Advances in understanding and treatment of feline inappropriate elimination
TOPICAL REVIEW
Advances in Understanding and Treatment of FelineInappropriate Elimination
Feline inappropriate elimination is the number one behavioral reason for relinquishment of cats to shelters andhas historically been the most commonly reported feline problem addressed by behavior professionals. Veter-inarians are hence challenged to uncover the underlying motivation for this behavior so that an accuratediagnosis can be made and an effective treatment plan implemented. Before a behavioral diagnosis can bemade, underlying medical disease must be addressed, making a comprehensive physical evaluation imperative. After all medical issues have been addressed, a behavior diagnoses list is made based on detailed historicalinformation obtained from the cat owner. A distinction is first established between marking and inappropriatetoileting, according to elimination postures described by the owner and the social relevance of the sites ofinappropriate eliminations. Next, inadequacies of the litter box management are identified and subsequentaversions and preferences, including litter box aversion, substrate aversion, location aversion, substrate pref-erence, and location preference, can be diagnosed. The practitioner should be cognizant of the fact that anxietyfrom the environment and social conflict may play a major role in both marking and inappropriate toiletingbehaviors. Once both the medical and behavioral diagnoses are established, a treatment plan catered to theindividual cat, owner, and household environment can be formulated. This should include acceptable forms ofmarking when indicated, appropriate litter box management and hygiene, reduction of environmental stres-sors, including resolution of social conflict in multicat households, proper treatment and restricted access tosoiled areas, pheromone application, and, when indicated, anxiolytic drug therapy. 2010 Elsevier Inc. All rights reserved. Keywords: cat, feline, elimination, litter box, behavior
Feline inappropriate elimination is defined as urination Making a Diagnosis
and/or defecation outside of an owner-designated elimi-
Before a definitive behavioral etiology for elimination prob-
nation location. Although the cat may not recognize its own
lems can be made, underlying medical disease must be ruled
elimination patterns as problematic, owners of such cats find
out and addressed. Although the medical evaluation should
it quite undesirable, making it the number one behavioral
encompass all physical aspects, special attention should be
reason for relinquishment of cats to and a common
paid to factors causing discomfort to the lower urinary tract
reason for the return of a previously adopted cat to a
(i.e., urinary tract infection, urolithiasis, neoplasia, cystitis)
Furthermore, elimination problems have historically been
or gastrointestinal system (any cause of diarrhea, constipa-
the most commonly reported feline problem addressed by
tion, or pelvic pain), and to organ system or endocrine dis-
ease that might increase elimination volume and, therefore,
that this frequency may be on the This decline in
urgency (i.e., hyperthyroidism, diabetes mellitus, chronic
presentation to behavioral specialists suggests that the gen-
kidney disease). A thorough physical examination and a min-
eral companion animal practitioner is better equipped to di-
imum diagnostic database, including a complete blood
agnose and treat such problems. This article aims to boost
count, serum chemistry profile, total T4, fecal analysis, and
general practitioners’ knowledge regarding the current diag-
urinalysis should rule out most of these factors. Further di-
nosis and treatment strategies available for cats with elimi-
agnostic testing, such as urine culture, abdominal/pelvic ra-
diographs, and abdominal ultrasound, should be performedbased on the results of the minimum database. If a medicaletiology is not determined, then a behavioral diagnosis can be
From the Behavioral Medicine Clinic, The Ohio State University Collegeof Veterinary Medicine, Columbus, OH USA.
