Document name:
Bowel habit monitoring for
patients prescribed clozapine
(including information on the
management of constipation)
Portfolio
Document type:
Medicines Management
Staff group to whom it
applies:
All prescribers, pharmacy and clinical
staff within the Trust
Distribution:
The whole of the Trust
How to access:
Intranet
Issue date:
Reviewed:
February 2013
Next review:
January 2015
Approved by:
Drug and Therapeutic Sub Committee
Director leads:
Medical Director
Contact for advice:
Med.information@swyt.nhs.uk
Communication
Bowel habit monitoring for patients prescribed clozapine (including information on
the management of constipation).
Background
Gastrointestinal hypomotility is a well recognised side effect of treatment with clozapine,
and can be potentially life threatening. There are also a myriad of other treatments used in
the treatment of both physical and mental health complaints which can affect bowel
function and have an additive effect when combined with clozapine. A recent letter from
the Chief Pharmaceutical officer has highlighted this important area and asks for
monitoring of patients who are at risk of this side effect; the challenge here is that there are
no tools available for monitoring bowel habit in individuals who do not inflammatory bowel
disease.
Clozapine has anticholinergic properties; which may cause constipation due to drying of
gastrointestinal secretions and impairment of smooth muscle neurotransmission.
Clozapine has anti-serotonergic properties which inhibits the initiation of peristalsis and
gastric secretions. Both of these properties are likely to result in a slowing in gastrological
transit time.
Prevalence summary of product characteristics
The SpC for clozapine lists constipation as a very frequent side effect of clozapine, with
reports of 30-60% of patients complaining of this side effect. A recent review estimated
that 3 in 1000 people treated with clozapine will experience life threatening complications
due to constipation.
Definition of chronic constipation
The ROME foundation of Functional Gastrointestinal Disorders defines chronic
constipation as the presence of ≥2 of the following symptoms for the last 3 months, with
symptom onset at least 6 months prior:
 Lumpy or hard stools in more than 25% of defecations
 Straining during more than 25% of defecations
 Sensation of incomplete evacuation in more than25% of defecations
 Sensation of anorectal obstruction / blockage in more than 25% of defecations
 Manual movements to facilitate more than 25% of defecations
 Less than 3 evacuations / week
 Loose stools rarely present without the use of laxatives
 Insufficient criteria for Irritable Bowel Syndrome
To elucidate this information they have designed a tool (See Appendix A)
Criteria for referral
 Unexplained / unplanned weight loss
 Blood in the stool
 Anaemia
 Sudden change in bowel habit after the age of 50
 Significant abdominal pain
 Family history of colon cancer or inflammatory bowel disease
If any of these features are present the service user should be referred to a medical
specialist for further investigations.
Treatment pathway
1. Begin treatment with dietary and lifestyle adjustments (see Food and Nutrition Policy
Appendix 1.7 and 1.8) http://nww.swyt.nhs.uk/docs/Documents/843.pdf
2. Use osmotic laxatives / stool softeners first line
3. Move to stimulant laxatives / suppositories / enemas
4. Referral to a specialist
Choice of agent
There is a lack of evidence to suggest that one laxative is superior to another, however in
cases of slowed gastrointestinal transit time fibre is unlikely to be helpful.
The first line agents should be:
Osmotic laxatives
Movicol, 1 daily (£0.14/day)
Must be given regularly, takes several days for therapeutic effect
Need to ensure the service user is well hydrated for therapeutic effect
Cochrane review shows better tolerated than Lactulose.
Stool softners
Docusate sodium, 100mg bd (0.14/day)
Takes 1-2 days for therapeutic effect
Has mixed stimulant / softener effect
Stimulant laxatives
Senna, 15mg nocte (£0.03/day)
Takes 12hrs for therapeutic effect
NB can be given on symptomatic relief
Suppositories
Glycerin suppositories, 1 to be inserted PRN (£0.04/dose)
NB can be given on symptomatic relief
Enema
Sodium citrate micro enema, 1 to be used as directed PRN (£0.40/dose)
Recommendations
1. All service users on clozapine receive an annual screen using the tool as outlined by
the ROME group.
2. Those service users receiving clozapine and laxatives or anticholinergic drugs receive
more frequent screening depending on need.
3. All service users meeting the criteria for chronic constipation who are prescribed
clozapine are referred for an urgent medical review.
4. All service users reporting constipation but not meeting the criteria for chronic
constipation are managed according to the treatment pathway as outlined above.
References
BNF 62
Tack J, Muller-Lissner S, Stanghellini V, Boeckxstaens G, Kamm MA, Simren M, Galmiche
JP and Fried M. Diagnosis and treatment of chronic constipation – a European
Perspective. Neurogastroenterol Motil: 23: 697-710 (2011)
Lactulose versus Polyethylene glycol for Chronic Constipation (Review). Cochrane
Collaboration (2011)
Taylor RR and Guest JF. The cost-effectiveness of macrogol 3350 compared to lactulose
in the treatment of adults suffering from chronic constipation in the UK. Alimentary
Pharmacology and Therapeutics: 31: 302-312 (2010)
Clozapine and Gastrointestinal obstruction. Letter from the Chief Pharmaceutical Officer.
April 2012.
Flanagen RJ and Ball RY. Gastrointestinal hypomotility: An under-recognised lifethreatening adverse effect of clozapine. Forensic Sci Int: 20 (206): 1-3. (2011)
Appendix A
Constipation Module
1. In the last 3 months, how often
did you have discomfort or pain
anywhere in your abdomen?
