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Clinical features and outcome in dogs and cats with obsessive-compulsive disorder: 126 Cases (1989-2000)


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To determine clinical features and outcome in dogs and cats with obsessive-compulsive disorder (OCD). Retrospective study. 103 dogs and 23 cats. Records of patients with OCD were analyzed for clinical features, medication used, extent of behavior modification, and outcome. Most dogs affected with OCD had been obtained from breeders. Male dogs significantly outnumbered females (2:1). Female cats outnumbered male cats by 2:1 in a small sample. Most affected dogs lived in households with 2 or more humans and other dogs or cats, and had some formal training. Client compliance with behavior modification was high. A combination of behavior modification and medication resulted in a large decrease in intensity and frequency of OCD in most animals. Clomipramine was significantly more efficacious for treatment in dogs than was amitriptyline. Only 1 dog and 1 cat were euthanatized because of OCD during the study. OCD in dogs does not appear to be associated with lack of training, lack of household stimulation, or social confinement. In cats, OCD may be associated with environmental and social stress. Obsessive-compulsive disorder appears at the time of social maturity and may have sporadic and heritable forms. With appropriate treatment (consistent behavior modification and treatment with clomipramine), frequency and intensity of clinical signs in most dogs and cats may decrease by > 50%. Success appears to depend on client understanding and compliance and the reasonable expectation that OCD cannot be cured, but can be well controlled.
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bsessive-compulsive disorder (OCD) in pet dogs
and cats is usually recognized because of a com-
pulsive component (ritualistic, stereotypic behaviors).
Obsessive-compulsive behaviors in dogs can include
those characterized by circling, tail chasing, flank suck-
ing (particularly in Doberman Pinschers), fence run-
ning, fly biting, self mutilation, hair or air biting, pica,
pacing or spinning, staring and vocalizing, some aggres-
sions, self-directed vocalizing, and fabric sucking or
chewing. In cats, self-mutilation, excessive grooming,
tail chasing, and wool or fabric sucking or chewing are
also signs of OCD.
Because behaviors seen in OCD are
often normal behaviors performed in an inappropriate,
excessive, or out-of-context manner,
history becomes
particularly important in elucidating whether the
patient truly has OCD. The purpose of this retrospec-
tive study was to determine clinical features, response
to treatment, and outcome in dogs and cats with OCD.
Criteria for Selection of Cases
All dogs and cats seen at the Behavior Clinic of the
University of Pennsylvania from January 1989 through
December 2000 were assessed for OCD as part of a
thorough history and by use of a standardized ques-
Inclusion criterion was a diagnosis of OCD
made on the basis of finding repetitive, stereotypic
motor, locomotory, grooming, ingestive, or hallucino-
genic behaviors that occurred out of context or in fre-
quency or duration in excess of that required to accom-
plish the ostensible goal or in a manner that interfered
with the animal’s ability to function in its social envi-
As a result of the standardized screening
of all patients, the diagnosis of OCD was made for
some patients for whom the affiliated behaviors were
not the clients’ primary complaint, and in a few ani-
mals the diagnosis of OCD was secondary to another
primary condition (eg, obsessive-compulsive spinning
and barking that is particularly performed during
bouts of separation anxiety).
From the medical records, patients were classified
by breed; weight; sex and neuter status; age at neuter-
ing; age at onset of OCD; source; number of humans,
cats, and dogs in the household; training or schooling;
duration of treatment; class of OCD (hallucinatory,
vocalization, locomotory, grooming or self-mutilation,
ingestion [pica or coprophagy])
; whether other
dogs or cats in the household had the same or similar
behavior and if so, which animals; concurrent behav-
ioral diagnoses; medication used and duration; extent
of behavior modification; and outcome.
For assessment of animal age and duration of
OCD, actual birth dates were used when known. If the
day was unknown but the month of birth was known,
the patient was assigned a birth day of 15. If both
month and day were unknown, the patient was
assigned a birth date of June 30 of the year suspected
to be the birth year.
JAVMA, Vol 221, No. 10, November 15, 2002 Scientific Reports: Retrospective Study 1445
Clinical features and outcome in dogs and cats
with obsessive-compulsive disorder:
126 cases (1989–2000)
Karen L. Overall, VMD, PhD, DACVB, and Arthur E. Dunham, PhD
Objective—To determine clinical features and out-
come in dogs and cats with obsessive-compulsive
disorder (OCD).
Design—Retrospective study.
Animals—103 dogs and 23 cats.
Procedures—Records of patients with OCD were
analyzed for clinical features, medication used, extent
of behavior modification, and outcome.
Results—Most dogs affected with OCD had been
obtained from breeders. Male dogs significantly out-
numbered females (2:1). Female cats outnumbered
male cats by 2:1 in a small sample. Most affected
dogs lived in households with 2 or more humans
and other dogs or cats, and had some formal train-
ing. Client compliance with behavior modification
was high. A combination of behavior modification
and medication resulted in a large decrease in inten-
sity and frequency of OCD in most animals.
Clomipramine was significantly more efficacious for
treatment in dogs than was amitriptyline. Only 1 dog
and 1 cat were euthanatized because of OCD during
the study.
Conclusions and Clinical Relevance—OCD in dogs
does not appear to be associated with lack of training,
lack of household stimulation, or social confinement.
In cats, OCD may be associated with environmental
and social stress. Obsessive-compulsive disorder
appears at the time of social maturity and may have
sporadic and heritable forms. With appropriate treat-
ment (consistent behavior modification and treatment
with clomipramine), frequency and intensity of clinical
signs in most dogs and cats may decrease by > 50%.
Success appears to depend on client understanding
and compliance and the reasonable expectation that
OCD cannot be cured, but can be well controlled.
J Am Vet Med Assoc
From the Biology Department (Dunham) and the Center for
Neurobiology and Genetics-Psychiatry Department, School of
Medicine (Overall), University of Pennsylvania, Philadelphia,
PA 19104.
Data entry was supported by Novartis Animal Health, Greensboro,
NC; medication for some patients was provided by CIBA, Summit,
NJ, and Novartis Animal Health, Greensboro, NC.
The authors thank Len Rhone and Ken Mullin for technical assis-
Address correspondence to Dr. Overall.
Sources of animals included stray or found, breed-
er (serious or show), breeder (backyard), Society for
the Prevention of Cruelty to Animals or humane shel-
ter, breed rescue service, newspaper adoption adver-
tisement (not breeder), pet store, friend, and other.
Training or schooling categories included no school,
trained by client, puppy kindergarten, group lessons
(basic), group lessons (advanced), private trainer at
house, and private trainer (sent to trainer).
