ArticlePDF Available

Abstract and Figures

Sixty-seven dogs that showed signs of distress when separated from their owners (destructiveness, excessive vocalisation and house soiling) and hyperattachment were used in a randomised, blind trial to assess the potential value of a dog-appeasing pheromone in reducing the unacceptable behaviours. For ethical reasons, there was no placebo group and the effects of the pheromone were compared with the effects of clomipramine which is regularly used to treat this type of problem. The undesirable behaviours decreased in both groups, but the overall assessment by the owners indicated that there was no significant difference between the two treatments, although there were fewer undesirable events in the dogs treated with the pheromone, and the administration of the pheromone appeared to be more convenient.
Content may be subject to copyright.
The Veterinary Record, April 23, 2005
SEPARATION-RELATED behaviour problems in dogs
occur only when the dog is separated from or denied access
to its owner. Typically, the main complaints are destructive-
ness, excessive vocalisation and house soiling, but some dogs
may hyperventilate, vomit, salivate, urinate or have diar-
rhoea. Several causes have been suggested (Voith and
Borchelt 1985, McCrave 1991, Overall and others 1999,
Takeuchi and others 2000). Until recently, the term ‘separa-
tion anxiety’ was used as a synonym for ‘separation-related
behaviour problems (Heath 2002), but it is now recom-
mended that the term is used only to describe dogs with
undesirable behaviours motivated by anxiety (Appleby and
Pluijmakers 2003). In 1982, Borchelt and Voith proposed
that one explanation for this problem was the strong social
bond between the dog and its owner, and other authors have
described the signs of a strong attachment between some
dogs and their owners; for example, they may follow the
owner from room to room (McCrave 1991), they may avoid
being left alone in a room (McBride and others 1995) and
they may sleep close to the owner (Jagoe and Serpell 1995).
The terms ‘hyperattachment’ and ‘overattachment’ are
used by some authors to describe these excessive contact-
seeking behaviours (Pageat 1995, Takeuchi and others 2000,
Flannigan and Dodman 2001, Appleby and Pluijmakers
2003). Behavioural data have shown that the typical signs of
hyperattachment are strongly correlated with the signs of
distress in dogs suffering from separation-related behaviour
problems (Gaultier 2001). It is necessary to consider the
dog’s behavioural signs carefully to determine an accurate
causal diagnosis; otherwise, any proposed treatment
may focus only on the disruptive behaviours, and the dis-
tress underlying these behaviours may remain untreated
(McCrave 1991, Pageat 1995).
Separation-related behaviour problems are the second
most common behavioural disorder recorded in dogs at refer-
ral behavioural practices, coming just after aggression
(Borchelt and Voith 1982, Wright and Nesselrote 1987,
Landsberg 1991, McCrave 1991, Pageat 1995, Overall 1997,
Simpson 2000, Gaultier 2001). The consequences of house
soiling and destructiveness on the home and the effects of
vocalisation on the neighbourhood often upset owners and
may lead them to surrender their dog to a shelter if a quick
solution is not found (Van der Borg and others 1991, Lesaine
1996). Most of the undesirable behaviours are also significant
in terms of the dog’s own welfare, and relieving the distress of
affected dogs should therefore be a priority.
There are now many behavioural plans and pharmaco-
logical treatments which appear to be effective (Tuber
and others 1982, Pageat 1995, O’Farrell 1997, Overall 1997,
Podberscek and others 1999, Blackwell and others 2002).
Among these protocols, only the use of behavioural therapy
combined with clomipramine (a psychotropic drug which is
a combined serotonin and noradrenalin reuptake inhibitor)
has been formally validated in randomised, placebo-con-
trolled studies (Petit and others 1999, Podberscek and oth-
ers 1999, King and others 2000). This combination will be
referred to as the ‘reference treatment’. It has been shown that
the reference treatment increases the rate at which dogs
improve or resolve (63 per cent from day 28 onwards) in com-
parison with dogs treated by a behaviour modification plan
alone (29 per cent) (King and others 2000). But drugs may
have drawbacks, including undesirable side effects, and they
may be difficult to administer regularly; these drawbacks can
be a real obstacle to maximal compliance.
A group of pheromones, secreted in the mammary area
shortly after parturition, was first identified by Pageat (2000).
Because these pheromones seem to have an appeasing effect
on both young and adult animals they were called ‘appeasines
(Pageat and Gaultier 2003). Dog-appeasing pheromone
DAP; Ceva Santé Animale) is a synthetic analogue of this
mixture of esters of fatty acids produced by the sebaceous
glands in the intermammary sulcus of bitches. It can be deliv-
ered by means of an electric diffuser (Shepperd and Mills
A placebo-controlled trial may be considered unethical in
accordance with the recent guidance on statistical principles
for trials (Anon 1999). In this case, the synthetic pheromone
was compared with clomipramine, the efficacy of which has
been established in well designed trials by Petit and others
(1999) and King and others (2000).
Type of comparison
The lack of any placebo group makes external validation nec-
essary. To this end, the active control trial should have the
same design features (primary variables, dose of active com-
parator, eligibility criteria, and so on) as previously con-
ducted superiority trials (Anon 1999, Steinijans and others
2000). The chi-squared test and Mann-Whitney U test have
been used to analyse secondary parameters. The secondary
Papers & Articles
Veterinary Record (2005)
156, 533-538
E. Gaultier, DVM, MSc,
L. Bonnafous, DVM,
L. Bougrat, MSc,
C. Lafont, MSc,
P. Pageat, DVM, PhD,
Phérosynthèse, Le Rieu
Neuf, 84490, Saint-
Saturin-les-Apt, France
Comparison of the efficacy of a synthetic
dog-appeasing pheromone with
clomipramine for the treatment of
separation-related disorders in dogs
E. Gaultier, L. Bonnafous, L. Bougrat, C. Lafont, P. Pageat
Sixty-seven dogs that showed signs of distress when separated from their owners (destructiveness,
excessive vocalisation and house soiling) and hyperattachment were used in a randomised, blind trial to
assess the potential value of a dog-appeasing pheromone in reducing the unacceptable behaviours. For
ethical reasons, there was no placebo group and the effects of the pheromone were compared with the
effects of clomipramine which is regularly used to treat this type of problem. The undesirable behaviours
decreased in both groups, but the overall assessment by the owners indicated that there was no significant
difference between the two treatments, although there were fewer undesirable events in the dogs treated
with the pheromone, and the administration of the pheromone appeared to be more convenient. on December 26, 2012 - Published by veterinaryrecord.bmj.comDownloaded from
The Veterinary Record, April 23, 2005
parameters assessing efficacy were analysed on the results
from the animals which fulfilled the full protocol, and
the other secondary parameters (demographic differences
and tolerability) were analysed on the results from all the
Recruitment of subjects
The dogs were recruited at veterinary clinics in France, Italy,
Spain and Switzerland, all of which had a significant behav-
ioural referral case load, and the selection criteria were simi-
lar to those applied in the trials by Petit and others (1999) and
King and others (2000) (Table 1). The dogs were recruited
after a behavioural examination, in order to exclude dogs with
organic medical problems, and after a detailed behavioural
questionnaire assessed by the veterinarian. If the dog fulfilled
the criteria, it was randomly assigned to a treatment group,
and after having obtained the written consent of the dog’s
owner, the behavioural modification plan – the same as that
in the trials by Petit and others (1999) and King and others
(2000) – was presented to the owner.
The dogs were assigned to the two treatment groups at ran-
dom. The pheromone was administered through a reservoir-
type electrical diffuser, containing 30 ± 0·2 g of a 2 per cent
solution of the synthetic pheromone in paraffin oil. Ideally,
the diffuser had to be installed in the room in which the dog
tended to spend most of its time during the day, and to which
it had access in the absence of its owners. If this was not pos-
sible it had to be installed in a part of the house in which the
dog was allowed to remain when its owner was absent.
