The toolbox beginning on the next page was compiled to provide several documents that will assist you with treating your clozapine patients. It includes a suggested protocol for initiating someone on clozapine (see Figure 1). We have also included guidelines for CBC monitoring (see Table 1), at initiation and beyond, as well as monitoring recommendations for when an interruption in treatment occurs (see Figure 2). Since constipation is a major adverse event associated with the use of clozapine, attached you will find an overview of both prevention and treatment of constipation compiled by Beth Hall at Fulton State Hospital in Missouri (see Figure 3). Another side effect that often afflicts a person taking clozapine is hypersalivation. Here, we have a table which outlines options to minimize one's sialorrhea (see Table 2). Or read this Current Psychiatry clinical pearl which discusses pharmacologic treatments for hypersalivation. We hope that these documents are helpful with regard to a patient's clozapine treatment.

Figure 1.

PHYSICIAN'S ORDERS FOR CLOZAPINE INITIAL TITRATION PROTOCOL

Figure 1.

PHYSICIAN'S ORDERS FOR CLOZAPINE INITIAL TITRATION PROTOCOL

Figure 2.

TRACKING PATIENTS: RESUMING MONITORING FREQUENCY AFTER INTERRUPTION IN THERAPY

Figure 2.

TRACKING PATIENTS: RESUMING MONITORING FREQUENCY AFTER INTERRUPTION IN THERAPY

Figure 3.

PHARMACY CONSTIPATION PROTOCOL, MAR 2011

Figure 3.

PHARMACY CONSTIPATION PROTOCOL, MAR 2011

Table 1.

Frequency of monitoring based on stage of therapy or results from WBC count and ANC monitoring tests

Frequency of monitoring based on stage of therapy or results from WBC count and ANC monitoring tests
Frequency of monitoring based on stage of therapy or results from WBC count and ANC monitoring tests
Table 2.

MHC's Strategies to Treat Clozapine Hypersalivation

MHC's Strategies to Treat Clozapine Hypersalivation
MHC's Strategies to Treat Clozapine Hypersalivation

Constipation

Constipation is an often misunderstood, poorly defined side effect of many medications. Due to the prevalence of occurrence with opiates, the link between, and treatment of constipation induced by opiates is relatively well understood. The constipation induced by psychotropic medications is however, far less understood.

Constipation is many different things to many different people. However, Rome-III criteria gives the following definition:

“To have the diagnosis of functional constipation, the patient must satisfy two or more of the following diagnostic criteria:

  • Straining during at least 25% of defecations

  • Lumpy or hard stools in at least 25% of defecations

  • Sensation of incomplete evacuation in at least 25% of defecations

  • Sensation of anorectal obstruction / blockage for at least 25% of defecations

  • Manual maneuvers to facilitate at least 25% of defecations

  • Fewer than three defecations per week”

In a population of known poor informants, it is often difficult to determine the symptoms and complaints regarding constipation. However, it is important to be vigilant in looking for them, as many of the medications used to treat psychosis and their side effects are known to induce constipation. A list of prominent constipating medications is listed later.

Constipation is commonly associated with impaired quality of life, but can have potentially fatal consequences. In a literature review of second generation antipsychotics and constipation, there was a significant amount of data to indicate potentially toxic complications of these medications. These ranged from high rates of untreated constipation to paralytic ileus. Some also reported bowel perforation due to clozapine, gangrenous bowel, fecal impaction, megacolon, and aspiration of feculent vomitus.

Lifestyle Modifications

No matter what the cause of constipation, various measures have been shown to reduce, and possibly even eliminate this problem. First and foremost, increase the hydration status of the individual. While typically unnecessary, individuals who are dehydrated suffer from constipation as a result of their body trying to retain as much water as it can. Restoration of hydration typically cures the incident of constipation, and ensuring they maintain hydration prevents any further bouts. Secondly, most professionals recommend an increase in dietary fiber. Due to the processed nature of most of our foods, our typical fiber intake is far less than the recommended 25g daily intake. Most fiber should come in the form of food; however fiber supplementation can provide benefit to those who cannot achieve this. Lastly, and most importantly, increased exercise has been show to support many aspects of health. Exercise promotes well-being, decreases stress, and promotes colonic movement. By increasing exercise, you promote overall health, as well as symptom relief and prevention of constipation. These three aspects, and in particular exercise, should form the backbone of any treatment of constipation – be it acute, occasional, or chronic.