The general behavior modification scheme for dogs
consisted of 3 basic steps designed to stop unwanted
behaviors and reward preferable behaviors that were
directly competitive with the undesirable behaviors. In
step 1, clients were to cease even unintentional reward
for the undesirable behavior. In step 2, clients were
asked to follow a passive behavior modification pro-
gram designed to teach dogs to sit quietly, look at the
person from whom they were seeking attention or with
whom the interaction was occurring, and wait to take
the cues about the appropriateness of their behavior
from those people (ie, Protocol for Deference
). In step
3, clients were requested to begin active behavior mod-
ification designed to teach the dogs to relax when they
would otherwise be engaged in the behavior, in
exchange for which the dog was given a food or play
reward (ie, Protocol for Relaxation: Tier 1
For clients with feline patients, steps 1 and 3 were
recommended; step 2 was modified to recommend that
the client only interact with the cat when the cat was
calm. Cats were not required to sit in step 3, although
this was encouraged, but the clients were advised to
engage the cat in an enjoyable behavior that was direct-
ly competitive with the undesirable behavior.
Behavior modification was assessed on the basis of
client responses and clinician opinion.
For some of the patients, medication had been pre-
scribed by the referring veterinarian. When the first
patient in this study was treated, treatment with tricyclic
antidepressants (TCAs; eg, clomipramine and specific
serotonin reuptake inhibitors [SSRIs]) was cost pro-
hibitive (> $10/d). Clomipramine is now affordable and
available in a canine formulation.
Accordingly, the TCA
(amitriptyline) was the first drug of choice for all
patients with conditions that primarily involved anxiety
and were enrolled in the early portion of the study.
Clomipramine was only used instead of amitriptyline if
amitriptyline was not efficacious or caused gastrointesti-
nal disorders. Because of its histamine-1 receptor antag-
onist properties, the TCA doxepin was the first drug of
choice for conditions that primarily involved pruritus,
followed by amitriptyline.
Other medications were
occasionally prescribed as dictated by alterations in the
patients’ behaviors, and for some animals, combinations
of medications were both more efficacious and more
cost-effective for clients, as described elsewhere.
When the senior author was awarded a grant pro-
viding clomipramine at no cost, clomipramine was used
as the first drug of choice for treating OCD, as it has
been in humans. This circumstance allowed us to retro-
spectively compare the relative effects of amitriptyline
and clomipramine for patients that met the criteria for
OCD. If a patient was administered amitriptyline and
acceptable results were obtained (marked decrease in
intensity and frequency of OCD behaviors), administra-
tion of the drug was maintained and treatment was con-
sidered successful. If a patient was treated initially with
amitriptyline and acceptable results were not obtained,
clomipramine was administered instead; if acceptable
results were obtained with clomipramine, treatment
with amitriptyline was considered a failure and treat-
ment with clomipramine was considered a success.
Patients for whom treatment with clomipramine failed
were likewise treated with another medication.
Dosage protocols
were used consistently and
included amitriptyline (1 mg/kg [0.45 mg/lb], PO, q 12
h for 10 days; if no change in behavior was detected,
the dosage was increased to 2 mg/kg [0.91 mg/lb] for
10 days; if still no change was detected, the medication
was changed [if treatment was efficacious it was con-
tinued for a minimum of 1 month]); doxepin (3 to 5
mg/kg [1.4 to 2.3 mg/lb], PO, q 8 h to q 12 h for a min-
imum of 1 month); clomipramine (1 mg/kg, PO, q 12
h for 14 days, then 2 mg/kg, PO, q 12 h for 14 days,
then 3 mg/kg, PO, q 12 h for 1 month, for a minimum
of 2 months of treatment [the gradual increase in
dosage was intended to minimize gastrointestinal dis-
orders]); and the SSRIs, sertraline and fluoxetine (1
mg/kg, PO, q 24 h for 2 months initially). Treatment
was then continued at the minimum effective dose nec-
essary to control the behavior.
All patients received full physical and laboratory
evaluation prior to treatment. Any nonspecific derma-
tologic, medical, or neurologic signs potentially associ-
ated with OCD were evaluated by the veterinarians
trained in the respective specialty prior to behavioral
treatment. When warranted, patients also received var-
ious nonroutine diagnostic procedures (eg, assessment
of thyroid function and magnetic resonance spec-
troscopy of the brain).
Eight clinicians were involved in evaluation of the
dogs reported here. All clinicians adhered to the same
diagnostic criteria, and at least 2 clinicians reviewed each
diagnosis. Although many records contained detailed out-
come data, quality of the description of the behaviors
depended on clinician expertise versus resident expertise,
whether the behaviors were videotaped, client capability
and motivation in keeping data logs, and knowledge
accrued by managing increasing numbers of these dogs.
Accordingly, outcomes were broadly grouped and statisti-
cally treated as class variables to evaluate older and newer
cases equivalently. Response variables for outcome were
small decrease in intensity ( 50%), large decrease in
intensity (> 50%), small decrease in frequency ( 50%),
large decrease in frequency (> 50%), the behavior stopped
totally, no change, small increase in intensity (< 50%),
large increase in intensity (> 50%), small increase in fre-
quency (< 50%), large increase in frequency (> 50%),
died, euthanatized because of OCD, euthanatized for
other reasons, placed, other, and unknown. Patients clas-
sified with unknown outcomes were those lost to follow-
up. For patients with concurrent behavioral diagnoses,
alterations in intensity and severity reported here pertain
only to OCD.
Data were analyzed by use of the log-likelihood
ratio test, and relevant nonparametric tests as indicat-
ed for categoric data.
1446 Scientific Reports: Retrospective Study JAVMA, Vol 221, No. 10, November 15, 2002
One hundred three dogs met inclusion criteria,
including 5 sexually intact females, 26 spayed females,
20 sexually intact males, and 52 neutered males.
Twenty-three cats (1 sexually intact female, 14 spayed
females, 1 sexually intact male, and 7 neutered males)
that met the diagnostic criteria had sufficiently com-
plete records to be included in the study.
Category of OCD—The most common category of
OCD in dogs was that associated with grooming or
self-mutilation, followed by OCD involving locomo-
tion and OCD involving signs of hallucinations (Fig 1).
For cats, the most common category of OCD involved
grooming or self-mutilation (Fig 2).
There was no significant association (log likeli-
hood ratio test) between sex and neuter status catego-
ry of affected dogs and the category of OCD they had.
However, compared with the sex and neuter data for
the entire veterinary teaching hospital canine popula-
tion during the study period (n = 47,473), male dogs
were significantly over-represented in the OCD popu-
lation (log likelihood ratio test statistic, G
adjusted (adj)
13.256 [P < 0.05]). In addition, neutered males were
over-represented in the OCD population, compared
with non-neutered males (log likelihood ratio test sta-
tistic, G
= 36.641 [P 0.001]).