Clomipramine was administered orally twice a day in capsules
supplying 1·0 to up to 2·0 mg/kg bodyweight, equivalent to
between 2 and 4 mg/kg/day. Each capsule contained equal
parts of a mixture of clomipramine hydrochloride and med-
icinal grade lactose. A placebo diffuser, containing a mixture
of two mineral oils chemically similar to those used for the
pheromone solution, was installed in the houses of the dogs
receiving clomipramine, to preserve the blind nature of the
trial. The dogs in the pheromone group similarly received
placebo capsules containing only lactose. The random assign-
ments of the treatments were balanced every six cases by each
investigator. Any other kind of treatment that could modify
the behaviour of the dog or its gastrointestinal and urinary
functions was forbidden during the trial.
Trial period
The treatments were administered for a mean period of 28
days (with a minimum of 24 days and a maximum of 33
days). This period was chosen for two main reasons. First,
owners with a problem dog often ask for a quick improve-
ment, and to be considered a relevant therapy any product
must therefore be effective in a short period and one month
was believed to meet this requirement. Secondly, the new
treatment should be assessed under conditions in which the
reference treatment shows its highest possible efficacy (Garbe
and others 1993, Anon 1999), and clomipramine reached its
highest efficacy after 28 days (King and others 2000). The
dogs were seen by the investigator for a veterinary and behav-
ioural examination on the day the treatment began (visit 1,
day 0) and 28 days later (visit 3). The owners were contacted
by telephone by the vet between day 12 and day 18, the day
of the second visit (visit 2).
Assessment criteria
Efficacy The overall efficacy of each protocol was assessed on
the basis of a variable integrating the owner’s and the vet’s
overall impression about the change in the state of the dog;
it therefore took into consideration not only the signs shown
during the owner’s absence but also the behaviour of the dog
when its owner was present. The variable was a scale of
ordered ratings of the change in the dog’s overall behaviour
between visit 2 or 3 and visit 1, in which the categories were
‘worse, ‘no change, ‘reduced’ and disappeared’. The primary
target signs shown during the owner’s absence were destruc-
tion, ‘vocalisation’ and ‘house soiling’, and they were rated
as ‘worse, ‘no change’, ‘reduced’, disappeared’ or ‘newly
appeared’, as compared with the baseline visit on day 0.
‘Disappeared’was defined as the total absence of the sign since
the last visit, ‘newly appeared’ as the appearance of the sign
since the last visit,‘worse and ‘reduced’were based on changes
in the frequency of the behaviour. Taking into account the
response of the owners to specific questions and the daily
monitoring form, the results were recorded and compiled by
the investigator. The monitoring form indicated how many
times and for how long the owner had been absent on each
day, and what the dog had done, in terms of destruction,
vocalisation and house soiling, during their absence. This
information helped the investigator to improve the objectiv-
ity of the overall assessment of efficacy.
The investigator also took into consideration ‘secondary
signs of distress’, including sleeping problems, excessive lick-
ing, feeding and drinking problems, gastrointestinal problems
and other behaviours such as over-reaction to stimuli, lack
of adaptation to changes, and reduced exploratory behaviour,
signs which could be evaluated objectively. Some of these
signs were shown not only in the absence but also in the pres-
ence of the owner. They were rated as either ‘present or
absent’ at each visit.
Tolerability The tolerability of the two treatments was eval-
uated by questioning the owner by phone at visit 2 and
directly at visit 3, and completed by a behavioural examina-
tion of the dog at visit 3. The frequency and severity of each
adverse sign was recorded.
Compliance At the beginning of the protocol, the investiga-
tor gave the owner the bottles containing the number of cap-
sules needed for the full treatment, that is 30 days plus three
days to cover unforeseen eventualities, and a diffuser con-
taining 30 ± 0·2 g of
DAP solution. For the clomipramine treat-
ment, compliance was assessed by comparing the number of
capsules returned, and hence the number administered, with
the number required for the effective duration of the treat-
ment. For the
DAP therapy, compliance was assessed by com-
paring the weight of the solution vaporised with the effective
duration of the treatment.
Statistical analysis
The Hauck-Anderson corrected classical procedure for inde-
pendent binary endpoints (Tu 1997) was used to assess the
one-way confidence in the treatment.
The statistical analysis used in non-inferiority trials is very
specific; its main characteristic is to specify a lower equiva-
Papers & Articles
Number Treatment
Category of dogs Clomipramine DAP Reason for exclusion
Excluded from 10 1 1 Loss of follow up before any control visit
full protocol 0 1 Loss of follow up after the first control visit
0 1 Withdrawal of owner consent
1 0 Other medical event
0 1 Other non-medical event
0 1 Breaking of blinding code after the first
control visit
2 2 Lack of efficacy
Full protocol 57 27 30
DAP Dog-appeasing pheromone
TABLE 1: Numbers of dogs that failed to adhere to the full protocol, and the reasons for their
exclusion, and the numbers that did adhere to the full protocol on December 26, 2012 - Published by veterinaryrecord.bmj.comDownloaded from
The Veterinary Record, April 23, 2005
lence margin. This margin ‘d’is the largest difference that can
be judged as being behaviourally acceptable and should be
smaller than the difference observed in superiority trials of
the active comparator (Anon 1999). When there is no con-
sensus in the field of the problem, the value of d is arbitrar-
ily determined as 0·2 (relative value) (Com-Nougue and
Rodary 1987, Bristol 1999). So, hypothesising that
should be better tolerated and easier to administer, the two
protocols would be considered for these practical purposes
to be equivalent if the
DAP efficacy results are unlikely to be
more than 20 per cent less than the reference treatment
For the primary variable (the overall assessment), ‘dis-
appeared’ and ‘reduced’ cases were rated as ‘success, and
‘worse and ‘no change as ‘failure. For all the other parame-
ters, a classical non-superiority approach was used.
Qualitative variables assessing destruction, vocalisation,
house soiling and secondary signs of distress were tested
with a two-tailed chi-squared test with P<0·05 considered
Twelve centres participated in the study, nine were in France,
one in Italy, one in Spain and one in Switzerland. In total 67
cases were randomised and included in the baseline demo-
graphic data and in the assessment of tolerability. Of these, 57
cases received the full protocol correctly and were included in
the analysis of efficacy (Table 1).
Demographic characteristics and baseline data
The demographic characteristics of the 67 dogs are shown in
Table 2; there were no significant differences between the two
The frequencies of the separation-related behaviours
shown by the 57 dogs which adhered to the full protocol are
illustrated in Fig 1. The most common signs included:
destruction (72 per cent), barking (67 per cent), defaeca-
tion/urination (53 per cent), feeding problems (46 per cent),
excessive licking (40 per cent), lack of adaptation to change
(35 per cent), sleeping problems (23 per cent) and hyper-
salivation/vomiting (17·5 per cent); too few dogs showed this
last behavioural sign to allow statistical analysis. Most of the
signs were well balanced between the two groups except for
defaecation/urination and feeding problems; there were sig-
nificantly more dogs in the clomipramine treatment group
with defaecation/urination problems (P<0·05), and more
dogs in the
DAP group with feeding problems, but the differ-
ence did not reach significance. In the clomipramine treat-
ment group the problem had been present, on average, for
1·7 years (range one month to eight years), and in the
group for 1·5 years (range one month to six-and-a-half
Assessment of efficacy
The results of the global assessment by the owners of the main
parameters chosen to assess efficacy are shown in Table 3.
Equivalence testing for independent binary endpoints via the
Hauck-Anderson corrected classical procedure (Tu 1997)
fixed the lower range for the dogs which adhered to the pro-
tocol at –0·08 and for all the dogs at –0·13. These two results
are within the specified limit of –0·2, indicating that the
treatment was not inferior to the clomipramine treatment.
