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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
2003).
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).
MATERIALS AND METHODS
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,
CD, DipECVBM
,
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.
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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
dogs.
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.
Treatments
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
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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
DAP
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
results.
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
significant.
RESULTS
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
groups.
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
DAP
group for 1·5 years (range one month to six-and-a-half
years).
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
DAP
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
Treatment
Variable Clomipramine DAP
Age (years)
Mean 2·81 2·82
Median 1·5 1·5
Range 0·65–9·0 0·55–13
Sex
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
Breed
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 (
DAP)
Number
25
20
15
10
5
0
70%
73%
67%
67%
40%
22%
23%
37%
43%
33%
57%
22%
13%
41%
30%
67%
Destruction
Vocalisation
Defaecation/
urination*
Sleeping problems
Excessive licking
Feeding problems
Hypersalivating/
vomiting
Lack of adaption
to change
■ CLO
■ DAP
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,
P<0·05
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
CLO
Destruction 0 5 (25) 8 (40) 7 (35) 15 (75) 20
Defaecation/
urination 0 2 (12) 6 (29) 10 (56) 16 (89) 18
Vocalisation 2 (11) 2 (11) 9 (50) 5 (28) 14 (78) 18
DAP
Destruction 0 2 (9) 7 (32) 13 (63) 20 (91) 22
Defaecation/
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
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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
DAP
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
DAP
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-
ment.
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
DAP
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.
DISCUSSION
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
DAP
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
Treatment
Undesirable behaviour
CLO DAP
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)
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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
DAP,
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-
ing.
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.
ACKNOWLEDGEMENTS
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).
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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
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