Breed—The population of dogs with OCD com-
prised 18 mixed-breed dogs; 12 German Shepherd
Dogs; 7 Rottweilers; 6 Golden Retrievers; 5 each of
Dalmatians, Labrador Retrievers, and Lhasa Apsos; 3
each of Doberman Pinschers, Poodles, Soft-Coated
Wheaten Terriers, and English Springer Spaniels; 2
each of American Pit Bull Terriers, Bulldogs, Great
Danes, Miniature Schnauzers, and Cocker Spaniels;
and 1 dog each of 22 other breeds. This distribution
did not differ significantly from that in the overall
canine population of the Behavior Clinic or of the vet-
erinary teaching hospital. Further examination of the
most common breeds of dogs (mixed breeds, German
Shepherd Dogs, Rottweilers, Dalmations, and
Bulldogs) revealed interesting patterns among the
breeds. The specific manifestations of the OCD
appeared to be associated with the tasks for which the
dogs were developed. Dogs of herding breeds often had
excessive tail chasing. Dogs of guarding breeds and
those selected for intense focus and tenacity (eg,
Dalmatians, Rottweilers, and German Shepherd Dogs)
often had signs of hallucinations. All Rottweilers and
all but 1 Dalmatian had signs of hallucinations. Nine of
12 German Shepherd Dogs chased their tails.
The cat population consisted of 14 Domestic
Shorthairs, 6 Siamese, 1 Devon Rex, 1 Russian Blue,
and 1 Bengal. Siamese cats commonly had pica involv-
ing sucking, chewing, or ingestion of fabrics; 2 of the 6
Siamese cats in the study chewed, sucked, or ingested
fabric; and 1 ingested electric cords. All cats that
ingested fabric were Siamese, but neither cats that
licked plastic substrate or had sucking behavior cate-
gory were. The Bengal cat had over-grooming and
urine marking, both anxiety-related conditions. The
small number of cats we evaluated precluded statistical
comparisons among breeds. The behaviors associated
with OCD appeared after trauma in 3 cats and after
changes in feline or human social circumstances or
relationships in 7 cats. The changes in the feline or
human relationships were also often associated with
intercat aggression or elimination abnormalities (9
cats). Grooming or self-mutilation involved 16 of the
cats, 3 of which had a previous diagnosis of hyperes-
thenia and 3 of which had a diagnosis of atopy.
Age of onset—Age of onset was known or confi-
dently estimated for 95 of the 103 dogs. Mean ± SD age
at onset was 20.3 ± 23.7 months; however, the fre-
quency distribution of age at onset was highly skewed
(skewness, 3.214). Age of onset for cats was 28.2 ±
30.1 months (n = 21), and the frequency distribution
JAVMA, Vol 221, No. 10, November 15, 2002 Scientific Reports: Retrospective Study 1447
Figure 2—Frequency (%) distribution of categories of OCD in 23
Figure 1 for key.
Figure 1—Frequency (%) distribution of categories of obsessive-
compulsive disorder (OCD) in 103 dogs. M = Self-mutilation
(grooming). L = Locomotor (spinning, chasing). H = Hallucinatory.
P = Pica. V = Vocalization. K = Licking. C = Coprophagy. S =
Sucking. D = Digging. O = Other.
was less skewed (skewness, 1.14) than that of the dog
population. Median age of onset for cats and dogs was
12 months, indicating that half of the patients devel-
oped signs of OCD by the age of 1 year.
Source—Almost 60% of the dogs in this study
originated from either serious show breeders (54.4%)
or backyard breeders (4.9%). These categories were
self-assigned by the dog owners, so the low percentage
of backyard breeders may have been an underestimate.
Only 9% of dogs came from pet stores, whereas 11%
came from humane shelters.
Six of the cats came from friends, 5 came from
either serious show breeders or backyard breeders, 5
were found or were stray, 3 came from humane shel-
ters, and 4 came from miscellaneous sources.
Size of human and pet households—Only 18
(17.5%) of the dogs in this study lived in single-human
households; 46 (44.7%) lived in households with 2
humans, and 39 (37.7%) lived in households with 3 or
more humans. More than half of the dogs in this study
had other dogs in the household, and almost 30% had
cats in the same household.
Most of the cats lived in households with 2 or
more humans (n = 18). Fifteen cats lived with other
cats; 11 lived in 2-cat households, and 4 lived in house-
holds with 3 or more cats. Few cats (n = 3) with OCD
had dogs in their household.
Training for dogs—Most dogs in this study had
what is considered to be basic training of some kind; 6
(5.9%) attended puppy kindergarten, 20 (19.6%)
attended basic group lessons, 10 (9.8%) attended
advanced group lessons, 17 (16.7%) had a private
trainer come to their house, and 3 (2.9%) were sent to
a private trainer.
Client compliance with treatment—Only 3% of
canine clients admitted to performing none of the
behavior modification. For 17% of the patients, com-
pliance data were unavailable. Sixty-three percent of
the clients either complied extensively (38%) or con-
sistently (25%). Twenty percent complied intermittent-
ly. Client compliance for treatment in cats was also
Treatment outcomes for dogs and cats were calcu-
lated (Fig 3 and 4). Percentage frequencies of dogs
with large decreases in intensity and dogs with large
decreases in frequency of behavioral problems were
significantly associated (Cochran-Mantel Haenzel test
statistic G
= 59.87; df = 1; P < 0.001). Other out-
comes included unknown (14 dogs were lost to follow-
up), small increase in intensity but a large decrease in
frequency of episodes (n = 1), death unrelated to OCD
(1), euthanasia for OCD (1), and euthanasia for rea-
sons unrelated to OCD (8).
Efficacy of medication—Of the 103 dogs in this
population, 84 were treated with 1 or more drugs.
Nineteen clients declined a drug treatment option for
their dog. There were sufficient data only to compare
the relative success rates for amitriptyline and
clomipramine (Table 1). The observed success rate for
clomipramine (0.83) was significantly greater than that
(0.59) for amitriptyline (log likelihood ratio test statis-
tic G
= 6.03; P < 0.05).
Duration of treatment—Dogs for which complete
information was available (n = 80) were treated for a
mean of 14.1 months, a median of 12 months, and a range
of 6 to 78 months. Cat data were insufficient for analysis,
but the range of continuous treatment was 2 to 4 months.
All cats from which medication was withdrawn (n = 9)
relapsed and drug treatment was reinstated.