The results for each particular behavioural sign are shown in
Tables 4 and 5. There were no significant differences between
the two groups.
The results for the secondary distress signs (Table 5) were
also not significantly different between the two groups. Both
Papers & Articles
Variable Clomipramine DAP
Age (years)
Mean 2·81 2·82
Median 1·5 1·5
Range 0·65–9·0 0·55–13
Male 13 (42%) 20 (56%)
Neutered 3 1
Entire 10 19
Female 18 (58%) 16 (44%)
Neutered 6 4
Entire 12 12
Weight (kg)
Mean 17·5 17·3
Median 16 15·5
Range 5–35·5 4–39·1
Pure breed 20 (65%) 24 (67%)
Mixed breed 11 12
TABLE 2: Sex, breed and mean, median and ranges of the ages
and weights of the 31 dogs treated with clomipramine and the
36 dogs treated with dog-appeasing pheromone (
Sleeping problems
Excessive licking
Feeding problems
Lack of adaption
to change
FIG 1: Numbers and percentages of the 57 dogs treated for 28 days with either
clomipramine (CLO) or dog-appeasing pheromone (DAP) which showed particular
behavioural signs when they were separated from their owners. * Significant difference,
Effect on abnormal behaviour
Reduced +
Category No change (%) Reduced (%) Disappeared (%) disappeared (%) Total
Full protocol
CLO 8 (30) 13 (48) 6 (22) 19 (70) 27
DAP 5 (17) 20 (66) 5 (17) 25 (83) 30
All the dogs
CLO 10 (32) 15 (49) 6 (19) 21 (68) 31
DAP 9 (25) 22 (61) 5 (14) 27 (75) 36
CLO Clomipramine, DAP Dog-appeasing pheromone
TABLE 3: Global assessments of the effectiveness of the two treatments on the behaviour of
the 57 dogs which adhered to the full protocol and on the behaviour of all 67 dogs
Worse No Reduced Disappeared Reduced +
Treatment Behaviour (%) change (%) (%) (%) disappeared (%) Total
Destruction 0 5 (25) 8 (40) 7 (35) 15 (75) 20
urination 0 2 (12) 6 (29) 10 (56) 16 (89) 18
Vocalisation 2 (11) 2 (11) 9 (50) 5 (28) 14 (78) 18
Destruction 0 2 (9) 7 (32) 13 (63) 20 (91) 22
urination 0 3 (25) 5 (42) 4 (33) 9 (75) 12
Vocalisation 0 7 (35) 8 (40) 5 (25) 13 (65) 20
TABLE 4: Effects of treatment with clomipramine (CLO) or dog-appeasing pheromone (DAP)
for 28 days on the main separation-related disorders in the dogs on December 26, 2012 - Published by veterinaryrecord.bmj.comDownloaded from
The Veterinary Record, April 23, 2005
treatments greatly reduced sleeping problems and improved
the other signs by more than 50 per cent.
Two dogs in each treatment group were withdrawn
before day 28 owing to a lack of efficacy. In the clomipr-
amine treatment group one dog was withdrawn before day
14 because its diarrhoea did not decrease, and the other was
withdrawn after day 14 because it ate part of the electricity
supply and set the house on fire; the owners of both these
dogs requested that they be euthanased. In the
DAP group
one dog was withdrawn before day 14 because its owner
complained of systematic vomiting after the administration
of the placebo pills; the second dog was withdrawn after day
14 because the owner’s neighbour lodged a complaint
against him because the dog vocalised too much and the
treatment had not reduced the problem. The owner gave the
dog to a member of his family because its problems of
destruction and urination were rated as disappeared’ and
‘reduced’ respectively.
Assessment of tolerability
The frequencies of reported undesirable behaviours are
shown in Table 6, regardless of their severity or the duration
of the treatment. Significantly more of the dogs in the
clomipramine treatment group showed undesirable behav-
iours (P<0·005); gastrointestinal problems affected seven
dogs, changes in appetite affected six and two dogs were
lethargic. In the
DAP group no particular undesirable behav-
iour was more common than the others. Four of the dogs in
the clomipramine treatment group and one in the
DAP group
had many episodes of vomiting immediately after the treat-
ment was administered; they may have been related to the
method of administration rather than to the treatment itself.
When these cases were excluded from the analysis, there were
still significantly more of the dogs in the clomipramine treat-
ment group which showed undesirable behaviours (P<0·05).
One dog in the
DAP group showed aggressive behaviour
at the end of the trial although it had had no previous his-
tory of aggressive behaviour. Complementary questioning
revealed the appearance of typical signs of dominance and
territorial aggression; all these signs disappeared after two
weeks of a behavioural plan for dominance aggression. One
dog in the
group showed signs of discomfort and fear
micturition at the beginning of the treatment every time the
owner returned home. At visit 2 (phone contact) it appeared
to the vet that the behavioural plan was being applied too
enthusiastically. After further explanation of some points of
the protocol, the owner changed his attitude towards his dog
and the signs disappeared from day 15 to the end of the treat-
Assessment of compliance
Only 18 of the owners of the dogs on the clomipramine
treatment adhered to the protocol perfectly, but in the other
cases the compliance was better than 80 per cent. In the
group two owners maintained the treatment for less than 50
per cent of the prescribed time, but the others maintained it
for more than 80 per cent of the time. In more than 97 per
cent of the cases the weight of the solution vaporised was
equal to the theoretical value.
The results of this trial indicate that
DAP, in combination with
a behavioural plan, can quickly reduce the undesirable behav-
iours exhibited by dogs suffering from separation-related
problems and overattachment. There was a marked decrease
in the main behavioural signs of destruction, vocalisation and
urination/defaecation, and also in the secondary distress signs
of excessive licking, sleeping and feeding problems, and
gastrointestinal disorders. The results produced by
DAP were
similar to those produced by the reference treatment,
clomipramine, but although its efficacy appeared to be the
same, the treatment with
DAP had practical benefits: unde-
sirable effects were reported less frequently and the simple
form of administration potentially increased the compliance
to the overall protocol.
The statistical methods used made it possible to draw the
conclusion that the
DAP treatment was not inferior to
clomipramine, rather than that the two treatments were not
significantly different in efficacy, a conclusion which is less
open to misinterpretation (Com-Nougue and Rodary 1987,
Garbe and others 1993, Bristol 1999, Steinijans and others
2000, Chrisley and Reid 2003). However, three methodolog-
ical aspects had to be observed in order to use this approach.
First, the design features which applied to the previous study
of the reference molecule were adopted in order to make up
for the lack of internal validity; secondly, the behavioural
acceptance range followed the guidelines (
US Food and Drug
Administration 1992, Anon 1999) and corresponded to the
arbitrary margin proposed in the literature (Com-Nougue
and Rodary 1987); thirdly, the data from both the dogs which
met the conditions of the protocol in full, and all the dogs,
were analysed.