2. For women: Did this discomfort
or pain occur only during your
menstrual bleeding and not at other
times?
3. Have you had this discomfort or
pain 6 months or longer?
4. How often did this discomfort or
pain get better or stop after you had
a bowel movement?
5. When this discomfort or pain
started, did you have more frequent
bowel movements?
6. When this discomfort or pain
started, did you have less frequent
bowel movements?
7. When this discomfort or pain
started, were your stools (bowel
movements) looser?
8. When this discomfort or pain
started, how often did you have
harder stools?
9. In the last 3 months, how often
did you have fewer than three
bowel movements (0-2) a week?
10. In the last 3 months, how often
did you have hard or lumpy stools?
11. In the last 3 months, how often
did you strain during bowel
movements?
0 Never →
1 Less than one day a month
2 One day a month
3 Two to three days a month
4 One day a week
5 More than one day a week
6 Every day
0 No
1 Yes
2 Does not apply because I have had
the change in life (menopause) or I
am a male
0 No
1 Yes
0 Never or rarely
1 Sometimes
2 Often
3 Most of the time
4 Always
0 Never or rarely
1 Sometimes
2 Often
3 Most of the time
4 Always
0 Never or rarely
1 Sometimes
2 Often
3 Most of the time
4 Always
0 Never or rarely
1 Sometimes
2 Often
3 Most of the time
4 Always
0 Never or rarely
1 Sometimes
2 Often
3 Most of the time
4 Always
0 Never or rarely
1 Sometimes
2 Often
3 Most of the time
4 Always
0 Never or rarely
1 Sometimes
2 Often
3 Most of the time
4 Always
0 Never or rarely
1 Sometimes
2 Often
3 Most of the time
4 Always
Skip to question 9
12. In the last 3 months, how often
did you have a feeling of incomplete
emptying after bowel movements?
13. In the last 3 months, how often
did you have a sensation that the
stool could not be passed, (i.e.,
blocked), when having a bowel
movement?
14. In the last 3 months, how often
did you press on or around your
bottom or remove stool in order to
complete a bowel movement?
15. In the last 3 months, how often
did you have difficulty relaxing or
letting go to allow the stool to come
out during a bowel movement?
16. Did any of the symptoms of
constipation listed in questions 9-15
above begin more than 6 months
ago?
17. In the last 3 months, how often
did you have loose, mushy or
watery stools?
0 Never or rarely
1 Sometimes
2 Often
3 Most of the time
4 Always
0 Never or rarely
1 Sometimes
2 Often
3 Most of the time
4 Always
0 Never or rarely
1 Sometimes
2 Often
3 Most of the time
4 Always
0 Never or rarely
1 Sometimes
2 Often
3 Most of the time
4 Always
0 No
1 Yes
0 Never or rarely
1 Sometimes
2 Often
3 Most of the time
4 Always
C3. Functional Constipation
Diagnostic criteria*
1. Must include two or more of the following:
a) Straining during at least 25% of
At least often. (question 11>1)
defecations
b) Lumpy or hard stools at least 25% At least often. (question 10>1)
of defecations
c) Sensation of incomplete
At least sometimes. (question 12>0)
evacuation at least 25% of
defecations
d) Sensation of anorectal
At least sometimes. (question 13>0)
obstruction/blockage at least 25% of
defecations
e) Manual maneuvers to facilitate at At least sometimes. (question 14>0)
least 25% of defecations (e.g., digital
evacuation, support of the pelvic
floor)
f) Fewer than three defecations per At least often. (question 9>1)
week
2. Loose stools are rarely present
Loose stools occur never or rarely (question 17=0)
without the use of laxatives.
3. Insufficient criteria for IBS
Diagnostic criteria for IBS not met
* Criteria fulfilled for the last 3
Yes. (question 16=1)
months with symptom onset at least
6 months prior to diagnosis
F3: Functional Defecation Disorders
The diagnostic criteria define FDD solely in terms of laboratory tests. However, the following questions may
identify probable cases who would require further investigation to confirm diagnosis. A response of at least
‘often’ to any of these questions identifies a probable case of FDD:
Straining during bowel movements (question 11>1)
Feeling of incomplete evacuation (question 12>1)
Sensation of blocked stools (question 13>1)
Manual maneuvers to facilitate defecation (question 14>1)
Difficulty relaxing to allow defecation (question 15 >1)
AND criteria for functional constipation are fulfilled
AND onset of constipation symptoms began more than 6 months previously.
Yes. (question 16=1)
Diagnostic Criteria for IBS (Exclusion Criteria for Constipation)*
Recurrent abdominal pain or discomfort** at least 3 days/month in last 3 months associated with two or
more of
criteria #1 - #3 below:
Pain or discomfort at least 2-3 days/month (question 1>2)
For women, does pain occur only during menstrual bleeding? (question 2=0 or 2)
1. Improvement with defecation
Pain or discomfort gets better after BM at least sometimes (question
4>0)
2. Onset associated with a change in Onset of pain or discomfort associated with more stools at least
frequency of stool
sometimes (question 5>0), OR
Onset of pain or discomfort associated with fewer stools at least
sometimes (question 6>0)
3. Onset associated with a change in Onset of pain or discomfort associated with looser stools at least
form (appearance) of stool
sometimes (question 7>0), OR
Onset of pain or discomfort associated with harder stools at least
sometimes (question 8>0)
* Criteria fulfilled for the last 3
Yes. (question 3=1)
months with symptom onset at least
6 months prior to diagnosis