pursued. Practitioners should be cognizant that medical and
Address reprint requests to: Meghan E. Herron, DVM, DACVB, The Be-
behavioral pathologies often coexist and both aspects should
havioral Medicine Clinic, The Ohio State University College of Veterinary
be addressed to have a successful treatment outcome. Cats
Medicine, 601 Vernon L. Tharp St, Columbus, OH 43210. E-mail:
suffering from medical disease also benefit from behavioral
2010 Elsevier Inc. All rights reserved. 1527-3369/06/0604-0171\.00/0
The behavioral diagnosis is made based on a complete
behavioral history. Characterization of the elimination hab-
Topics in Companion Animal Medicine
its, such as frequency and duration of the problem, elimina-
tion posture, volume eliminated, location of soiling, and sub-
flowchart for diagnosing feline inappropriate elimination
strates or objects on which the cat eliminates, is pertinent for
a behavioral diagnosis. Information regarding the litter boxcharacteristics and management, as well as litter type, should
also be obtained. Furthermore, environmental and house-hold details, including adults, children, and other animals
When urine marking, the cat assumes a standing posture with
living in or frequenting the home, any recent home renova-
the tail raised and sprays urine back against an object. Often
tions or changes in the daily routine, and presence of outdoor
the tail quivers as a small amount of urine is sprayed and no
cats, is equally important information because it provides a
digging or covering behaviors are Objects
means of identifying underlying stressors that may be con-
marked are typically items of social significance, such as win-
tributing to the elimination behavior. An efficient means of
dows or doors where outdoor cats are detectable, areas of the
collecting elimination, litter box, and environmental infor-
home where interactions of conflict have occurred, or items
mation is having owners complete a behavioral history ques-
containing the scent of a particular person or animal in the
tionnaire, as presented in before the appointment.
Marking from a squatting posture is less com-
Gathering this information allows one to discern the mo-
mon, but should be diagnosed if urine or feces are found
tivation behind the elimination pattern and, therefore assign
deposited primarily in socially relevant locations. Marking
a behavioral diagnosis. Understanding the motivational di-
with feces, middening, is less common and its diagnosis is
agnosis then dictates the path of treatment. The first step in
based on the social importance of the and a lack of
making a behavioral diagnosis is to discriminate between
digging and covering behavior. Urine marking in intact cats is
marking, a form of communication, and inappropriate toi-
a normal signal of reproductive yet 10% of neutered
leting, a means of voiding bladder and/or bowel contents.
males and 5% of spayed females persist in showing urine-
Keep in mind some cats will present with concurrent marking
marking Motivations for neutered cats to urine
Table 1. Feline Behavioral History Questionnaire
1) Does your cat’s urine or stools ever appear abnormal, either inside or outside of the box?2) Does your cat have any history of urinary or gastrointestinal tract problems, including a urinary tract infection or
3) Does your cat urinate outside the box? If so, please list all locations. 4) If your cat urinates outside the box, have you ever witnessed it? If so, please describe your cat’s posture (i.e.,
squatting vs. standing, tail down and to the side vs. erect).
5) Does your cat have bowel movements outside of the litter box? If so, please list all locations. 6) Are there certain objects or materials outside of the box on which your cat will eliminate? If so, what?7) Does your cat cover up his eliminations in the litter box?8) Does your cat ever show scratching or digging behaviors before eliminating outside the box?9) What products do you use to clean areas where your cat has soiled?
1) How many litter boxes do you have?2) Where are the litter boxes located?3) What type of litter do you use? Is this a clumping litter?4) Do some or all of your litter boxes have covers?5) Do some or all of your litter boxes have liners?6) How deep is the litter in the box?7) How often do you scoop the urine or stools from the box?8) How often do you empty the entire contents of the box and clean it?
10) Please list all the people living in your household. 11) Please list all the animals in the household in the order in which they were obtained. 12) If you have a multiple cat household, do you ever notice staring, growling, hissing, chasing, or fighting between
13) How does your pet react to strangers?14) How does your cat react to loud noises?15) Has your household changed since acquiring this pet? If so, when and how?16) Was anything unusual going on in your cat’s environment before the onset of the elimination problem?17) Does your cat have access to the outdoors?18) If you cat is strictly indoors, does he have visual access to outdoor cats? If so, what is his reaction?