The demographic data show that the groups treated with
and clomipramine were not significantly different in
terms of the distributions of dogs of different sex, age and
Papers & Articles
Hypersalivating/ Lack of adaptation
Sleeping problem (%) Self-licking (%) Feeding problem (%) vomiting (%) to change (%)
Treatment Day 0 Day 28 Day 0 Day 28 Day 0 Day 28 Day 0 Day 28 Day 0 Day 28
CLO 6 0 10 5 (50) 9 4 (44) 6 1 (17) 11 4 (36)
DAP 5 2 (29) 13 5 (38) 7 9 (53) 4 2 (50) 9 3 (33)
TABLE 5: Results of treatment with clomipramine (CLO) or dog-appeasing pheromone (DAP) for 28 days on the dogs which showed
secondary signs of separation-related disorders
Undesirable behaviour
Gastrointestinal signs/appetite
Intermittent vomiting/gastritis 1 1
Vomiting just after administration 4 1
Intermittent diarrhoea/colitis 2 0
Anorexia/weight loss 3 1
Increased appetite/weight gain 3 1
Constipation 1 0
Hypersalivation 1 1
Neurological signs
Lethargy/sleepiness 2 1
Trembling/discomfort 0 1
Aggression 0 1
Hyperactivity crisis 2 0
Other medical conditions
Fear micturition 0 1
Total 19 9*
* Significant difference (P<0·05)
TABLE 6: Numbers of dogs which showed undesirable
behaviours while being treated for 28 days with clomipramine
CLO) or dog-appeasing pheromone (DAP) on December 26, 2012 - Published by veterinaryrecord.bmj.comDownloaded from
The Veterinary Record, April 23, 2005
breed. The demographic data were also similar to those of the
dogs in the reference study, except for sex. In the reference
study two-thirds of the dogs were male, whereas in this study
only half of the dogs were male, but the difference was not sig-
nificant (King and others 2000). In the reference trial the per-
centage of neutered dogs of both sexes was significantly
greater. Data from a previous study (Gaultier 2001) suggest
that this difference is probably linked to local habits and not
to a selection bias: dogs are less likely to be neutered in the
countries of central and southern Europe than in northern
Europe and North America.
The inclusion criteria were strict, particularly the require-
ment that the dog initially showed signs of hyperattachment.
This criterion was applied for two reasons. First, because the
new trial was designed to have the same entry criteria as the
reference trials, and secondly, because recent data have shown
that there is a qualitative difference between dogs showing
separation-related problems and hyperattachment and those
showing separation-related problems but not hyperattach-
ment (Gaultier 2001), as had been suggested by some authors
in the field of pet behaviour (Voith and Borchelt 1985,
McCrave 1991, Pageat 1995). Thus, it is important to recog-
nise that the dogs investigated were not representative of all
dogs with separation-related problems but only of dogs with
both separation-related problems and hyperattachment. The
fact that all the dogs showed signs of hyperattachment is
important because, according to King and others (2000), it
was probably one of the main reasons for the relative failure
to demonstrate a benefit of clomipramine in the trial in the
UK by Podberscek and others (1999).
The proportions of dogs behaving destructively, vocalis-
ing and house-soiling, were respectively 72, 67 and 53 per
cent, and similar to the proportions observed in the reference
study (73, 71 and 45 per cent) (King and others 2000) and to
data in the literature (Petit and others 1999, Gaultier 2001).
The proportions of dogs in which these behaviours were
‘reduced’ or disappeared’ by the clomipramine treatment in
this study were, respectively, 75, 89 and 78 per cent compared
with 81, 77 and 58 per cent in the reference trial. These
unwanted behaviours occurred in the same proportion in the
two treatment groups except for urination/defaecation,
which, at the beginning of the trial, affected a much higher
proportion of the dogs to be treated with clomipramine. As
a result, care is required in evaluating the results of the trial
for this behaviour. The results indicated that the
clomipramine treatment was more effective than
although the difference was not statistically significant. This
result might be expected on the basis of the drug’s pharma-
cological action; it should decrease defaecation and urination
by the combined effect of its peripheral anti-cholinergic
action (Balant-Gorgia and others 1980, Benfield and others
1991) and its central anxiolytic action. Vocalisation was the
behaviour that the two protocols were least effective in reduc-
The results indicate that both treatments were effective in
reducing secondary signs of distress. Clomipramine appeared
to be excellent for treating sleeping problems and hypersali-
vation/vomiting; this last result could have been expected on
the basis of the drug’s peripheral anti-cholinergic action and
its 5-hydroxy tryptamine reuptake inhibitor action. The
results obtained with
DAP were also good, with between 50 to
70 per cent success, but it appeared to be less effective than
clomipramine. However, the small number of cases prevented
any statistical analysis and any definitive conclusion in com-
paring the two treatments. Both treatments were successful in
nearly half the dogs with feeding problems, but the initial dif-
ference between the proportions of dogs with these problems
made it impossible to draw any firm conclusion. In previous
trials clomipramine had shown evidence of being effective for
treating canine acral lick dermatitis (Goldberger and
Rapoport 1991, Mertens and Dodman 1996), and the rapid
and substantial decrease in self-licking observed in the dogs
treated with clomipramine provided further evidence of its
value; the
DAP treatment gave similar results, with potentially
more cases rated as a success. Both products induced great
improvements in the dogs’ability to adapt to variations in the
environment, indicating that
DAP should be useful in situa-
tions inducing fear. This result is consistent with a previous
study of the effect of
DAP on the behaviour of dogs fearful of
fireworks (Sheppard and Mills 2003).
This is the first controlled study of the use of
DAP together
with a behavioural plan in the treatment of dogs with sepa-
ration-related problems and hyperattachment. The results
showed that it reduced many of the problem behaviours.
Furthermore, the pheromone did not appear to induce the
commonly reported undesirable side effects inherent in the
use of drugs, and its convenient form of administration
increases the likelihood of owners’ compliance.
This study was made possible by the help of the following
investigators: Dr Raimondo Colangeli (Italy), Dr Victoria Coll
(Spain), Dr Jacques Cordel (France), Dr Christian Diaz
(France), Dr Alain Gosse (France), Dr Thierry Habran
(France), Dr Jean-Luc Halbout (France), Dr Catherine Mège
(France), Dr Gérard Muller (France), Dr Jean-François Ravier
(France), Dr Gérard Roussignol (France) and Dr Anne-Marie
Villars (Switzerland).
ANON (1999) ICH Harmonised Tripartite Guideline: Statistical principles for
clinical trials. Statistics in Medicine 18, 1905-1942
APPLEBY, D. & PLUIJMAKERS, J.(2003) Separation anxiety in dogs: the func-
tion of homeostasis in its development and treatment. Veterinary Clinics of
North America: Small Animal Practice 33, 321-344
BALANT-GORGIA, A. E., GEX-FABRY, M. & BALANT, L. P. (1980) Clinical
pharmacokinetics of clomipramine. Clinical Pharmacokinetics 20, 447-462
BENFIELD, D. P., HARRIES, C. M. & LUSKOMBE, D. K. (1991) The pharma-
cological aspects of desmethylclomipramine. Postgraduate Medicine and
Pharmacology 56, 13-18
BLACKWELL, E. J., CASEY, R. A. & BRADSHAW, J. W. S. (2002) The efficacy
of behaviour modification therapy in the treatment of separation-related
behaviour problems in dogs. In Proceedings of the 8th
ESVCE Meeting on
Veterinary Behavioural Medicine. Eds J. Dehasse, E. Biosca. Granada, Spain,
October 2, 2002. pp 195-199
BORCHELT, P. L. & VOITH, V. L. (1982) Diagnosis and treatment of separa-
tion-related behaviour problems in dogs. Veterinary Clinics of North America:
Small Animal Practice 12, 625-635
BRISTOL, D. R. (1999) Clinical equivalence. Journal of Biopharmaceutical
Statistics 9, 549-561
CHRISLEY, M. C. & REIDS, S.W. J. (2003) No significant difference: use of sta-
tistical methods for testing equivalence in clinical veterinary literature.
Journal of the American Veterinary Medical Association 222, 433-437
COM-NOUGUE, C. & RODARY, C. 1987) Revue des procédures statistiques
pour mettre en évidence l’équivalence de deux traitements. Revue Épidémi-
ologique et Santé Publique 35, 416-430
FLANNIGAN, G.& DODMAN, N. H. (2001) Risk factors and behaviours asso-
ciated with separation anxiety in dogs. Journal of the American Veterinary
Medical Association 219, 460-466
GARBE, E., RÖHMEL, J. & GUNDERT-REMY, U. (1993) Clinical and statis-
tical issues in therapeutic equivalence trials. European Journal of Clinical
Pharmacology 45, 1-7
GAULTIER, E. (2001) Separation-related behaviour problems: diagnostic cri-
teria identification using a cluster analysis. In Proceedings of the Third World
Meeting on Ethology. Eds K. E. Overall, D. S. Mills, S. E. Heath, D. Horwitz.