Affected relatives—Clients knew whether rela-
tives were also affected with some form of OCD for
only 30 of the 103 dogs in this study; 15 dogs had
1448 Scientific Reports: Retrospective Study JAVMA, Vol 221, No. 10, November 15, 2002
Figure 3—Outcomes for 103 dogs treated for OCD. SDI = Small
decrease in intensity of OCD ( 50%). LDI = Large decrease in
intensity (> 50%). SDF = Small decrease in frequency of OCD
behavior ( 50%). LDF = Large decrease in frequency (> 50%).
S = Stopped OCD behavior completely. NC = No change.
Figure 4—Outcomes for 20 cats treated for OCD.
Figure 3
for key.
affected relatives and 15 did not. Of the 15 dogs with
affected relatives, 7 had 1 known affected relative (3
male littermates, 3 sires, and 1 dam), 7 had 2 known
affected relatives (female littermate-male littermate,
sire-male offspring, sire-other, grandsire-other, dam-
male littermate, dam-second degree relative), and 1
had 3 known affected relatives. Only 3 clients with cats
knew about affected relatives, and only 2 of these defi-
nitely had an affected relative (1 sire, 1 offspring).
Concurrent behavioral diagnoses—Seventy-seven
(74.8%) dogs had concurrent behavioral conditions, as
determined via published diagnostic criteria.
three (32.0%) dogs met the criteria for a diagnosis of
attention-seeking behavior (eg, excessive solicitation
and neediness), 29 (28.2%) met the criteria for a diag-
nosis of dominance or impulse-control aggression, 23
(23.3%) met the criteria for a diagnosis of separation
anxiety, and 16 (15.5%) met the criteria for a diagnosis
of generalized anxiety disorder. Thirty other miscella-
neous behavioral and medical diagnoses were also
noted. There was no association between duration that
the dog had been affected before treatment and the
number of concurrent behavioral diagnoses (r = 0.13;
P = 0.23). Because many dogs in this study had multi-
ple concurrent behavioral diagnoses, the sample sizes of
each diagnostic combination were insufficient to deter-
mine whether the associations were random, as has
been performed elsewhere.
The data were also insuffi-
cient to assess whether dogs that had been affected
longer had more intense or more frequent signs of
OCD, compared with dogs affected for a short period.
In contrast with dogs, only 9 of 23 (39.1%) cats
met the criteria for concurrent behavioral diagnoses, a
difference that was significant (log likelihood ratio test,
= 10.04; P < 0.05). In contrast with dogs, most of
the concurrent behavioral diagnoses were associated
with elimination disorders; 3 cats also sprayed, 2 cats
urine-marked without spraying, 1 cat marked with
feces, and 1 cat had a substrate aversion to the litter.
Only 1 cat met the criteria for separation anxiety, a
major concurrent diagnosis in dogs.
Stereotypic behaviors may or may not be associat-
ed with OCD.
Differential diagnoses for other
behavioral conditions in which the nonspecific signs
associated with OCD can occur include environmental
causes, management, humane considerations (eg,
those involving understimulation, neglect, or excessive
confinement), separation anxiety, attention-seeking
behavior, generalized anxiety, and hyperactivity.
Obsessive-compulsive disorder in all species is
characterized by repetitive, ritualistic behaviors, in
excess of any required for normal function, the execu-
tion of which interferes with normal, daily activities
and functioning. Inherent in this description is a
behavior that is exaggerated in form as well as dura-
tion. The diagnostic criteria employed here have dual
advantages. First, they permit separation of nonspecif-
ic signs from diagnostic criteria. This allows the non-
specific signs to be used to evaluate changes in the con-
dition and to further describe populations afflicted
with different manifestations of the condition.
Second, they do not require definition or assessment of
underlying motivational states, which is difficult to
accomplish in a meaningful manner in other species.
It appears that dogs, as do humans, may perceive
that their behaviors are abnormal and control their
behaviors to the extent that the behavior is performed
only minimally, or not at all, in the presence of others.
Dogs who flank suck or tail chase may, after frequent
reprimands and corrections, remove themselves from
view and then commit the behavior elsewhere. Upon
approach, the behavior ceases, only to begin again
when no one is watching or when the animal removes
itself from view. Results of this study support the exis-
tence of this evasive behavior pattern. If the desire to
perform the behavior is present, despite restraint
because of punishment, training, or physical incarcer-
ation, the condition is present. The key is that if such
control is removed and the animal can commit the
behavior, it will commit the behavior. Ignoring this
crucial point will result in underdiagnosis of OCD and
underestimation of its frequency in canine and feline
The presence of this and other cognitive compo-
nents suggests that the problem is rooted at a higher
level than the behavior alone may indicate (ie, a
Doberman Pinscher may be flank sucking, but not
because anything is wrong with its flank). Such exam-
ples support the contention that obsessions are a valid
component of OCD. We evaluate obsessions in
humans by asking them about repetitive, invasive
It is inappropriate to apply a criterion (eg,
assessment that relies on a verbal response) to 1
species that has a divergent phylogeny (eg, nonverbal)
that prohibits the use of that tool or criteria.
extent to which the patients in our study focused on
their behaviors, avoided those who sought to interfere
with them, and were avoided by clinically normal or
unaffected canine and feline housemates strongly sug-
gests that a cognitive component was present, albeit
difficult to assess.
Obsessive-compulsive disorder in humans fre-
quently appears in adolescence, at the onset of social
JAVMA, Vol 221, No. 10, November 15, 2002 Scientific Reports: Retrospective Study 1449
Table 1—Drug treatment and evaluation of success versus fail-
ure in 89 dogs and 20 cats with obsessive-compulsive disorder
No. of No. of Probability
Drug Successes Failures of success
32 22 0.593
30 6 0.833
8 1 0.889
1 1 0.500
1 0 1.000
3 0 1.000
1 2 0.333
1 0 1.000
1 0 1.000
1 0 1.000
3 0 1.000
*Used in combination with clomipramine to treat signs of panic. †Used for
pruritus associated with lesion caused by grooming in cats. ‡Used for pruri-
tus associated with lesions caused by grooming in dogs. §For treatment of
putative intervertebral disk disease. IIUsed in combination with amitriptyline
(2 animals) and clomipramine (1 animal) for signs of panic.
maturity, and continues through midlife. In dogs and
cats, OCD also appears during this indistinct period of
social maturity (range for dogs, 12 to 36 months;
mean, approx 18 to 24 months; range for cats, 24 to 48
months; mean, approx 30 to 36 months)
and if left
untreated, whether by behavioral or pharmacologic
intervention, it worsens. Given the relatively early age
at which this condition develops and the probability of
profound deterioration when left untreated, young ani-
mals should be routinely screened for OCD and treat-
ed appropriately early. Dogs and cats from families
with a history of OCD should be carefully watched for
its appearance, albeit possibly in a different form than
that of their relatives.