Volume 25, Number 4, November 2010 Figure 1. Flowchart for diagnosing feline behavioral inappropriate elimination disorders.
mark include territorial signaling and anxiety associated with
aromatic pine or cedar shavings, or because of an unpleasant
social conflict or environmental Multicat
texture, such as large gravel or A common cause of
households are often the source of anxiety-induced urine
litter box or substrate aversion is the experience of a painful
marking and, in fact, the incidence of marking increases as
bowel movement or urination from medical disease. Once
the number of cats in a home Anxiety as a result
the medical problem has resolved, the cat may still recall the
of household or family changes, poor litter box management,
unpleasant experience and, therefore, avoid the previously
the inability to escape the presence of outdoor cats, or the
used litter box or substrate Signs of “dissatisfaction”
absence of the owner is also a major cause of urine-marking
with the litter box or substrate include a cat that investigates
and then avoids entering a box, avoids digging and circling orcovering waste while in the box, scratches the surrounding
wall or sides of the litter box rather than the litter, andperches on the sides of the Moreover, cats with elim-
Unlike marking, toileting behaviors serve the purpose of
ination problems spend less time in the litter and
voiding bladder and bowel and are associated with a squat-
ting Toileting cats will typically display diggingbehaviors before and covering behaviors after
and will typically deposit a large volume, as would be asso-ciated with a fully voided bladder or bowel, onto a horizontal
A location aversion can develop as the cat has a quarrel with
Toileting behaviors that occur outside of the litter
another household cat, is startled by loud noise or commo-
box are often related to litter box as cats de-
tion, or has difficulty accessing the elimination area. This can
velop aversions to the available litter box options and pref-
be a problem with multiple-cat households where social con-
erences for those outside of the owner-designated elimination
flict may prevent some of the household cats from entering
Determining the specific aversions and preferences
the designated elimination area. Geriatric cats may have dif-
will aid in the diagnosis and treatment of inappropriate toi-
ficulty accessing litter that require the cat’s ascending
or descending a flight of stairs or hurtling gates or otherobstacles that may have been set up to keep other animals or
children from accessing the box. Litter box, substrate, andlocation aversions are not mutually exclusive and often there
Aversion to the litter box can develop as a result of poor
are multiple motivational diagnoses.
cleaning hygiene or from other unpleasant characteristics ofthe box. For example, covered litter boxes may trap odors
and prevent the cat from having a safe vantage point for theapproach of other animals during elimination, causing them
As the various aversions prevent cats from using their desig-
to eliminate in a more open and safe area. Litter boxes that
nated elimination areas, preferences for alternative substrates
are too small, do not contain enough litter, or contain liners
subsequently develop. For example, if the litter box is not
that are potentially aversive for cats with intact can
scooped regularly and the cat chooses to eliminate on another
also create an aversion to the elimination area. Substrate
clean substrate, it may develop a preference for the new, nona-
aversions may develop as a result of scented such as
versive material. Substrate preferences can develop with or
Topics in Companion Animal Medicine
without the presence of an aversion and are most commonly
associated with a preference for soft, absorbable material, such
Cleanliness is crucial in successful litter box management.
as bedding, piles of clothing, and Less common are cats
Proper litter box hygiene can improve both urine marking
that prefer open, hard surfaces, such as wood or linoleum floors.
and inappropriate toileting The box should be
Finally, cats with medical illness that may not have been able to
scooped daily and the contents fully emptied allow-
reach the litter box may develop preferences for substrates on
ing for washing with mild soap and water. Although plastic
liners allow for easy and efficient cleaning, they should beavoided because they are potentially aversive for cats withintact Self-cleaning litter boxes offer increased clean-
liness, but they are avoided by some cats because they are
Location preferences may develop as a result of a cat’s desire
associated with aversive noise and movement. As far as litter
for privacy, preference for a safe, quiet area, or ease of access
type, cats have a natural preference for unscented and finely
to a specific location. Furthermore, cats are attracted to pre-
particulate litter making clumping litter a desir-
viously soiled and may be more likely to eliminate in a
able option. Because strong perfumes and scents can createsubstrate aversions, unscented litter is In fact,
location where other cats have eliminated, or where the cat
one study found that the use of scented litter was associated
eliminated at a time when the litter box was not accessible.