Vancouver, Canada, August 7 to 8, 2001. pp 76-82
GOLDBERGER, E. & RAPOPORT, J. L. (1991) Canine acral lick dermatitis:
response to the antiobsessional drug clomipramine. Journal of the American
Animal Hospital Association 27, 179-182
HEATH, S. (2002) Dealing with separation problems in dogs. In Scientific
Proceedings of the 45th Annual Congress of the British Small Animal
Papers & Articles on December 26, 2012 - Published by veterinaryrecord.bmj.comDownloaded from
The Veterinary Record, April 23, 2005
Papers & Articles
Veterinary Association. Birmingham, UK, April 4 to 7, 2002. pp 536-538
JAGOE, A. & SERPELL, J. (1995) Owner characteristics and interations and the
prevalence of canine behaviour problems. Applied Animal Behaviour Science
47, 31-42
THE CLOCSA GROUP (2000) Treatment of separation anxiety in dogs with
clomipramine: results from a prospective, randomized, double-blind,
placebo-controlled,parallel-group, multicenter clinical trial. Applied Animal
Behaviour Science 67, 255-275
LANDSBERG, G. M. (1991) The distribution of canine behavior cases at three
behavior referral practices. Symposium of behavior problems in pets.
Veterinary Medicine 86, 1011-1018
LESAINE, C. (1996) L’abandon et l’adoption du chien. Thèse de doctorat en
Médecine Vétérinaire. Ecole Vétérinaire de Nantes. pp 54-90
& BAILEY, J. P. (1995) Factors predisposing dogs to separation problems. In
Proceedings of the 29th International Congress of the International Society
for Applied Ethology. Eds S.M. Rutter, J. Rushen, H. D. Randle, J. C. Eddison.
UK, August 1995. pp 103-104
MCCRAVE, A. E. (1991) Diagnostic criteria for separation anxiety in the dog.
Advances in Companion Animal Behavior. Veterinary Clinics of North
America: Small Animal Practice 21, 247-255
MERTENS, P. & DODMAN, N. H. (1996) Medikamentöse Behandlung der
akralen Leckdermatitis des Hundes. Kleintierpraxis 41, 327-337
O’FARRELL, V. (1997) Owner attitudes and dog behaviour problems. Applied
Animal Behaviour Science 52, 205-213
OVERALL,K. L.(1997) Fears, anxieties and stereotypies. In Clinical Behavioral
Medicine for Small Animals. St Louis,
CV Mosby. pp 209-250
& FRANK, D. (1999) Qualitative and quantitative differences in vocalizations
by dogs affected with separation anxiety and unaffected dogs using sono-
graphic analysis. In Proceedings of the Second World Meeting on Ethology.
Lyon, France, September 21 to 22, 1999. pp 108-113
PAGEAT, P. (1995) Nosographie des troubles comportementaux du chien. In
Pathologie due Comportement du Chien. 1st edn. Paris, Editions du Point
Vétérinaire. pp 274-281
PAGEAT, P. (2000) Pig appeasing pheromone to decrease stress, anxiety and
aggressiveness. United States Patent number 6,077,867
PAGEAT, P. & GAULTIER, E. (2003) Current research in canine and feline
pheromone. Update in Clinical Veterinary Behavior. Veterinary Clinics of
North America: Small Animal Practice 33, 1-25
J. (1999) Efficacy of clomipramine in the treatment of separation anxiety in
dogs: clinical trial. Revue de Médecine Vétérinaire 150, 133-140
PODBERSCEK, A. L., HSU, Y. & SERPELL, J. A. (1999) Evaluation of clomipr-
amine as an adjunct to behavioural therapy in the treatment of separation-
related problems in dogs. Veterinary Record 145, 365-369
SHEPPARD, G. & MILLS, D. S. (2003) Evaluation of dog appeasing pheromone
as a potential treatment for fear of fireworks by dogs. Veterinary Record 152,
SIMPSON, B. S. (2000) Canine separation anxiety. Compendium on Continuing
Education for the Practicing Veterinarian 22, 328-339
STEINIJANS, V. W., NEUHÄUSER, M. & BRETZ, F. (2000) Equivalence con-
cepts in clinical trials. European Journal of Drug Metabolism and
Pharmacokinetics 25, 38-40
TAKEUCHI, Y. HOUPT, K. H. & SCARLETT, J. N. (2000) Evaluation of treat-
ments for separation anxiety in dogs. Journal of the American Veterinary
Medical Association 217, 342-345
TU, D. (1997) A comparative study of some statistical procedures in establish-
ing therapeutic equivalence of nonsystemic drugs with binary endpoints.
Drug Information Journal 51, 1291-1300
TUBER, D. S., HOTERSALL, D.& PETERS, M. F. (1982) Treatment of fears and
phobias in dogs. Veterinary Clinics of North America: Small Animal Practice
12, 607-624
US FOOD AND DRUG ADMINISTRATION (1996) Division of Anti-Infective
Drug Products. Points to consider. Clinical development and labelling of
anti-infective drug products. March 1995 addendum.
guidance/hpptc.htm. Accessed April 7, 2005
VAN DER BORG, J. A. M., NETTO, W. J. & PLANTA, D. J. U. (1991)
Behavioural testing of dogs in animal shelters to predict problem behaviour.
Applied Animal Behaviour Science 32, 237-251
VOITH, V. L. & BORCHELT, P. L. (1985) Separation anxiety in dogs.
Compendium on Continuing Education for the Practicing Veterinarian 7, 42-52
WRIGHT, J. C. & NESSELROTE, M. S. (1987) Classification of behavior prob-
lems in dogs: Distribution by age, breed,sex, and reproductive status. Applied
Animal Behaviour Science 19, 169-178 on December 26, 2012 - Published by veterinaryrecord.bmj.comDownloaded from
doi: 10.1136/vr.156.17.533
2005 156: 533-538Veterinary Record
E. Gaultier, L. Bonnafous, L. Bougrat, et al.
separation-related disorders in dogs
clomipramine for the treatment of
dog-appeasing pheromone with
Comparison of the efficacy of a synthetic
Updated information and services can be found at:
These include:
Article cited in:
Email alerting
the box at the top right corner of the online article.
Receive free email alerts when new articles cite this article. Sign up in
To request permissions go to:
To order reprints go to:
To subscribe to BMJ go to: on December 26, 2012 - Published by veterinaryrecord.bmj.comDownloaded from
... UBs have a variety of aetiologies, including stress-coping mechanisms, responses to somatic conditions (e.g., polyuria relates to polydipsia with multiple potential causes), and behavioural pathologies such as abnormal repetitive behaviours [17,18]. Many UBs, such as SRB, indicate compromised welfare and therefore changing the negative emotional states that underlie these behaviours is a clear priority [19]. Meanwhile, the consequences of UBs can be profound for both dogs and owners [20] especially for behaviours that commonly lead to relinquishment and euthanasia [21]. ...
... Many contributing factors are reported to influence decision-making on the use of psychopharmaceutical therapy for UBs. They include perceptions by veterinary teams and dog owners of what is 'normal' and acceptable canine behaviour as well as issues around cost and safety [32] and the ease of administration [19], which have been reviewed elsewhere (e.g. [33]). ...
... The estimated one-year period prevalence for dogs with at least one drug-prescribed UB was 0.4%. Given that previous studies have estimated that over 95% of dogs are perceived by their owners as performing UBs [5,6], the current results suggest that only a small proportion of [19], reluctance to admit the UB is an issue or lack of awareness of psychopharmaceutical treatment possibilities for UBs. Other practical barriers may include owners finding regular oral administration of drugs more difficult than behaviour modifying products in diffuser or spray formats, e.g. ...