In this study, 10 of the 23 affected cats had signs of
their particular form of OCD after some physical trau-
ma or social upheaval, and the OCD in these cats may
have occurred concomitant with intercat aggression or
elimination problems. Siamese cats were ranked as the
second most common breed in this study. Although
this does not differ substantially from their rank in the
overall hospital population (3), it is dramatically dif-
ferent from the breed rank in our Behavior Clinic pop-
ulation (22), suggesting that when a Siamese cat is
evaluated because of a behavioral problem, the behav-
ior is likely associated with OCD. Siamese cats were
most often involved in ingestion of fabric, supporting
other findings regarding increased prevalence of OCD
in Oriental-breed cats,
but there were too few mem-
bers of each breed to reach breed-related conclusions.
It is interesting that the only Bengal cat in the study
population had self-mutilation and urine marking.
These are both anxiety-related conditions and may
have some association with the relatively recent
domestication of this breed. Most cats affected with
OCD had self-mutilation or excessive grooming. No
cats were reported to have signs of hallucinating; how-
ever, hallucinations may have been associated with tail
chasing. Most owners of these cats reported that the
cats acted as if something was on or near the cat’s tail
and that the cat was either trying to chase this entity or
escape it. Accordingly, feline hallucinations may not
have been adequately identified in this study.
Unlike cats, few dogs had OCD after trauma or
social-situational distress or upheaval, and few had
concurrent behavioral diagnoses involving elimination
or social relationships with other dogs. These data sug-
gest that the behavioral characteristics, neuroanatomic
regions affected, and molecular and neurogenetic
mechanisms of OCD may differ for dogs and cats. Two
dogs had OCD after physical trauma. In both dogs, the
trauma consisted of abusive training (hanging by a
choke collar). That 2% of this population of dogs with
OCD was subject to such abuse should be of concern
to all veterinarians.
One pet-store dog had profound coprophagia, sug-
gesting that at some point coprophagia may have rep-
resented a nutritional strategy. Of the 103 dogs, few
(approx 10%) had a putative neurologic disorder,
physical condition, or potentially painful disorder
associated with OCD, which could either be primary or
secondary to OCD. One dog had a diagnosis of irrita-
ble bowel syndrome, a diagnosis that may be simply a
nonspecific sign of an anxiety-related condition. This
finding supports the hypothesis that OCD in dogs is
based in some primary neurochemical or neurogenetic
dysfunction, and that the mechanisms driving OCD
may differ between dogs and cats.
Obsessive-compulsive disorder affects at least 2%
of the human population, and this is believed to be an
Some forms of OCD have a familial
genetic component
; however, most instances of
human OCD appear to be sporadic. It is important to
recognize that the development of specific animal
breeds and the practice of inbreeding within those
breeds suggest that the prevalence of OCD in dogs
could be higher than that reported for humans.
On the basis of client interviews and complaints,
OCD may be familial in Great Danes, German Short-
haired Pointers, German Shepherd Dogs, Bull
Jack Russell Terriers, Dalmatians, Bouvier de
Flanders, Salukis, Cairn Terriers, Basset Hounds, and
Soft-Coated Wheaten Terriers.
The strong correla-
tions between canine breeds and forms of OCD we
detected strongly suggest a genetic basis for OCD,
albeit, in part as the result of genetic limitations and
subsequent potential decreases in genetic heterogene-
ity associated with breed.
As is true for humans, first-degree relatives usual-
ly have a different form of OCD than the proband,
which supports the hypothesis of a heritable, neuro-
chemically variable basis for OCD. That 50% of the
dogs in this study for which familial data were known
had a relative affected with some form of OCD strong-
ly suggests 2 important points: certain breeds of dogs
appear to have a high prevalence of OCD, perhaps
higher than that in the human population, and a larg-
er proportion of canine relatives are affected than
appears true for humans. This strongly suggests a
genetic component for OCD in dogs.
Results of recent studies indicate that OCD in
humans is the result of dysfunction of genes involving
neurochemical and intracellular regulatory systems.
Similar complex regulatory systems that have a genet-
ic, heritable basis have also been reported for dogs
and may be involved in OCD.
Human OCD has been postulated to be caused by
aberrant serotonin metabolism.
Accordingly, treat-
ment has been directed at affecting serotonergic metabo-
lism; pharmacological agents used for treatment are fair-
ly specific and affect subclasses—primarily the 5-HT
class—of serotonin receptors. Neuropharmacologic
approaches to treatment have sought to address such reg-
ulatory abnormalities by augmenting serotonin through
the use of TCAs and SSRIs.
The key to the success of
the specific TCAs and SSRIs over other classes of med-
ication is that they use the same second messenger sys-
tems and transcription pathways that are used to develop
cellular memory (ie, learning).
While the best design for comparing drug efficacy
is a prospective, placebo-controlled, double-blind
study, other statistical comparisons can be made if cri-
teria for switching medications are consistent, as was
the case here. Such techniques are underused in veteri-
nary medicine, which is unfortunate since the funding
and large enrollment pools required for the former are
1450 Scientific Reports: Retrospective Study JAVMA, Vol 221, No. 10, November 15, 2002
seldom available. As is true for humans, dogs with
OCD respond well to the TCA, clomipramine,
and to the SSRI, fluoxetine.
Results of the study
reported here indicated that clomipramine was superi-
or for treatment of OCD in dogs, compared with
amitriptyline. The difference in efficacy is likely asso-
ciated with specificity for the serotonin 1A subtype (5-
) receptor of the parent compound and at least 1
of the intermediate metabolites that acts as a SSRI.
This specificity may also be responsible for the success
of fluoxetine in the treatment of some forms of
although our sample size was not sufficient to
test this hypothesis.
Adverse effects appear rare in canine patients; the
most common adverse effects have been gastrointesti-
nal disorders.
Use of TCAs is contraindicated in ani-
mals with a history of urinary retention and severe,
uncontrolled cardiac arrhythmias.
It is surprising that amitriptyline was at all effica-
cious (32/54 animals) in the treatment of OCD in our
study. Although not the drug of choice for treatment of
OCD in humans, this relatively nonspecific TCA may
sufficiently decrease nonspecific anxiety so that
patients can learn to change their behavior. At present,
we have no way to evaluate how advanced OCD is
when it is diagnosed in dogs and cats. Early signs may
go unnoticed. The success associated with treatment
with amitriptyline may reflect that some animals have
less severe forms of OCD and fewer comorbid diag-
noses. No animals with long-term OCD and multiple
concurrent behavioral diagnoses improved when treat-
ed with amitriptyline alone in this study.
In our study, 74.8% of the canine patients, but only
39.1% of the feline patients, had concurrent behavioral
diagnoses. When considered in light of the relative role
apparently played by environmental factors in OCD for
these 2 species and the divergent evolutionary and
domestication histories of dogs and cats, caution is
urged in assuming that OCD is mechanistically the
same in these 2 species. This finding could be fortu-
itous and lead us to a clearer understanding of a con-
dition that is multifactorial and has both genetic and
sporadic forms. Furthermore, the high rate of concur-
rent primary anxiety disorders (attention-seeking
behavior, separation anxiety, and generalized anxiety
disorder) in dogs affected with OCD suggests that as 1
anxiety-related condition progresses, other conditions
may represent manifestations of additional underlying
neurochemical and molecular changes.
Few dogs or cats in our study had complete ces-
sation of behaviors associated with OCD, although
most clients complied with the treatment protocols;
however, none became worse as a result of treatment
and only 1 dog and 1 cat were euthanatized because
of OCD. Treatment with medication (clomipramine)
and behavior modification was extremely successful;
however, mean canine treatment time was 14.1
months, and more than half of all canine patients
were treated for > 12 months. This is important
because the label instructions for clomipramine for
treatment of separation anxiety suggest a shorter
treatment period. There is considerable variation
between individual dogs in plasma concentrations. In
dogs, clomipramine reaches steady-state concentra-
tions in 3 to 5 days, peak plasma concentrations are
attained in approximately 1 to 3 hours, the half-life of
the parent compound is 1 to 16 hours, and the half-
life of the active intermediate metabolites is 1 to 2
These data suggest that dogs may require
higher dosages or more frequent dosing than do
humans treated with such medications. Should the
medication be discontinued, relapses occur in many
Signs also worsened or became more pro-
nounced in stressful or anxiety-inducing circum-
stances for some patients in our study. Use of
clomipramine to treat OCD in animals is extralabel
usage in the United States.
Available from corresponding author upon request.
Clomicalm, Novartis Animal Health, Greensboro, NC.
SAS, SAS Institute Inc, Cary, NC.
Amitriptyline, Stuart, Wilmington, Del.
Clomipramine, Ciba-Geigy, Summit, NJ.
Fluoxetine, Eli Lilly & Co, Indianapolis, Ind.
Buspirone, Mead Johnson Pharmaceuticals, division of Bristol-
Myers Squibb Co, Princeton, NJ.
Alprazolam, Upjohn, New York, NY.
Hydroxyzine, Roering, New York, NY.
Doxepin, Roering, New York, NY.
Sertraline, Pfizer Animal Health, Groton, Conn.
Pentazocine, Winthrop, NC.
Diazepam, Roche, New York, NY.
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1452 Scientific Reports: Retrospective Study JAVMA, Vol 221, No. 10, November 15, 2002
... Health issues and pain can be underlying causes as well 2,14,18 . Furthermore, comorbidity between repetitive behaviours and other behavioural problems have been reported in dogs and other animals 7,13,14,16,18 . Additionally, heritable contributions have been demonstrated by the observed breed-specificity of repetitive behaviours, as well as recent gene discoveries 14,[19][20][21][22] . ...
... Canine compulsive disorder, which is characterized by abnormal repetitive behaviours has been proposed as a model for human OCD 27,28 , as a growing body of evidence shows many similarities between human and canine compulsions. These include early age of onset 13,14,29,30 , behavioural inflexibility resulting from executive function impairment 31-33 , structural abnormalities in the brain 34,35 , increased blood cholesterol levels 36 , imbalanced serotonergic and dopaminergic pathways 26,37 , and similar pharmacological and non-pharmacological interventions for treatment 10,36,38,39 . In dogs, fluoxetine 39 and clomipramine 13,36,38 are used to treat compulsive disorders with repetitive behaviours, and both are commonly used to treat human OCD as well. ...
... However, the equivalence of canine and human compulsions has been challenged 40 . Different forms of OCD and canine compulsive disorder probably involve some different factors, but it can be suggested that different compulsions also overlap and share biological etiology and common genetic factors 13,14,16 . ...
Full-text available
Repetitive behaviour ranges from variants of normal repetitive behaviours to abnormal repetitive behaviours. The domestic dog spontaneously performs different repetitive behaviours, which can be severe and impair the quality of life and the dog-owner relationship. We collected comprehensive behavioural questionnaire data from almost 4500 Finnish pet dogs and studied the effect of several demographic, environmental, and behavioural factors on canine repetitive behaviour with logistic regression. We replicated findings from previous studies by revealing comorbidity between repetitive behaviour and behavioural factors aggressiveness, hyperactivity/impulsivity, and inattention. We also found a novel association between repetitive behaviour and the owner’s dog experience. In addition, we showed that repetitive behaviour is more common in dogs that live without conspecifics, dogs that were given a low amount of exercise, dogs that lived in larger families, young dogs and elderly dogs, and neutered dogs. Finally, we identified breed differences in repetitive behaviour, suggesting that some breeds are more vulnerable to repetitive behaviour and indicate a genetic susceptibility. As abnormal repetitive behaviour can considerably worsen the well-being of dogs and impair the dog-owner relationship, a better understanding of the environmental, lifestyle, and molecular factors affecting canine repetitive behaviour can benefit both dogs and humans.
... In addition, the inability to avoid fearful situations may lead to chronic distress (Levine, 2008). Repetitive behaviors, such as excessive grooming, are less common but may be harmful to cats: these can include frantic licking and self-mutilation, for example, pulling out hair, which leads to bald patches (Overall and Dunham, 2002;Bennett and Khan, 2021). ...
... Aggression caused by fear is a common phenomenon in cats (Amat and Manteca, 2019), which could explain the first connection. Excessive grooming can be induced by stress or trauma (Overall and Dunham, 2002;Luescher, 2003) and fearful cats may be more vulnerable to it, which could explain the second connection. ...
Full-text available
Problematic behaviour is a remarkable welfare issue in cats (Felis catus), as it is one of the most common reasons for relinquishment. The probability of developing problematic behaviours is likely influenced by several variables, but these remain little studied. In this study, we examined the associations of fearfulness, aggression toward humans, and excessive grooming with nearly thirty variables in a survey data set of over 3200 cats. To identify the most important variables influencing these behaviours, we used generalized linear models. All behaviours were associated with each other suggesting comorbidity between problematic behaviours. Breed and several environmental variables were also associated with behaviours. Poor socialization to humans and a history of being a rescue cat were associated with higher fearfulness, indicating that proper socialization of kittens is beneficial for avoiding fear-related problematic behaviours. Overall, our study highlights the complexity of three problematic behaviours in cats.
