Comprehensive References

Transcription

1 Comprehensive References Sans titre /02/15 14:46 10:07

2 Foreword This review is designed to give general practitioners and other animal health professionals an accurate and simple overview of the clinical trial data* supporting the use of synthetic pheromone products Adaptil ** and Feliway. The summaries included in this publication have been written following consultation with the original authors and are in line with the latest developments in the field of pheromonatherapy. The review is also intended to be used in practice as a reference guide of efficacy data and recommendations for pheromones in dogs and cats. Ceva would like to thank the authors of each paper included in this review for their help in editing the copy and allowing us to publish summaries of their work. Special thanks also go to the contributing editors for their help in writing and editing this review: Jon Bowen BVetMed DipAS(CABC) MRCVS Professor Danielle Gunn-Moore BSc BVM&S PhD FHEA MACVSc MRCVS Sarah Heath BVSc DipECVBM-CA CCAB MRCVS Professor Daniel Mills BVSc PhD CBiol FIBiol FHEA CCAB DipECVBM-CA MRCVS Ceva Santé Animale * The original papers are available on request from Ceva Santé Animale. ** Please note that Adaptil is the new name for D.A.P. since mid of Consequently, all papers published until 2011 relate to the D.A.P. name.

3 Contents An introduction to pheromonatherapy by Sarah Heath What is Adaptil Adoption period Socialisation and training Kennels and rescue centres Separation-related behavioural problems Sound sensitivities Veterinary practice use Car travel What is Feliway Feline urine marking Travel and new environments Veterinary practice use Feline idiopathic cystitis Pheromonatherapy: Further r reading Ceva Contacts

4 Introduction to Pheromonatherapy by Sarah Heath BVSc DipECVBM-CA CCAB MRCVS Understanding pheromones Pheromones are substances that regulate behaviour by olfactory means. They are natural chemicals that play an important role in intraspecific communication. Pheromones can convey many different types of information. They may be used to communicate details of an individuals sexual cycle, social rank or arousal state, while also playing an important part in territorial marking and individual recognition. Those produced commercially are synthetic analogues of pheromones involved in regulating response to stress in the species concerned. Olfactory communication The perception of pheromones is largely accomplished by the vomeronasal (or Jacobson s) organ, which lies just above the hard palate near the inter-nasal septum and communicates with the nasal and oral cavities through ducts, the anatomy of which varies by species. The so-called Flehmen response, in which the upper lips are raised and the mouth slightly opens in a characteristic fashion, serves to enhance pheromone perception; active pumping of blood vessels transports solubilised pheromones into the interior of the vomeronasal organ, where they bind to specialised receptors. From there, information regarding the presence of pheromones is transmitted to the accessory olfactory bulb, the amygdala, and ultimately to the ventromedial hypothalamus. Pheromones in canine communication In the dog, olfactory substances are known to play an important role in the pups recognition of the bitch s teats, the formation of the maternal bond between bitch and pups; the recognition of individual animals (mouth, face, anus) and in marking behaviours (paws, urine, faeces). For example, pheromones emitted by fearful animals may have significant negative effects on the stress level of other animals in a variety of situations, such as in waiting and treatment rooms in veterinary hospitals. In contrast, the presence of appeasing pheromones can significantly decrease the effects of anxiety and stress. The role of pheromones in helping to prevent canine behaviour problems The dog appeasing pheromone (D.A.P., renamed as Adaptil ) is an isolate of pheromones the bitch produces in the area of the mammary glands during lactation.

5 The anxiety-reducing properties of this substance affect the behaviour of the adult dog and Adaptil has been shown to be effective both in helping to prevent and manage a range of behavioural issues in the domestic dog. In regard to prevention, the use of Adaptil for the first month after a puppy or a rescue dog arrives in its new home has been shown to help reduce behavioural signs of anxiety. For example, in a study at Lincoln University night time waking and vocalisation in newly homed puppies was shown to be significantly reduced when a Adaptil Diffuser was installed in the new home. In a separate study carried out by Deneberg et al, fitting puppies with an Adaptil Collar at between 8 and 15 weeks resulted in significant beneficial effects on their behaviour, suggesting that in addition to reducing stress, Adaptil may potentially also help increase the capacity to learn. Adaptil has also been shown to be of benefit to dogs in kennels. Studies show a reduction in vocalisation and lowering of overall levels of stress. Studies also show that Adaptil may be of benefit in reducing mild firework fears and fears of travelling or visiting the vet. However, behavioural therapy should also be used in these situations, particularly if the behavioural effects of the fear are significant, and advice should be sought from a qualified behaviourist. Pheromones in feline communication There are 5 feline facial pheromones (F1-F5) that have been identified in cats. The F3 fraction is the pheromone that is deposited by the cat throughout the environment by facial rubbing. It serves to mark out boundaries and passageways and is believed to help the cat feel more secure. The absence of these familiar marks is likely to result in an increase in anxiety. The role of pheromones in helping to prevent feline behaviour problems Synthetic F3 pheromone, Feliway, is recommended for the control of stress, anxiety, urine marking, vertical scratching, loss of appetite, reduced desire to play and reduced interest in interactions. In addition, its use in the support of treatment for medical conditions has been highlighted through the increasing wealth of information detailing the connection between chronic stress and physical disease. Research has clearly shown that chronic stress is a significant factor in the onset and maintenance of disease states as diverse as feline idiopathic cystitis, dermatological conditions and gastrointestinal disorders and the use of Feliway as an adjunct to medical therapy for these conditions is now highly recommended. Feliway can also play an important role in a multimodal approach to the common problem of feline obesity. Recently Feliway has been proven to reduce cat s stress in veterinary consultations. Conclusion Pheromone analogues are important tools in reducing and helping to prevent canine or feline stress and when used in combination with environmental modification or up to date methods of behavioural therapy they present interesting possibilities for effectively influencing undesirable canine or feline behaviours. The ease of applying these pheromones and the absence of known side effects, which can be associated with psychopharmacological interventions, represent significant advantages of this mode of therapy.

6 What is Adaptil What is ADAPTIL Canine appeasing pheromone is released by the dam to support bonding and to comfort and reassure her puppies. This support gives puppies enough con dence to explore and learn about the world around them. This canine appeasing pheromone is proven to have the same comforting in uence on adult dogs. Adaptil is a synthetic copy of this pheromone and is proven to help adult dogs cope in challenging or worrying situations. When used during training and socialisation: Adaptil helps promote learning and helps ensure puppies develop into well-behaved, con dent and resilient adult dogs, thus reducing the likelihood of anxiety-related behaviour problems developing in later life. Dogs need to detect very little of the pheromone for it to elicit the desired response. Due to their unique mode of perception and action, it is impossible for dogs to overdose, become immune or adversely react to pheromones in any way. Adaptil is non-sedative, non -systemic and as such has no contraindications with any other treatment. It is available as a plug-in di user, spray and collar. Pheromones are species speci c. It is thereby impossible for Adaptil to a ect humans or other pets. The effect of Adaptil has been shown in more than 20 studies published in peer-reviewed scientific journals or presented at international conferences (until the end of 2010, under the D.A.P. name).

7 There is an Adaptil solution to every situation PRODUCT USES ADAPTIL DIFFUSER ADAPTIL SPRAY 60ML/20ML ADAPTIL COLLAR RECOMMENDED duration of use Changes to Dogs Environment - New arrivals (baby, pets, etc) - Redecorating - New home + Begin use at least 24 hours prior to changes and use for minimum 1 month Travel Vet visits Grooming Spray Adaptil 15 min before leaving on dog s crate/bandana/bedding. Re-apply every 4-5 hours for long travels. Thunderstorms or Fireworks + (indoor dogs) (outdoor dogs) Begin use at least 24 hours prior to events and use during a week after fireworks, or during the full storms season Staying home alone + (indoor dog) (outdoor dog) Minimum 1 month Crating/Kenneling or Boarding + Continuously while boarded or kenneled Training + Continuously during training Puppy Socialisation (Dog parks, new situations, etc) months, beginning from 7 weeks of age = Product most suited for the situation + = Additional Adaptil products to combine for added support All dogs are unique, and results may vary. You may see improvements in as little as a week. For best results use continuously for 30 days. Adaptil is not recommended for hyperactivity and aggression towards humans or other dogs. Consulting a qualified behaviorist is strongly recommended in any case. Additional behavioural and environmental modifications may be required and advice should be sought from your veterinary practice.