Full-text available
Undesirable behaviours (UBs) in dogs are common and important issues with serious potential welfare consequences for both the dogs and their owners. This study aimed to investigate the usage of drug therapy for UBs in dogs and assess demographic risk factors for drug-prescribed UBs within the dog population under primary-care veterinary care in the UK in 2013. Dogs receiving drug therapy for UB were identified through the retrospective analysis of anonymised electronic patient records in VetCompass™. Risk factor analysis used multivariable logistic regression modelling. The study population comprised 103,597 dogs under veterinary care in the UK during 2013. There were 413 drug-prescribed UBs recorded among 404 dogs. The prevalence of dogs with at least one UB event treated with a drug in 2013 was 0.4%. Multivariable modelling identified 3 breeds with increased odds of drug-prescribed UB compared with crossbred dogs: Toy Poodle (OR 2.75), Tibetan Terrier (OR 2.68) and Shih-tzu (OR 1.95). Increasing age was associated with increased odds of drug-prescribed UB, with dogs ≥ 12 years showing 3.1 times the odds compared with dogs < 3 years. Neutered males (OR 1.82) and entire males (OR 1.50) had increased odds compared with entire females. The relatively low prevalence of dogs with at least one UB event that was treated with a drug in 2013 could suggest that opportunities for useful psychopharmaceutical intervention in UBs may be being missed in first opinion veterinary practice. While bodyweight was not a significant factor, the 3 individual breeds at higher odds of an UB treated with a behaviour modifying drug all have a relatively low average bodyweight. The current results also support previous research of a male predisposition to UBs and it is possible that this higher risk resulted in the increased likelihood of being prescribed a behaviour modifying drug, regardless of neuter status.
... Dog appeasing pheromone is a synthetic analog of a pheromone secreted by the intermammary sebaceous glands of the bitch after parturition and has a relaxing effect on puppies [4]. This analog has been extensively studied and has been shown to help reduce signs of stress in different stressful situations even in adult dogs [5][6][7][8][9][10][11][12][13][14][15]. It is available in a range of products including collars and electric diffusers and is used to help relax dogs during stressful events. ...
... In the second study, we tested the efficacy of the new long-lasting diffusing gel against the reference plug-in product that had shown effectiveness in other studies [11,[14][15][16][17][18]. To assess the effectiveness of the devices on behavior and stress at home, two different scales were used by owners: one to assess the general behavior and sources of fear of the dogs, based on 13 behaviors commonly observed by owners and identified in previous studies [19][20][21] and another one assessing specific signs of stress that owners could observe and based on 11 signs, using the commonly used approach of a visual-analog scale [22]. ...
... The reference collar and diffuser have shown effectiveness in different stressful situations, including during separation from the owner [14], loud noises [8], car travel [5], and when introducing a puppy to its new home [13]. Most studies involved the evaluation of specific criteria by a specialized veterinarian. ...
Full-text available
Devices that release a synthetic analog of the canine-appeasing pheromone can help to relax dogs during stressful situations, but they usually last for only one month. Two new devices with this analog were tested by owners of dogs showing signs of stress in a range of everyday situations: Zenidog™ collar, lasting three months, and Zenidog™ diffusing gel, lasting two months (Virbac, Carros, France). They were compared against reference products that last for one month. In the three-month study with collars, one group received Zenidog™ collar, one received the reference collar, and one group of dogs wore an antiparasitic collar alongside a Zenidog™ collar. In the two-month study with diffusers, groups received either the unpowered Zenidog™ gel diffuser or the reference electric diffuser. Owners regularly completed a questionnaire that assessed seventeen general behaviors and sources of fear and eleven specific signs of stress. Global scores for these two main scales were calculated, and the evolution of scores was compared between groups. Non-parametric tests with a Bonferroni correction were used for statistical analysis. An improvement of all global scores was observed in all groups (p < 0.001), including in puppies, and there was no difference between groups. Zenidog™ devices were as effective as the reference devices and lasted longer.
... For severe cases of separation anxiety, strict desensitization and counter-conditioning protocols, aimed at altering the dog's emotional reaction to the owner's departure, have been demonstrated to be effective in improving behavior [6]. In addition, numerous studies have examined the efficacy of different anti-anxiety medications such as clomipramine [7,8] and fluoxetine [9,10], or more "natural" remedies such as dog-appeasing pheromone [7], which can be used in combination with the behavior modification protocols to assist in increasing the latter's efficacy. Numerous studies have been conducted assessing the efficacy of these treatment plans with varying degrees of success [11]. ...
... For severe cases of separation anxiety, strict desensitization and counter-conditioning protocols, aimed at altering the dog's emotional reaction to the owner's departure, have been demonstrated to be effective in improving behavior [6]. In addition, numerous studies have examined the efficacy of different anti-anxiety medications such as clomipramine [7,8] and fluoxetine [9,10], or more "natural" remedies such as dog-appeasing pheromone [7], which can be used in combination with the behavior modification protocols to assist in increasing the latter's efficacy. Numerous studies have been conducted assessing the efficacy of these treatment plans with varying degrees of success [11]. ...
Full-text available
Simple Summary Dogs are a social species and may experience negative emotions when left alone even for short periods of time. This study explored the effectiveness of different food-based enrichments on engaging dogs, and alleviating potential negative emotional states caused by social isolation. The results indicated that dogs spent the most time interacting with a long-lasting chew. They also responded to this enrichment with the most positive and calm emotions when compared to a treat-dispensing toy and a smart treat-dispensing device. Long-lasting chews should be further explored as an enrichment for improving dog emotional wellbeing during periods of separation from their caregivers. Abstract Dogs may experience negative emotional states when isolated from human caregivers and conspecifics. This study aimed to evaluate how dogs interact with different enrichments during a short period of social isolation, as a first step towards identifying methods for improving their emotional wellbeing. Using a cross-over design, dogs (n = 20) at the Waltham Petcare Science Institute were exposed to four different food-based enrichments while left alone in a familiar room for 20 min: long-lasting chew (Chew), kibble in a treat-dispensing toy (Toy), and kibble dispensed through a smart treat-dispensing device with (Device + Voice) and without (Device) a person talking to the dog. Time spent engaging with each enrichment item and emotional valence and arousal (7-point scale collected every 5-min) were scored from videos. The results of linear mixed models indicated Chew was the most successful enrichment, with dogs having lower arousal scores (p < 0.05 vs. Device and Toy) during the first five minutes of isolation, higher positive valence scores (p < 0.05 vs. all) during the second five minutes of isolation, and spending the most total time engaged (p < 0.01 vs. all). Based on these findings, long-lasting chews should be further explored to assess their impact on dog emotional wellbeing.
... The commercially-available dog appeasing pheromone (ADAPTIL ® , previously DAP; Ceva Sante Animale, Libourne, France) has been reported to reduce behaviours associated with fear and anxiety in puppies entering new environments [200] and in adult dogs during transport, veterinary settings, thunderstorms, and rescue shelters [173,194,[201][202][203]. Treatment with ADAPTIL ® has been found to be as effective as pharmaceutical treatments for the reduction in stress-related behaviours that occur as a result of separation anxiety [204]. This pheromone can be administered as an imbibed collar, diffuser, or aerolite spray. ...
... While it is possible to infer emotional states from indirect measures, such as behaviour, any given state can be expressed by a variety of behaviours [194]. Additionally, much of the literature on the use of ADAPTIL ® lacks baseline measures for individual animals (with some work relying entirely on owner surveys) or lack a blinded experimental design that would mitigate the introduction of observer bias [201,204]. ...