Description of All Available Agents:

  • Benefiber

    • Also known as Partially Hydrolyzed Guar Gum (PHGG), Resource Benefiber is a soluble, non-viscous fiber supplement that has been proven effective in the treatment of acute and chronic constipation. It is inexpensive, effective, and our fiber of choice.

  • Bisacodyl (Dulcolax)

    • Described as a stimulant laxative, it functions by directly inducing colonic peristalsis. It is metabolized by brush border enzymes, with the active metabolite acting on the mucosa of the intestine. Highly effective at inducing bowel movements, it also slightly softens them by peristalsis. However, it is commonly given in conjunction with a stool softener.

  • Docusate (Colace)

    • A common stool softener, it functions as a surfactant, facilitating the mixture of fat and water. By assisting in combining water and stool fat, it ‘softens’ the stool. This provides a literally ‘softer’ stool, decreasing straining and discomfort associated with hard stool.

  • Lactulose

    • A sugar that is poorly absorbed by the intestine, and has no enzyme capable of breaking it down in the intestine. It thus reaches the colon relatively unchanged, where flora then break it down into lactic acid. This causes an increase in osmotic pressure, increasing stool water content, softening it. It also increases the frequency of bowel movements.

  • Metamucil

    • A brand name form of psyllium, a husk of the seed plantago ovata. Functioning as a bulk laxative, studies have indicated that it increases stool frequency, consistency, and ease of evacuation.

  • Mineral Oil

    • A heavy oil. When drank in sufficient quantities, it coats the bowel (and stool) with a hydrophobic film. This helps retain moisture in the lumen as well as the stool. This stimulates a bowel movement as well as easing evacuation. Contraindicated for long- term use due to toxic build up, and inhibition of absorption of several nutrients.

  • Magnesium Citrate

    • An osmotic laxative, it works by generating an osmotic gradient to pull water from surrounding tissues. The increased retention distends the colon, causing increased peristaltic activity. It should not be given to individuals with renal impairment due to potentially toxic magnesium accumulation.

  • Magnesium Hydroxide (Milk of Mag)

    • A hyperosmotic laxative, it works by generating an osmotic gradient to pull water from surrounding tissues. By indiscriminately pulling water from surrounding tissues, it is effective in rapidly emptying the lower intestine and bowel. It however also increases the risk of dehydration and electrolyte abnormalities. It should not be given to individuals with renal impairment due to potentially toxic magnesium accumulation.

  • Polyethylene Glycol 3350 (Miralax)

    • A widely studied polyether compound, it functions as an osmotic laxative. By increasing the osmotic gradient, it stimulates the movement of water into the lumen of the intestine. Doing such encourages more water to remain in the intestine, forming a softer, easier to pass stool, while prompting a bowel movement.

  • Sennosides (Senokot)

    • Plant compounds found in the Senna family. They are anthraquinone derivatives, and work by stimulating the nerve endings in the colon. In doing such, they force the muscles to contract more often and with more force (increase peristalsis), prompting a bowel movement. Found to be particularly effective in the treatment of opiate-induced constipation.