8 Adoption Period Adoption Period Settling into a new home is a stressful and disorientating process for a puppy. siblings and its usual source of comfort and reassurance, the dam. During the days following adoption, disturbance and vocalisation can be a common problem for a puppy and its owner. It is important that steps are taken to help a puppy cope with its new environment without becoming unduly stressed. Preferred Supplement A puppy adopted prior to 12 weeks of age is highly sensitive and its perception and encounters 1. In the same way, shelter dogs are supposed to be less sensitive than puppies, but considering their background (relinquishment, staying in a kennel) the adoption process can also be a tedious and stressful process for them. Environmental enrichment as well as training classes can be very useful for both adult dogs and puppies to help them during the post-adoption period. The trials outlined in this chapter show how Adaptil Adaptil Collar can help reassure puppies after adoption. Please note that even though trials have been done with the collar form, we recommend Adaptil and potentially Adaptil Spray for the adoption period. 1 Scott J P, Fuller J L, Dog behaviour: the genetic basis. Chicago: University of Chicago Press, 1974;

9 A placebo-controlled study to investigate the effect of dog appeasing pheromone (D.A.P. ) and other environmental and management factors on the reports of disturbance and house soiling during the night in recently adopted puppies (Canis familiaris). Taylor K, Mills D S Applied Animal Behaviour Science, 2007; 105, A double-blind, placebo-controlled trial was carried out to investigate the effect of D.A.P. Diffuser on 60 pedigree puppies, aged between 6 and 10 weeks, as they entered their new home. A few days prior to arrival, the new owners were asked to plug in either a D.A.P. or placebo diffuser. Puppies were monitored for a total of 8 weeks following their adoption. Owners were asked to fill in a form assessing disturbances. The effect of the treatment, together with the gender of the puppies, maternal environment, use of puppy crates and experience of owners were included in a general linear model to explain the total number of nights spent disturbing and house soiling. During the trial, it was reported that some adult dogs produced an appeasing pheromone similar to D.A.P. from the base of their ears (Pageat, personal communication). Therefore, 11 puppies that slept with other dogs were removed from the analysis, since they may have benefited from additional pheromone treatment. Results Over 70% of puppies sleeping alone caused disturbance during the first night. The average total number of nights of disturbance over the 8 week period was between 5 and 6 nights, mostly in the first week in the home. D.A.P. significantly improved the gundog breeds - gundogs receiving the placebo cried for a median of 9 nights, while those receiving D.A.P. cried for a median of 3 nights (p=0.003). No effect on house soiling was seen. Conclusion This study suggests that, when puppies are going to homes with no other dogs, D.A.P. may help to reduce the likelihood of prolonged disturbance at night, particularly if the puppy is a large breed dog. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Adoption Period

10 Efficacy of dog appeasing pheromone (D.A.P. ) in reducing stress associated with social isolation in newly adopted puppies. Gaultier E, Bonnafous L, Vienet-Legue D, Falewee C, Bougrat L, Lafont-Lecuelle C, Pageat P Veterinary Record, 2008; 163, In this triple-blinded trial 66 puppies were adopted from a pet shop. 32 were fitted with a D.A.P. Collar and 34 with a control collar, at random when they arrived at the pet shop. On the day they left the shop the collars were replaced to ensure the release of D.A.P. was consistent during the following evaluation period. Owners were contacted by telephone 3 and 15 days after they had adopted a puppy to obtain information about integration into the family, nuisance or attention seeking behaviours shown at night and signs of distress when the puppy was socially isolated, during the day. The trial was randomised and triple-blinded. Results All the isolated puppies in the control group vocalised during the first night, with more than 30% still causing disturbance by night 15. In comparison, those wearing D.A.P. Collars showed significantly lower levels of vocalisation on the first night (p 0.001), with vocalisation ceasing completely from night 5. Other signs of distress were also significantly lower in the D.A.P. by day 3 and throughout the rest of the study (p 0.001) D.A.P. Group Control Group Number of puppies Nights after adoption Numbers of the 34 control puppies and 32 puppies wearing a dog appeasing pheromone (D.A.P. ) impregnated collar that caused disturbances at night on successive nights after they were adopted Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Adoption Period

11 30 25 *** D.A.P. Group Control Group *** Number of puppies *** ** *** 5 ** NS * NS Vocalisation Contact seeking behaviour Exploratory behaviour Whining Whining and howling Scratching at door Direct contact with owners Wandering Moving or destroying objects Numbers of the 34 control puppies wearing a dog appeasing pheromone (D.A.P. ) impregnated collar that caused different types of disturbances when left alone at night on day(s) 0, 3 and 15. NS, P>0.01, *0.05<P<0.01, **0.01<P<0.001, ***P Conclusion In this trial, D.A.P. Collars quickly and effectively reduced several known stressrelated behaviours commonly seen following adoption (in particular vocalisations and contact seeking behaviour), as soon as 3 days after introduction to the new home. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Adoption Period

12 Efficacy of dog appeasing pheromone (D.A.P. ) in reducing behaviours associated with fear of unfamiliar people and new surroundings in newly adopted puppies. Gaultier E, Bonnafous L, Vienet-Legue D, Falewee C, Bougrat L, Lafont C, Pageat P Veterinary Record, 2009; 164, In this triple-blinded trial 66 puppies were adopted from a pet shop. 32 were fitted with a D.A.P. Collar and 34 with a control collar, at random when they arrived at the pet shop. On the day they left the shop the collars were replaced to ensure the release of D.A.P. was consistent during the following evaluation period. Owners were interviewed by phone 3 and 15 days post adoption and questioned about how their puppy had reacted in specific situations, such as when encountering new or unfamiliar objects or people. Results Regardless of date, the control puppies were more fearful than those wearing D.A.P. Collars, with significant differences still observed by day D.A.P. Group Control Group Number of puppies * * ** * * ** * 5 0 Day 3 Day 15 Signs of fear facing neutral unfamiliar people at home Day 3 Day 15 Fear reactions when walking outside Day 3 Day 15 Signs of fear facing new objects Day 3 Day 15 Signs of fear after an order by the owner Numbers of dog appeasing pheromone (D.A.P ) treated and control puppies that showed different types of behaviours in response to fear-elliciting situations, on days 3 and 15 after they adopted. *0.05>P 0.01, **0.1>P 0.05 Day 3 Day 15 Signs of fear facing unfamiliar people Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Adoption Period

13 Conclusion In this trial, puppies wearing a D.A.P. Collar learnt to cope with stressful situations more quickly than those wearing the control. By reducing the number of exposures required to habituate a puppy to a stimuli, fitting a D.A.P. Collar is likely to make the process of settling a puppy in a new home faster and easier for the puppy and the owner. This trial also backs up previous research and suggests owners should continue to use the collars to maintain their positive effects post adoption and help ensure correct socialisation. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Adoption Period

14 Recommendations for Use: Collecting the puppy or dog from the breeder Fit an Adaptil Collar to the puppy or dog on collection. Create a pleasant association with the car whilst stationary, i.e. give small bits of food and play with the puppy in the car before travelling. Adaptil Spray can also be used to give added reassurance during the first car journey to the new home. Adaptil Spray should be applied to a box or crate in the car at least 15 minutes before introducing the dog to allow alcohol to evaporate. On long journeys this may need to be re-applied every 4-5 hours (each time, owners should wait 15 minutes before re-introducing the dog to the area). Settling in a new home At least several hours (ideally 24 hours) before the new puppy/dog arrives plug in an Adaptil Diffuser at floor level in the room where the dog will sleep and spend the most time. The diffuser should be switched on continuously for at least 4 weeks and the refill replaced as required. Adaptil Diffuser can be used alongside Adaptil Collar and Adaptil Spray for additional support. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Adoption Period

15 Socialisation and Training Puppy classes, when properly carried out, can be very helpful, as correct training while the dog is in the more receptive socialisation phase, dramatically increases the likelihood that the dog will stay in its new home for life 1,2. However, it is also vital that steps are taken to ensure these early experiences are positive and that the dog is able to cope appropriately with each new stimulus 1,3. Preferred Supplement Puppy Socialisation A young dog must not be overwhelmed throughout this period, as both an under-socialised puppy and/or one that becomes highly stressed during develop stress-related behavioural problems in later life. These include general nervousness, noise phobias, separation anxiety and fear aggression. Supplement Adaptil Collar and Adaptil signs of stress in puppies during its socialisation phase but also in adult dogs following publications. 1 Duxbury M M, Jackson J A, Line S W, et al. Evaluation of association between retention in the home and attendance at puppy socialisation classes. Journal of the American Veterinary Medical Association, 2003; Seksel K, Mazurski E J, Taylor A, Puppy socialisation programs: short and long term behavioural 3 American Veterinary Society of Animal Behaviour position statement on socialization. Available at:

16 Evaluation of the effectiveness of synthetic D.A.P. (dog appeasing pheromone) in reducing levels of arousal and improving learning in puppy classes. Graham D, Mills D S, Bailey G Proceedings of the Companion Animal Behaviour Therapy Study Group, A double-blind, placebo-controlled trial evaluated the effect of dog appeasing pheromone (D.A.P. ) on puppy behaviour, levels of arousal and learning in puppy school socialisation and training classes. Sixty one puppies under 20 weeks of age enrolled on a 6 week course. Each class had a minimum of 3 and maximum of 8 puppies. In the treatment groups, 2 D.A.P. Diffusers were plugged in approximately 30 minutes before the first class and located separately but immediately behind the owners seating. Levels of arousal were determined from both acoustic and behavioural data from weeks 1 to 5 at 3 different venues. Changes in behaviour were assessed via video analysis during periods of free interaction in weeks 1 and 5 and learning was assessed at week 5 by the trainer in 3 different exercises (sit, recall and walking on a loose lead). Results The frequency of barking in the D.A.P. group was significantly lower than in the placebo group (p=0.004). There was a large increase in puppy play in the placebo group which suggests that the D.A.P. group was generally less aroused. Within the treatment groups, levels of exploratory sniffing (p = ) and pawing (p = ) were significantly higher in the placebo group, whereas rapid withdrawal was higher in the D.A.P. group (p = ) as was the tendency to roll over (p = ) suggesting that the D.A.P. group tended to exhibit more social appeasing behaviour than the placebo group. Although no significant differences were found between the groups when assessed on the ability to sit, recall and walk on a loose lead, 74.6% of puppies in the D.A.P. group compared with 68% of puppies in the placebo group gained the higher grades. Conclusion In this trial, D.A.P. Diffuser was effective in significantly reducing and maintaining lower levels of vocalisation in puppy classes. Puppies in classes using the D.A.P. Diffuser were less aroused and showed more appeasing behaviours. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Puppy Socialisation

17 Effects of dog appeasing pheromone (D.A.P. ) on anxiety and fear in puppies during training and on long-term socialisation. Denenberg S, Landsberg G M Journal of the American Veterinary Medical Association, 2008; 233, Forty five puppies between the ages of 3 and 4 months were split into 4 separate puppy classes - 2 for large breeds, 2 for small breeds. 1 large breed class and 1 small breed class were fitted with D.A.P. Collars, while the other 2 classes were fitted with placebo collars. Puppies attended their classes once a week for 8 weeks and were taught by the same trainer throughout. Before the first class and after each subsequent class the trainer and owners completed a questionnaire evaluating the puppies learning, fear, excitability, interactions and progress. Each question was ranked on a 5 point scale. As the D.A.P. Collar lasts for 4 weeks, each was replaced once during the 8 week study period. Follow-up telephone surveys were performed at 1, 3, 6 and 12 months after the classes ended to ascertain the owners perception of their puppies behaviour. Results Puppies in the D.A.P. