitudinal outcomes study of gastrointestinal symptoms in
Canada), a naturalistic study,” Clinical erapeutics,vol.,no.
, pp. –, .
[] R.K.Wong,O.S.Palsson,M.J.Turneretal.,“Inabilityofthe
Rome III criteria to distinguish functional constipation from
constipation-subtype irritable bowel syndrome,” e American
Journal of Gastroenterology,vol.,no.,pp.–,.
[]O.S.Palsson,J.Baggish,andW.E.Whitehead,“Episodic
nature of symptoms in irritable bowel syndrome,” e American
journal of gastroenterology,vol.,no.,pp.–,.
[] A.C.Ford,P.Moayyedi,B.E.Lacyetal.,“Americancollegeof
gastroenterology monograph on the management of irritable
bowel syndrome and chronic idiopathic constipation,” Ameri-
can Journal of Gastroenterology,vol.,no.,pp.S–S,.
[]A.E.Bharucha,S.D.Dorn,A.Lembo,andA.Pressman,
“American gastroenterological association medical position
statement on constipation,” Gastroenterology,vol.,no.,pp.
–, .
[] D. S. Weinberg, W. Smalley, J. J. Heidelbaugh, and S. Sultan,
“American gastroenterological association institute guideline
on the pharmacological management of irritable bowel syn-
drome,” Gastroenterology,vol.,no.,pp.–,.
[]W.D.Chey,A.J.Lembo,B.J.Lavinsetal.,“Linaclotide
for irritable bowel syndrome with constipation: a -week,
randomized, double-blind, placebo-controlled trial to evaluate
ecacy and safety,” American Journal of Gastroenterology,vol.
, no. , pp. –, .
[] J. M. Johnston, C. B. Kurtz, J. E. MacDougall et al., “Linaclotide
improves abdominal pain and bowel habits in a phase IIb study
of patients with irritable bowel syndrome with constipation,”
Gastroenterology, vol. , no. , pp. .e–.e, .

Canadian Journal of Gastroenterology and Hepatology 
[] S. Rao, A. J. Lembo, S. J. Shi et al., “A -week, randomized,
controlled trial with a -week randomized withdrawal period
to evaluate the ecacy and safety of linaclotide in irritable
bowel syndrome with constipation,” e American Journal of
Gastroenterology,vol.,no.,pp.–,.
[] T. Foitzik and E. Klar, “(Non-) compliance with guidelines for
the management of severe acute pancreatitis among German
surgeons,” Pancreatolog y,vol.,no.,pp.–,.
[] J. A. Greenberg, J. Hsu, M. Bawazeer et al., “Compliance
with evidence-based guidelines in acute pancreatitis: an audit
of practices in university of Toronto hospitals,” Journal of
Gastrointestinal Surgery,vol.,no.,pp.–,.
[] A. C. Vlada, B. Schmit, A. Perry, J. G. Trevino, K. E. Behrns,
and S. J. Hughes, “Failure to follow evidence-based best practice
guidelines in the treatment of severe acute pancreatitis,” HPB,
vol.,no.,pp.–,.
[]J.Carthey,S.Walker,V.Deelchand,C.Vincent,andW.H.
Griths, “Breaking the rules: understanding non-compliance
with policies and guidelines,” British Medical Journal,vol.,
no.,ArticleIDd,.
[] K.Tantiphlachiva,P.Rao,A.Attaluri,andS.S.C.Rao,“Digital
rectal examination is a useful tool for identifying patients with
dyssynergia,” Clinical Gastroenterology and Hepatology,vol.,
no. , pp. –, .
[] J. S. Soh, H. J. Lee, K. W. Jung et al., “e diagnostic value
of a digital rectal examination compared with high-resolution
anorectal manometry in patients with chronic constipation and
fecal incontinence,” American Journal of Gastroenterology,vol.
, no. , pp. –, .
[] S. S. C. R ao, M. A. Benninga, A. E. Bharucha, G. Chiarioni, C. Di
Lorenzo, and W. E. Whitehead, “ANMS-ESNM position paper
and consensus guidelines on biofeedback therapy for anorectal
disorders,” Neurogastroenterology & Motility,vol.,no.,pp.
–, .
[] L. W. Liu, “Chronic constipation: current treatment options,”
Canadian Journal of Gastroenterology, vol. , supplement B, pp.
B–B, .
[] P. Pare, R. Bridges, M. C. Champion et al., “Recommendations
on chronic constipation (including constipation associated with
irritable bowel syndrome) treatment,” Canadian Journal of
Gastroenterology,vol.,supplement,pp.B–B,.
[] M. Camilleri and A. E. Bharucha, “Behavioural and new phar-
macological treatments for constipation: getting the balance
right,” Gut,vol.,no.,pp.–,.
[] A.V.Emmanuel,J.Tack,E.M.Quigley,andN.J.Talley,“Phar-
macological management of constipation,” Neurogastroenterol-
ogy and Motility,vol.,no.,pp.–,.
[] e Canadian Digestive Health Foundation, Fibre Fusion
Resource Guide, e Canadian Digestive Health Foundation,
Oakville, Canada, .
[] W. Ashraf, F. Park, J. Lof, and E. M. M. Quigley, “Eects of
psyllium therapy on stool characteristics, colon transit and
anorectal function in chronic idiopathic constipation,” Alimen-
tary Pharmacology & erapeutics,vol.,no.,pp.–,
.
[] L. J. Cheskin, N. Kamal, M. D. Crowell, M. M. Schuster, and W.
E. Whitehead, “Mechanisms of constipation in older persons
andeectsofbercomparedwithplacebo,”Journal of the
American Geriatrics Society,vol.,no.,pp.–,.
[] S. J. Lewis and K. W. Heaton, “Stool form scale as a useful guide
to intestinal transit time,” Scandinavian Journal of Gastroen-
terology,vol.,no.,pp.–,.
[] A. Wesselius-De Casparis, S. Braadbaart, G. E. Bergh-Bohlken,
and M. Mimica, “Treatment of chronic constipation with
lactulose syrup: results of a double-blind study,” Gut,vol.,no.
,pp.–,.
[] J. F. Sanders, “Lactulose syrup assessed in a double-blind
study of elderly constipated patients,” Journal of the American
Geriatrics Society,vol.,no.,pp.–,.
[] M. D. Freedman, H. J. Schwartz, R. Roby, and S. Fleisher,
“Tolerance and ecacy of polyethylene glycol /electrolyte
solution versus lactulose in relieving opiate induced consti-
pation: a double-blinded placebo-controlled trial,” Jour nal of
Clinical Pharmacology,vol.,no.,pp.–,.
[] Y.C.Baldonedo,E.Lugo,A.A.Uzcategui,M.Guelrud,and
J. Skornicki, “Evaluation and use of polyethylene glycol in
constipated patients,” GEN,vol.,pp.–,.
[] E. Corazziari, D. Badiali, F. I. Habib et al., “Small volume
isosmotic polyethylene glycol electrolyte balanced solution
(PMF-) in treatment of chronic nonorganic constipation,”
Digestive Diseases and Sciences,vol.,no.,pp.–,
.
[] E. Corazziari, D. Badiali, G. Bazzocchi et al., “Long term
ecacy, safety, and tolerabilitity of low daily doses of isosmotic
polyethylene glycol electrolyte balanced solution (PMF-) in
the treatment of functional chronic constipation,” Gut,vol.,
no. , pp. –, .
[] J. A. DiPalma, M. V. B. Cleveland, J. McGowan, and J. L.
Herrera, “A randomized, multicenter, placebo-controlled trial
of polyethylene glycol laxative for chronic treatment of chronic
constipation,” American Journal of Gastroenterology,vol.,
no.,pp.–,.
[] J. A. DiPalma, P. H. DeRidder, R. C. Orlando, B. E. Kolts, and M.
B. Cleveland, “A randomized, placebo-controlled, multicenter
study of the safety and ecacy of a new polyethylene glycol
laxative,” e American Journal of Gastroenterology,vol.,no.
,pp.–,.
[] M. Camilleri, R. Kerstens, A. Rykx, and L. Vandeplassche,
“A placebo-controlled trial of prucalopride for severe chronic
constipation,” New England Journal of Medicine,vol.,no.,
pp. –, .
[] E. M. M. Quigley, L. Vandeplassche, R. Kerstens, and J.
Ausma, “Clinical trial: e ecacy, impact on quality of life,
and safety and tolerability of prucalopride in severe chronic
constipation—a -week, randomized, double-blind, placebo-
controlled study,” Alimentary Pharmacology and erapeutics,
vol.,no.,pp.–,.
[] J. Tack, M. van Outryve, G. Beyens, R. Kerstens, and L. Van-
deplassche, “Prucalopride (Resolor) in the treatment of severe
chronic constipation in patients dissatised with laxatives,” Gut,
vol.,no.,pp.–,.
[] S. C. C astle, M. Cantrell, D. S. Israel, and M. J. Samuelson, “C on-
stipation prevention: empiric use of stool soeners questioned,”
Geriatrics, vol. , no. , pp. –, .
[] J. W. Mcrorie, B. P. Daggy, J. G. Morel, P. S. Diersing, P. B. Miner,
and M. Robinson, “Psyllium is superior to docusate sodium for
treatment of chronic constipation,” Alimentary Pharmacology
and erapeutics,vol.,no.,pp.–,.
[]A.C.Ford,E.M.M.Quigley,B.E.Lacyetal.,“Eectof
antidepressants and psychological therapies, including hyp-
notherapy, in irritable bowel syndrome: systematic review and
meta-analysis,” e American Journal of Gastroenterology,vol.
, no. , pp. –, .