Full-text available
Thirty-six species of canid exist globally, two are classified as critically endangered, three as endangered, and five as near threatened. Human expansion and the coinciding habitat fragmentation necessitate conservation interventions to mitigate concurrent population deterioration. The current conservation management of wild canids includes animal translocation and artificial pack formation. These actions often cause chronic stress, leading to increased aggression and the suppression of the immune and reproductive systems. Castration and pharmaceutical treatments are currently used to reduce stress and aggression in domestic and captive canids. The undesirable side effects make such treatments inadvisable during conservation management of wild canids. Pheromones are naturally occurring chemical messages that modulate behaviour between conspecifics; as such, they offer a natural alternative for behaviour modification. Animals are able to distinguish between pheromones of closely related species through small compositional differences but are more likely to have greater responses to pheromones from individuals of the same species. Appeasing pheromones have been found to reduce stress- and aggression-related behaviours in domestic species, including dogs. Preliminary evidence suggests that dog appeasing pheromones (DAP) may be effective in wild canids. However, the identification and testing of species-specific derivatives could produce more pronounced and beneficial behavioural and physiological changes in target species. In turn, this could provide a valuable tool to improve the conservation management of many endangered wild canids.
... ADAPTIL ® is intended to reproduce the natural dog-appeasing pheromone released by the bitch from the mammary zone after whelping [18]. ADAPTIL ® is clinically proven to help dogs feel calm and relaxed in stressful situations [19][20][21][22][23][24][25][26][27]. It provides a strong signal of comfort and security to the puppies but, also, has the same effect on dogs of all ages. ...
... The selection of the bitches was independent of parity, but only mesocephalic or dolichocephalic breeds (based on the calculated cephalic index [29]) were selected. The groups of bitches were classified as small (<15 Kg), medium (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) and large (>25 Kg) [30]. In addition, each selected bitch was required to have a litter of at least three healthy puppies at 21 days postpartum to allow a minimum level of interactions between puppies. ...
Full-text available
ADAPTIL®, a dog-appeasing pheromone, was shown to modify the dam–puppies’ interactions during the neonatal period but could also influence the weaning period. Fourteen bitch/litter dyads continuously exposed to ADAPTIL® from the third/fourth weeks until the seventh/eighth weeks postpartum were compared to 11 dyads exposed to a placebo. Maternal and puppy behaviours were video-recorded, and at three time points (weeks three/four, weeks five/six and weeks seven/eight) after parturition. The well-being of the puppies and the overall relationship with the bitch were assessed using visual analogue scales (VAS) completed by the caregivers. All mothering behaviours, such as time of contact, licking and the amount of time dedicated to nursing puppies, decreased gradually from weeks three/four to weeks seven/eight. A switch in nursing position was observed over time: the use of the standing position increased compared to the lying position. The treatment had an effect on the nursing position: bitches in the ADAPTIL® group nursed more often in a lying (p = 0.007) or sitting position (p = 0.037), whereas for the placebo group, they favoured the standing position (p = 0.011). Once the puppies became more demanding for suckling, the bitches started showing rejection signs or aggressive growling, with a peak at weeks seven/eight. The pheromone seemed to reduce the intensity of avoidance in bitches exposed to ADAPTIL® at all time points. The score of all events combined as a sign of frustration showed a difference over the full period (p = 0.003), with the placebo group having a significantly higher score. From the caregiver perspective (through the VAS), under ADAPTIL®, the bitches were calmer when puppies tried to suckle (p = 0.001), more tolerant towards pups (p = 0.025), showed a greater motherly attitude (p = 0.016), the puppies cried less when left alone (p < 0.001) and interactions amongst pups were more harmonious (p = 0.055). Under ADAPTIL®, the bitches were less annoyed by the puppies, who seemed to cope better with frustration. The breeders perceived a benefit of the pheromone during the weaning period.
... The signs of separation anxiety such as destruction, defecation and urination were decreased, but the differences between the standard dose and the placebo groups in vocalization is not significant. Mild and transient vomiting was reported as a side effect in a small number of dogs [15]. ...
Separation anxiety is one of the most common canine-related disorders in dogs (Canis Familiaris) and charactered by the presentation of unacceptable levels of anxiety related behaviors in the absence of the human companion. While pharmaceutical treatment with antidepressant drugs shows some evidence for effectiveness, the impact is limited, and negative side effects are reported. In contrast, behavioral modification is proposed as an effective and safe method to address separation anxiety, but clinical research is lacking. This work reports the application of associative theory to animal behavioral treatment that considers the role of three senses for a treatment plan; vision, audition, and olfaction and has accumulated 129 successful cases in ten years. Summary data demonstrates the practical advantages including safety for the dogs and perceived effectiveness for the owners.
... A synthetic analogue of pig appeasing pheromone is available on the market and is commonly used by farmers in the pig industry [44]. The application of appeasing pheromones as pheromonotherapy simplifies treatment for anxiety and phobia-related issues in various species, such as dogs, cats [45][46][47], rabbits [43,48], and horses [49,50], reduces aggression among cats [51] and among dogs [52], and increases the welfare and performance of dairy cattle [53,54], beef cattle [55][56][57], and chicks [58], among others. ...
Full-text available
Background The practice of mixing unfamiliar pigs on farms is common but results in fighting, welfare problems and performance issues. Pigs have different ways of resolving social conflicts, including aggressive and affiliative behaviours. Synthetic appeasing pheromones have demonstrated many positive effects in animal husbandry and are regularly used by breeders to improve animal welfare and performance. The aim of the study was to investigate the effect of a new method of applying pig appeasing-pheromone (PAP) to the withers in an experimental model of pig mixing to determine whether PAP reduced aggression and fighting, increased prosocial behaviours, and improved behavioural and physiological indicators of welfare. Results PAP reduced fighting between mini-pigs (df = 1; F = 13.47; P = 0.001; mixed logistic regression). Even if not significant, agonistic behaviours tended to be reduced when the treatment was applied (df = 1; F = 4.14; P = 0.058; mixed logistic regression). Likewise, mini-pigs seemed to be scored as not aggressive at all (df = 1; F = 3.61; P = 0.070; GLMM) and to be less aggressive toward the other pig than when placebo was applied. Concerning the latency of the first contact without aggression, a significant effect was found between the PAP and placebo groups (df = 1; χ ² = 4.74; P = 0.0295; Cox model). Moreover, even if not significant, the treated mini-pigs seemed to spent more time looking at each other (df = 1; F = 3.59; P = 0.071; GLMM) and immobile and/or ground sniffing (df = 1; F = 3.18; P = 0.088; GLMM) than those that received placebo. No significant difference was found between groups for salivary cortisol concentration (df = 1; F = 0.10; P = 0.752; GLMM), but variances between groups were heterogeneous at every time. No significant difference was found between groups regarding alpha-amylase activity (df = 1; F = 0.25; P = 0.621; GLMM), but variances between groups were heterogeneous at T0, T1 and T3. These results indicate that the variability (dispersion) within each group was lower when PAP was applied than when the placebo was applied. Conclusions The new method of applying PAP improved welfare of mini-pigs (as models of domestic pigs) by reducing fighting, among other interesting results. PAP seems thus a promising biomimetic tool to enhance animal welfare in pig production systems.
... The expression of such problematic behaviors can be associated with specific interactions between the dog and keeper, as an excessive attachment of a dog with his/her keeper can change their behaviors in an undesirable way (Guy et al., 2001;Jagoe & Serpell, 1996;Storengen, Boge, Strom, Loberg, & Lingaas, 2014). Some studies indicate that hyper-attachment of dogs to their keepers (indicated by some dogs following their keeper from room to room and sleeping close to their keeper) is a clear sign of separation anxiety disorder (Gaultier, Bonnafous, Bougrat, Lafont, & Pageat, 2005;Storengen et al., 2014). ...
This study was used to evaluate whether the proximity of dogs to their human companions during sleep is associated with common problematic behaviors in canines, such as destroying objects, vocalizing excessively, urinating/defecating in inappropriate places (all when dogs are alone at home), and aggressive threats (growling or barking) and acts (biting) toward people. Over 60,000 dog keepers answered an online questionnaire that addressed where their dogs slept at night and the frequency with which they exhibited such behaviors. Except urinating/defecating in inappropriate places and biting people, other problematic behaviors were less frequent in dogs who slept inside the house. We conclude that dogs sleeping indoors (that is, closer to their keepers) less frequently exhibit aggressive threats and problematic behaviors that are commonly associated with separation anxiety.
Full-text available
Many dogs experience stress when separated from their caregivers, as well as when traveling in vehicles. Pet owners employ various approaches to managing these issues, from training, to giving medications and supplements, often with mixed results. Cannabidiol (CBD) can alleviate stress and anxiety in humans but the effect it has on canine stress is less well-documented. The present study aimed to understand the impact of being left alone and traveling in a car on measures of canine stress, and establish whether a single dose of a tetrahydrocannabinol (THC)-free CBD distillate could positively influence any measures of stress. In a blinded, parallel design study, a population of dogs were either left alone in a familiar room (n = 21) or underwent a short car journey (n = 19). A range of physiological and behavioral measures were collected pre, during and post-test. Significant changes in several stress-related measures (serum cortisol, mean ear temperature, heart rate, heart rate variability, whining and a stressed/anxious behavioral factor) were observed from baseline to test, with the car journey test paradigm eliciting a more pronounced stress response overall. The mitigating effect of CBD treatment varied by measure and test, with some indicating a significant reduction in canine stress compared to the placebo group. Additional research is required to fully understand the complex effect of CBD on canine wellbeing.
Olfactory signals play an essential role in communication in animals. Pheromones are volatile or nonvolatile chemicals that trigger social responses among animals. Therefore, pheromone treatment could, in theory, be used to modify horse behavior to improve human–horse relationships. Androstenone (5α-androst-16-en-3-one) is a steroidal pheromone found in the saliva of boars and elicits responses across species. However, its role in horse behaviors is not elucidated. This study investigated the effect of androstenone on horse behavior. Trainability (lowering head and moving hindfeet) and calmness tests (standing still with or without a stimulator) were performed with or without applying androstenone diluted with jojoba oil. Treatment with 10 μg/mL of androstenone applied 30 min before the tests significantly decreased the time for the horses to lower their head compared with the control. The results of the calmness tests had no significant differences compared with the control group. In the pressure mediation test for trainability assessment, a group of horses treated with 10 μg/mL of androstenone moved their hind feet in a significantly shorter time (p < 0.05) than the control group. As a result, androstenone appears to induce horses to be more accepting of general management and training.
Full-text available
Despite the popular idea that dog owners are often responsible in some way for their animals' behaviour problems, the scientific evidence is scarce and contradictory. Some studies have failed to detect any links between the quality of the owner-dog relationship and the occurrence of behaviour problems, while others suggest that some behaviour problems may be associated with certain aspects of owner personality, attitudes and/or behaviour.Using retrospective data from a sample of 737 dogs, the present study investigated the association between the prevalence of different behaviour problems and various aspects of either owner behaviour or owner-dog interactions. A number of statistically significant associations were detected: (a) between obedience training and reduced prevalence of competitive aggression (P < 0.02), separation-related problems (P < 0.001), and escaping and roaming (P < 0.05); (b) between the timing of the dogs' meal times and the occurrence of territorial-type aggression (P < 0.01); (c) between sleeping close to the owner and increased prevalence of competitive aggression (P < 0.01) and separation-related problems (P < 0.01); (d) between first-time ownership and the prevalence of dominance-type aggression (P < 0.001), separation-related problems (P < 0.05), fear of loud noises (P < 0.001), and various manifestations of overexcitability (P < 0.001); (e) between owners' initial reasons for acquiring a dog and the prevalence of dominance-type (P < 0.001), competitive (P < 0.01) and territorial aggression (P < 0.01). The possible practical implications of these findings are discussed.
Traditionally, the bioequivalence of a generic drug with the innovator's product is assessed by comparing their pharmacokinetic profiles determined from the blood or plasma concentration-time curves. This method may only be applicable to formulations where blood drug or metabolite levels adequately characterize absorption and metabolism not to the nonsystematic drugs categorized by the lack of systemic presence. When pharmacologic effects of the drugs can be easily measured pharmacodynamic effect studies can be used to assess the therapeutic equivalence of nonsystemic drugs. When analytical methods or other tests cannot be developed to permit the use of the pharmacodynamic method, therapeutic equivalence clinical trials to compare one or several clinical endpoints may be the only suitable method of establishing therapeutic equivalence. This paper evaluates by Monte-Carlo simulations the fixed sample performances of some two one-sided tests procedures when the endpoints of the therapeutic equivalence trials are binary.
Treatment of canine acral lick dermatitis (ALD) represents a challenge for veterinarians. Our retrospective open label clinical study summarizes detailed follow up data on 10 cases of ALD treated with clomipramine (2 mg/kg, once daily, orally). Clomipramine therapy led to reduced self-licking and caused significant healing of ALD lesions in 8 of 10 cases. Aside from transident lethargy and polydipsia, no other side effects were reported. On the basis of these clinical experiences it appears that clomipramine is an effective treatment for true (psychogenic) ALD.
Separation anxiety is a clinical syndrome that can occur when dogs are estranged from owners or caregivers. It is characterized by behavioral and autonomic signs of anxiety, including destructiveness, housesoiling (urinary or fecal), distress vocalization, pacing or digging, hypersalivation, and self-trauma. Effective treatment focuses on environmental management, behavior modification techniques, and pharmacotherapy. Without proper treatment, the misbehavior can negatively affect the human-animal bond. Affected dogs are commonly relinquished to animal shelters, where they may be constantly placed in other homes or euthanized.
This clinical trial compares the efficacy and the tolerability of 4 dose rates of clomipramine - 0.25 to 0.5 mg/kg, 0.51 to 1 mg/kg, 1.1 to 2 mg/kg and 2.1 to 4 mg/kg administered twice a day - vs. a placebo in the treatment of separation anxiety. Behavioural therapy was given to all groups. Dogs weighing over 5 kg, of various breeds, age and sex were included. The efficacy was assessed after evaluation by the owner and the veterinarian at day 7, 14, 21, 28, and 60, based on the disturbances (destruction, urination, barking) caused by the dog, the relationship between the dog and the owner, and generalized anxiety symptoms. All these efficacy criteria clearly demonstrated that a daily dose of 2 to 4mg/kg (1-2mg/kg b.i.d) of clomipramine was the most effective dose : the cure rate was 70 % with clomipramine at this dose vs. 20 to 30 % in the other groups. Treatment was well tolerated at all doses of clomipramine.
Traditionally, the bioequivalence of a generic drug with the innovator's product is assessed by comparing their pharmacokinetic profiles determined from the blood or plasma concentration-time curves. This method may only be applicable to formulations where blood drug or metabolite levels adequately characterize absorption and metabolism, not to the nonsystematic drugs categorized by the lack of systemic presence. When pharmacologic effects of the drugs can be easily measured, pharmacodynamic effect studies can be used to assess the therapeutic equivalence of nonsystemic drugs. When analytical methods or other tests cannot be developed to permit the use of the pharmacodynamic method, therapeutic equivalence clinical trials to compare one or several clinical endpoints may be the only suitable method of establishing therapeutic equivalence. This paper evaluates by Monte-Carlo simulations the fixed sample performances of some two one-sided tests procedures when the endpoints of the therapeutic equivalence trials are binary.
Although separation anxiety is one of the most common problems encountered by the behavioral specialist, there is a lack of consensus about how it should be defined. Additionally, the interrelation between separation anxiety, fear, and phobia is complex and poorly understood. These factors have obvious implications for clear diagnosis and the selection of an appropriate treatment plan. This article discusses a mechanism that may reduce these conceptual and practical difficulties.