with a higher incidence of elimination A recent
Owners may attempt to relocate the litter box and find the cat
study suggested that the addition of an odor eliminator (Zero
Odor; Zero Odor, LLC, Pound Ridge, New York, USA) tostandard clumping litter increased the attractiveness of thelitter box and decreased the frequency of inappropriate elim-
Each individual cat has a unique threshold for tolerating
Appropriate litter box size, shape, and location may also
poor litter box management. Anxiety-provoking events and
reduce the incidence of inappropriate elimination. Cov-
the presence of underlying stressors can change this threshold
ered litter boxes may trap odors and prevent the cat from
quickly. A cat who previously tolerated a dirty litter box or a
having a safe vantage point for the approach of other
difficult-to-access location may suddenly develop aversions
animals during elimination, making them a less desirable
or preferences with the addition of environmental stressors,
option for most cats. If, however, a covered box is being
such as new pets or people in the home, household renova-
used by at least one cat, the owners should avoid immedi-ately removing the covers from all boxes. Instead, a non-
tions, or agonistic interactions with the owner or other cats.
covered box can be placed next to a frequently used cov-
Furthermore, cats with anxiety about new household mem-
ered box to determine a preference for box type. If the
bers or other household changes may be too nervous to ven-
covered box is then no longer used, it can be removed.
ture to the location of their litter Cats may also toilet
Large, open boxes, such as plastic storage
outside of the litter box as a result of separation
provide room for elimination posturing and pre-elimina-
either during the work day or after an extended absence.
tion/postelimination digging and covering behaviors. This
Although anxiety is more commonly associated with urine
principle of first offering the option of a new box and
marking, it is equally important to recognize when anxiety is
establishing a preference before removing old boxes that
playing a role in inappropriate toileting behaviors and to
are being used by some of the cats in the home applies to all
major litter box conformation changes. In multicat house-holds, the number of litter boxes should equal the numberof cats plus one additional box so that there is always a
box available at any given Each cat should haveaccess to a litter box in a separate, safe, quiet area to
For urine-marking cats, neutering is recommended and
prevent one cat’s blocking another’s access to the litter box
should resolve the problem for 90% of males and 95% of
location. This means owners should offer multiple loca-
For cats that urine mark while standing in the litter
tion options for elimination, including at least one box on
box, the addition of a vertical litter box placed so that the end
each floor of the house. Boxes should be kept at a distance
of the horizontal box fits into it can create an acceptable place
from food and water bowls, as well as loud appliances,
to urine In addition, other forms of marking behav-
such as washer/dryers and furnaces that may have created
ior such as scratch marking should be Sub-
a location aversion. See for details regarding litter
strates such as sisal-covered posts or real bark-covered logs in
frequently visited areas of the home are appealing becausethey allow the cat to hook its claws in the The
remaining basic treatment principles are universal for bothmarking and inappropriate toileting behaviors and can work
Because cats are attracted to previously soiled areas and may
as an adjunct in treating medical elimination problems.
be inclined to overmark or use them for proper
Volume 25, Number 4, November 2010
ate scratching substrates, rotating toy options, and comfort-
Table 2. Basic Recommendations for Litter Box Manage-
also take special care to provide daily social contact with the
cat in this room, such as petting, brushing, or permitting timeto sleep on the owner’s Confinement is also helpful in
establishing substrate and box type preferences in that a
“buffet” of options can be presented in one location. Various
substrates, such as different brands of clay, potting soil, sand,
shredded newspapers, and absorbable pads can be offered in
multiple boxes, as well as varying box For cats
with a preference for hard surfaces, flat pans or trays of
differing material can be offered as When a cat has a
strong aversion to a particular litter box or substrate based
on a frightening or painful experience, the “buffet” of box
options offered may need to be substantially different than
the original box. Once a substrate and box preference has
been established and the cat is eliminating appropriately, the
preferred box/litter type can be used through the home and
the cat’s access to the home can be slowly
clean with soap and waterAutomatic/self-cleaning
Because social distress and anxiety are common underlying
components in urine marking for neutered cats, reducingstress and intercat conflict is key. A starting point for reduc-
*Some cats prefer covers. Offer an uncovered box next to a covered box to determine preference.
ing stressors is providing 1) a living space that keeps the catfree from fear and distress and 2) a predictable daily routine
†Fastidious daily scooping may allow for longer time between cleaning.