... Therefore, stopping positive punishment may have alleviated the stress-overgrooming cycle, thus limiting the interpretation of results of both groups while it is not reported how positive punishment by owners was distributed across the clomipramine group and the placebo group. It should be noted that one before and after study (Seksel & Lindeman, 1998), two case series (Overall & Dunham, 2002;and Sawyer et al., 1999) and one case study (Talamonti et al., 2017) reported that implementation of a behavioural and environmental modification plan along with clomipramine provided a sustained reduction in overgrooming among cats with psychogenic alopecia. Although subjective assessment by owners may have overestimated the positive effects of the treatment combination, these non-controlled study findings suggest Mertens et al. (2006) cannot be interpreted without consideration of the environmental changes that may have occurred for some cats enrolled in the study. ...
... Therefore, further research with randomised, double-blind controlled trials and limitation of confounding factors is needed to substantiate the efficacy of clomipramine alone or in addition to behavioural / environmental therapies. It should be indeed noted that various non-controlled studies (Overall & Dunham, 2002;Sawyer et al., 1999;Seksel & Lindeman, 1998;and Talamonti et al., 2017) suggested that if a behavioural and environmental modification plan was set up alongside the clomipramine treatment in cats with psychogenic alopecia the exhibition of overgrooming might diminish or even discontinue. ...
Full-text available
PICO question In cats with psychogenic alopecia, is overgrooming reduced by the use of clomipramine compared to untreated cats? Clinical bottom line Category of research question Treatment The number and type of study designs reviewed One pseudo-randomised controlled study Strength of evidence Weak Outcomes reported Effect of clomipramine using owner report of number, intensity, and / or duration of grooming episodes, owner reported clinical improvement, and veterinary measured alopecia, extent of tissue damage, and hair regrowth Conclusion The only controlled study found no evidence that clomipramine alone is effective in reducing grooming episodes, alopecia, or improved hair regrowth. Further research with randomised, double blind controlled trials and limitation of confounding factors is required to determine the efficacy of clomipramine alone or in addition to behavioural / environmental therapies How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.
... In a changing environment, genes interact with the environment and with past experiences, thus contributing to the modification of the behavioral phenotype [5]. Evidence supports a genetic component for psycho-behavioral traits in dogs such as anxiety/fear, noise phobia, human aversion, obsessive-compulsive disorder, predatory behavior, and at least 2 types of aggression: impulse/control and conspecific [6][7][8][9]. Moreover, the psycho-pathological outcome from early trauma may have, at least in part, a hereditary basis [10]. ...
... Another factor found to influence paw preference in dogs is age, with older dogs showing a stronger right paw bias than younger dogs (Laverack et al. 2021). Dog's pawedness is more defined, and therefore easier to identify, once the dog is closer to social maturity (Overall and Dunham 2002;Batt et al. 2008). ...
Full-text available
Handedness has proven to be the most effective and least intrusive measure of laterality in many species. Several studies have investigated paw preference in dogs ( Canis familiaris ) without considering the potential impact that owner’s handedness may have on it, despite dogs being a domesticated species. The aim of this study was to investigate whether owner handedness influences paw preference in their dogs. Sixty-two dogs had their paw preference tested using a Paw Task and a Reach Task in their home over 10 days, recorded by their owners. Interestingly, it was found that left-handed owners were more likely to own a dog with a left paw bias, and right-handed owners were more likely to own a dog with a right paw bias. In the Paw Task, the hand presented to a dog did not significantly predict which paw the dog lifted in response. Furthermore, it was found that females displayed a right paw bias at all age groups. However, males had a left paw bias in puppyhood and right paw bias in older age groups. We conclude that owner handedness influences paw preference in dogs, and it should be considered when suitably pairing dogs to potential owners, especially in assistance work.
... Bath (36,37) Hospital visit (38)(39)(40), handling and restraint practices (28,29) Confinement (27,41) Novel environment (e.g., entering shelter) (21,42,43) New socialization, such as group housing (21,42) Prolonged/chronic stress Sickness behavior, (e.g., vomiting) Changed caretaking routine (24,32,33,44) Anorexia Long-term sheltering (31) House soiling problem (45,46) In appropriate elimination (1,47) Social conflict, blocked access to the litterbox (1), changes related to litter (47,48) Chronic disease, such as feline idiopathic cystitis (49) Fecal marking (1) Outdoor and indoor social conflicts (1) Urine marking (1,50) Lower urinary tract disorders (51), substantial changes in the social and physical environment (1,49,50,52) Depression-like symptom (e.g., inactivity) Long-term sheltering (53) Aggression (2,(54)(55)(56) Social conflicts (2,54,57), high housing density (43), co-residence with dogs (58) and other cats (59), long-term sheltering (53) Stereotypic behavior (e.g., over grooming or self-mutilation, tail biting, and obsessive vocalization) (60,61) Stress from chronic disease, environmental and social conflict (1, 60, 61) Frustration from limited outdoor access (58,61,62) concealed areas (i.e., hiding), reduced activity level and diversity, anxious body postures, and aggression are indicative of acute stress in cats (8,24,26). Noteworthy, coping style (e.g., reactive or proactive) was reported to impact behavioral responses of individual cats to stressful events or environments such as acute cage confinement (41). ...
Full-text available
Domestic cats are descended from solitary wild species and rely heavily on the olfaction system and chemical signals for daily activities. Cats kept as companion animals may experience stress due to a lack of predictability in their physical or social environment. The olfactory system is intimately connected to the brain regions controlling stress response, thus providing unique opportunities for olfactory strategies to modify stress and related behavioral problems in cats. However, the olfactory intervention of stress in cats has been mainly focused on several analog chemical signals and studies often provide inconsistent and non-replicable results. Supportive evidence in the literature for the potentially effective olfactory stimuli (e.g., cheek and mammary gland secretions, and plant attractants) in treating stress in cats was reviewed. Limitations with some of the work and critical considerations from studies with natural or negative results were discussed as well. Current findings sometimes constitute weak evidence of a reproducible effect of cat odor therapy for stress. The welfare application of an olfactory stimulus in stress alleviation requires a better understanding of its biological function in cats and the mechanisms at play, which may be achieved in future studies through methodological improvement (e.g., experiment pre-registration and appropriate control setting) and in-depth investigation with modern techniques that integrate multisource data. Contributions from individual and environmental differences should be considered for the stress response of a single cat and its sensitivity to olfactory manipulation. Olfactory strategies customized for specific contexts and individual cats can be more effective in improving the welfare of cats in various stressful conditions.