PROMINENT CONSTIPATING MEDICATIONS

  • Aripiprazole (13%)

  • Baclofen

  • Benztropine

  • Bromocriptine

  • Celecoxib

  • Chlorpromazine

  • Clozapine (14%)

  • Codeine

  • Diphenhydramine

  • Divalproex (4%)

  • Escitalopram

  • Ferrous Sulfate

  • Fluoxetine

  • Fluphenazine

  • Fluvoxamine

  • Gabapentin

  • Haloperidol

  • Hydrocodone

  • Lamotrigine

  • Levetiracetam

  • Loxapine

  • Memantine (5%)

  • Meperidine

  • Morphine Sulfate

  • Naproxen

  • Olanzapine (9–11%)

  • Oxycodone

  • Paroxetine

  • Perphenazine

  • Phenytoin

  • Piroxicam

  • Pregablin

  • Prochlorperazine

  • Quetiapine (9%)

  • Risperidone (7–13%)

  • Sertraline

  • Thioridazine

  • Tizanidine

  • Topiramate

  • Trifuloperazine

Constipation Protocol: Works Cited

Constipation Protocol: Works Cited
1.
Chatoor
,
D.
,
Emmanuel
,
A.
Constipation and Evacuation Disorders
.
Best Practice & Research Clinical Gastroenterology
.
23
(
2009
)
517
30
2.
Emmanuel
,
A.
,
Tack
,
J.
Quigley
,
E.
,
Talley
,
N.
Pharmacological Management of Constipation
.
Neurogastroenterol Motil
(
2009
)
21
(
suppl. 2
),
41
54
3.
De Hert
,
M.
,
et al
.
Second-Generation Antipsychotics and Constipation: A Review of the Literature
.
European Psychiatry
(
2010
).
4.
Giannini
,
E.
,
Mansi
,
C.
,
Dulbecco
,
P.
,
Savarino
,
V.
Role of Partially Hydrolyzed Guar Gum in the Treatment of irritable Bowel Syndrome
.
Nutrition
22
(
2006
)
334
342
.
5.
Longstreth
,
G.
,
et. al
.
Rome 3: Functional Bowel Disorders
.
Gastroenterology
2006
;
130
:
1480
1491
.
6.
McCallum
,
I.
,
Ong
,
S.
,
Mercer-Jones
,
M.
Chronic Constipation in Adults
.
BMJ
,
28 Mar 2009
.
338
(
763–6
).
7.
Mihaylov
,
S.
,
et. al
.
Stepped Treatment of Older Adults on Laxatives. The STOOL Trial
.
Health Technology Assessment
2008
;
12
(
13
).
8.
Mueller-Lissner
,
S.
The Pathophysiology, Diagnosis, and Treatment of Constipation
.
Dtsch Arztebl Int
2009
;
106
(
25
):
424
32
9.
National Institute of Diabetes and Digestive and Kidney Diseases
. (
2007
).
Constipation. (NIH Publication No. 07-2754)
.
10.
Ternent
,
C.
,
et. al
.
Practice Parameters for the Evaluation and Management of Constipation
.
Dis Colon Rectum
2007
;
50
:
2013
2022
.

REFERENCES

REFERENCES
1.
Clozapine Initial Titration Protocol” adapted from the Center for Behavioral Medicine's form
.
2.
CBC monitoring from Clozaril Package insert, Novartis. Last revised, December 2010
.
3.
Sockalingam
S
,
Shammi
C
,
Remington
G
.
Clozapine-induced hypersalivation: a review of treatment strategies
.
Can J Psychiatry
.
2007
;
52
(
6
):
377
84
.
PubMed PMID: 17696024
.
4.
Liang
CS
,
Ho
PS
,
Shen
LJ
,
Lee
WK
,
Yang
FW
,
Chiang
KT
.
Comparison of the efficacy and impact on cognition of glycopyrrolate and biperiden for clozapine-induced sialorrhea in schizophrenic patients: a randomized, double-blind, crossover study
.
Schizophr Res
.
2010
;
119
(
1–3
):
138
44
. .
5.
Sharma
A
,
Ramaswamy
S
,
Dahl
E
,
Dewan
V
.
Intraoral application of atropine sulfate ophthalmic solution for clozapine-induced sialorrhea
.
Ann Pharmacother
.
2004
;
38
(
9
):
1538
.
DOI: 10.1345/aph.1E077. PubMed PMID: 15252196
.
6.
Lamba
G
,
Ellison
JM
.
Reducing clozapine-induced hypersalivation
.
Current Psychiatry
.
2011
;
10
(
10
);
77
8
.