and owner interactions over which the cat perceives it hassome Cats should have full access to areas ofthe house where stressors, such as loud noises, dogs, other
cleaning is necessary. Although a variety of pet waste clean-
cats in the household, outdoor cats approaching the windows,
ing products exist, studies have shown that enzymatic clean-
and pursuit by small children, are minimized. Throughout
ers are the most effective at reducing and preventing the
the household, cats need perching options that offer safety
return of urine If the problem is chronic, the un-
and a decent vantage point above people and other animals.
derlying carpet pads and baseboards may need to be replaced
If the cat is agitated by cats outside the home, windows out
to completely eliminate excrement Once the areas
which the cat has visual access should be In mul-
have been treated, the cat’s ability to resoil them should be
ticat households there should be enough space for each cat to
managed. This can be accomplished by placing plastic or foil
keep a social distance of at least 1 to 3 when they are in
coverings on top of them to create an unappealing tactile
a room together. Some cats will rest together and groom/rub
sensation when the cat walks in that area and to preventresoaking of the carpet, should another elimination incidentBlocking access to bedding and picking upthrow rugs and laundry are also important for cats with soft
Table 3. Checklist for Creating a Cat “Safe Haven.” The
substrate preferences. Should the cat repeatedly soil a partic-
Following Table Lists Recommendations for Creating a
ular area despite these changes, it may be an indication of a
Safe Refuge for a Cat Inside the Home.
location preference and a litter box should be placed directly
Scratching optionsHiding placesHigh resting areas/perches
In some cases the cat’s access to previously soiled areas must
completely restricted. If the soiling is limited to one room in
the home, that room can be closed off from access. If there are
Other pets in the home causing social conflict are denied
multiple areas or if the main area cannot be blocked off, then
accessVisual access to outdoor cats blocked
the cat should be confined to a room or “safe haven” when
Soft music to muffle sounds outside of area
not directly supervised. Within this “safe haven” there
should be fresh food and water, clean litter boxes, appropri-
Topics in Companion Animal Medicine
each other in an affiliative manner, while most cats use the
same resting/perching sites at different times per
Early studies indicated moderate efficacy with the use of pro-
Hence, it is important to offer multiple safe and comfortable
gestins for urine marking in Because of the high
potential for adverse effects, such as diabetes mellitus and
One means of providing the individual cat with a low-
bone marrow and the development of safer,
stress environment is to set up a refuge from household stres-
more effective drugs, progestin treatment has fallen out of
sors. Each cat should have access to its own quiet area of the
favor. The benzodiazepine, diazepam, was found to reduce
home or “safe haven” Electronic cat doors can be
urine marking in 55% of treated however, accounts of
installed to allow access only to the individual cat wearing
acute fulminant hepatic failure after oral administration have
the door-activating In single-cat households, a baby
been making its use potentially hazardous.
gate raised several inches in the door jamb will permit the cat
Later, treatment with the azapirone, buspirone (0.5-1 mg/kg
to enter the room, keeping out dogs and small children.
every 12 showed some promise in controlling urinemarking in multiple-cat but reports of in-
creased intercat aggression problems have been More recently, several studies have demonstrated efficacy of
Punishment should be avoided in both marking and toileting
clomipramine (0.25-1.3 mg/kg every 24 in treating
problems. Because many elimination problems are based in
urine marking in Clomipramine is a tricyclic antide-
anxiety or social conflict, punishment is likely to exacerbate
pressant whose serotonin-enhancing properties are effective
the problem. Should an owner catch a cat in the act of elim-
at reducing Side effects may include sedation, con-
inating outside of the box, the behavior can be calmly inter-
stipation, urine retention, pupil dilation, and appetite
rupted with as little movement as possible on the owner’s
changes. Daily doses less than 0.5 mg/kg are associated with
In the author’s experience, teaching the cat an “inter-
fewer side Even greater efficacy for the treatment of
ruptor” cue and then redirecting the cat to an appropriate
urine marking can be gained with the use of the selective
elimination site can be beneficial. The interruptor cue is
serotonin reuptake inhibitor fluoxetine (0.5-1.5 mg/kg every
taught pairing a sound (nonstartling), such as the shaking or
24 In fact, one study found that 100% of cats
crinkling of a treat pouch or the jingling of a bell, with the
treated with 1 mg/kg of oral fluoxetine once daily had a 90%
cat’s favorite food treat, a process known as classical condi-
or greater reduction in marking Because the se-
Once conditioned, the owner can use this cue to
lective serotonin reuptake inhibitors as a class are more se-
interrupt early elimination postures, call the cat away from
lective for serotonin enhancement and do not have major
its intended elimination area, and then give the food reward
anticholinergic/anti-adrenergic properties, fluoxetine is asso-
for compliance. For cats with inappropriate toileting prob-
ciated with fewer side effects than the tricyclic antidepres-
lems, they can then be calmly taken to the litter box and
sants, with decreased appetite and lethargy being the most
praised and given another food treat for appropriate elimi-
common. Suppression of appetite is of concern, especially
This method gives the owner a means of stopping
with finicky eaters or obese cats; therefore, caution should be
undesirable elimination without causing fear or anxiety,
exercised with fluoxetine use in such cases. Finally, a pilot
study using the dietary supplement (Anxitane; Virbac AnimalHealth, Fort Worth, Texas, USA) containing L-theanine hasshown promise in treating anxiety problems in cats, includ-
ing inappropriate L-theanine is an amino acidfound in green tea and has been shown to promote mental
The pheromone product Feliway (Ceva Animal Health, Inc.,
and physical relaxation in Further studies are
St. Louis, Missouri, USA) has been shown to reduce the oc-
needed to determine its safety and efficacy in feline elimina-
currence of urine marking as well as to increase relaxed be-
havior in stressful Hence, its use may be
Regardless of drug class, efficacy, or side effects, it is im-
beneficial in cases in which stress or anxiety is an underlying
portant to recognize that no psychotropic drugs are labeled
factor in the elimination problem. Feliway is an analog of the
for use in cats. Cat owners should be made aware of the
facial pheromone deposited when cats facially rub or bunt on
off-label use and cautioned regarding potential side effects
objects—a behavior performed when cats feel comfortable
and toxicities. In addition, the use of psychotropic drugs
with their Because cats do not typically urine
should be an adjunct to environmental changes and proper
mark in locations where they have deposited facial phero-
litter box management. The precise starting dose and dura-
mones, it serves as an antagonist of urine marking. For cases
tion of drug therapy vary with each cat. Starting at or below
of urine marking, Feliway can be sprayed directly to marked
the published dose range and titrating up to effect over sev-
areas 1 to 3 times Alternatively, a plug-in diffuser can
eral weeks is recommended. Typically, several months at the
be used to obtain a broader and more consistent distribution
maintenance dose are necessary to obtain acceptable resolu-
of the pheromone product in a particular room of the
tion. Once the new elimination habits have developed and
been maintained for 2 to 3 months, the medication can be
Volume 25, Number 4, November 2010
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UNITED STATES DISTRICT COURT WESTERN DISTRICT OF NEW YORK ABBOTT LABORATORIES and LABORATOIRES FOURNIER S.A., Plaintiffs, ________ BIOVAIL LABORATORIES INTERNATIONAL SRL and BIOVAIL CORPORATION, COMPLAINT FOR PATENT INFRINGEMENT Defendants. Abbott Laboratories ("Abbott") and Laboratoires Fournier S.A. ("Fournier") for their Complaint
Cyclosporine Concentration Prediction usingG. Camps-Valls∗, E. Soria-Olivas∗, J. J. P´erez-Cruz‡, A. R. Figueiras-Vidal‡, A. Art´∗ Dept. Enginyeria Electr`onica. Universitat de Val`encia, Spain. C/ Dr. Moliner, 50, 46100 - Burjassot (Val`† Pharmacy Service. Dr. Peset University Hospital. Val`encia, Spain∗. ‡ Dpto. Teor´ıa de la Se˜nal y las Comunicaciones. Universidad Ca