Background: Acral lick dermatitis is defined as self inflicted skin disorder in dogs which induces localized alopecia and fibrotic lesion due to repetitive licking or chewing at the same ‘site most commonly near carpus or hock areas. Methods: The present study was carried out to investigate the approach to the management of various etiologies associated with ALD in dogs. A total of 30 dogs that were diagnosed with acral lick dermatitis (ALD) were rated on the day 0 of theirvisit to the hospital on the basis of three clinical scalesie; ALD severity scale, clinical global impression (CGI) and likert scale. Assessment and weekly rating of the ALD lesion was done during the entire treatment trial. Result: Dogs positive for psychogenic primary triggers were randomly divided in Group 1 (n=9; 47.36%) and Group 2 (n=10; 52.63%). Dogs in group 1 were treated with fluoxetine and dogs in group 2 were treated with clomipramine. Whereas dogs diagnosed with organic triggers were treated empirically. Dogs treated under group 1 exhibited significant difference (p less than 0.05) in the licking and ALD score values at the end of the trial, however, CGI score values were found to be non significant (p greater than 0.05) with mean recovery in 24±2 days and recurrence rate of 44.44% after mean 105±47 days of their treatment completion. 33.33% dogs were also reported with adverse effects of drug as drowsiness in group 1. Dogs treated under group 2 exhibited significant difference (p less than 0.05) in pre and post treatment values of all 3 scores (licking score, ALD score and CGI score) at the end of the trial with mean recovery in 41±5 days and 55.55% cases were reported with signs of reoccurrence after mean 37±21 days of their treatment completion. Total 2(20%) dogs out of ten were presented with adverse effects; 1(10%) with loss of appetite and 1(10%) was reported with vomiting. Both clomipramine and fluoxetine are effective in treating psychogenic triggers of ALD. However, fluoxetine helps in early recovery with lesser recurrence rates whereas clomipramine having better recovery rate with fewer side effects.
Behavior can change as a result of medical problems or physiological changes, and behavior changes are likely to be the first signs of stress, disease, and poor welfare in any animal. If shelter operations, behavior, and/or medical staff identify behaviors that may have an underlying medical cause, they can be addressed immediately, relieving suffering and increasing the adoptability of the animal. Conversely, if medical conditions that cause or exacerbate problematic behaviors are missed, time may be wasted on training or attempted behavior modification, thus prolonging suffering and time spent in the shelter. Only by safeguarding both physical and emotional health can we improve overall quality of life for animals in our care, facilitate their placement in homes, and help prevent their return to the shelter.
Behavioural disease is one of the leading reasons for euthanasia in shelter dogs and cats. Information acquired via a survey of veterinarians (n = 59) was used to understand the way canine and feline behaviour problems are viewed and managed by nonshelter, small animal general practice veterinarians. Participants (20%, n = 12) felt that the following diseases were more of a welfare issue than behaviour problems: food sensitivity, osteoarthritis, puppy/kitten farms, skin disease, nutritional disease, parasitic disease, dental disease, obesity, in‐breeding, over‐population, neoplasia, greyhound racing, hyperthyroidism and renal disease. Behaviour problems in dogs and cats were not ranked in the top four welfare problems by 40% (n = 23) of respondents. Behaviour case follow‐up was poorer than physical health case follow‐up. Respondents (20%, n = 12) felt that veterinarians should ‘possibly’ be able to identify behaviour problems in dogs and cats, and 54% (n = 32) felt that this was ‘absolutely’ their professional responsibility. Twelve percent (n = 7) would reschedule behaviour appointments that had been booked in for them. Behaviour was more likely to be seen as a welfare issue by more experienced veterinarians and also, those with shelter experience. Half of respondents felt reluctant to discuss behaviour problems with clients because of deficiencies in behaviour knowledge. Eighty percent (n = 47) felt their education equipped them poorly or extremely poorly in dealing with behaviour problems in dogs and cats. Consideration should be given for the inclusion of adequate behavioural medicine content in veterinary medicine curriculum to allow for graduates to possess a basic level of training and competency in this discipline.
Objectives: To determine the effectiveness of fluoxetine hydrochloride at fixed doses of 20 mg/d, 40 mg/d, and 60 mg/d in patients with obsessive-compulsive disorder (OCD) and to evaluate its safety.Methods: Fixed-dose fluoxetine hydrochloride (20 mg/d, 40 mg/d, 60 mg/d) was compared with placebo in two randomized, double-blind, parallel, 13-week trials of identical design in 355 outpatients with OCD aged 15 to 70 years (DSM-III-R criteria; 1 year's duration or longer; depression secondary if present).Results: Fluoxetine (all doses) was significantly (P±001) superior to placebo on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) total score (mean baseline-to-end—point decrease, 4.6,5.5, and 6.5 vs 0.9, respectively, studies pooled) and other efficacy measures (P±01). A trend suggesting greater efficacy at 60 mg/d was observed. Most patients (79.2%) completed the study. Eight adverse events were statistically significantly more frequent with fluoxetine and one, with placebo. For some events, incidence tended to increase with increasing dosage; however, few patients discontinued treatment for any single event.Conclusion: Fluoxetine was associated with a statistically significant reduction in OCD severity, including time engaged in obsessional and/or compulsive behaviors. Adverse events infrequently led to study discontinuation.
• The prevalence of obsessive-compulsive disorder was measured in five US communities among more than 18500 persons in residential settings as part of the National Institute of Mental Health (Bethesda, Md)—sponsored Epidemiologic Catchment Area program. Lifetime prevalence rates ranged from 1.9% to 3.3% across the five Epidemiologic Catchment Area sites for obsessive-compulsive disorder diagnosed without DSM-III exclusions and 1.2% to 2.4% with such exclusions. These rates are about 25 to 60 times greater than had been estimated on the basis of previous studies of clinical populations.
Recent studies have begun to characterize the actions of stress and antidepressant treatments beyond the neurotransmitter and receptor level. This work has demonstrated that long-term antidepressant treatments result in the sustained activation of the cyclic adenosine 3', 5'-monophosphate system in specific brain regions, including the increased function and expression of the transcription factor cyclic adenosine monophosphate response element-binding protein. The activated cyclic adenosine 3', 5'-monophosphate system leads to the regulation of specific target genes, including the increased expression of brain-derived neurotrophic factor in certain populations of neurons in the hippocampus and cerebral cortex. The importance of these changes is highlighted by the discovery that stress can decrease the expression of brain-derived neurotrophic factor and lead to atrophy of these same populations of stressvulnerable hippocampal neurons. The possibility that the decreased size and impaired function of these neurons may be involved in depression is supported by recent clinical imaging studies, which demonstrate a decreased volume of certain brain structures. These findings constitute the framework for an updated molecular and cellular hypothesis of depression, which posits that stressinduced vulnerability and the therapeutic action of antidepressant treatments occur via intracellular mechanisms that decrease or increase, respectively, neurotrophic factors necessary for the survival and function of particular neurons. This hypothesis also explains how stress and other types of neuronal insult can lead to depression in vulnerable individuals and it outlines novel targets for the rational design of fundamentally new therapeutic agents.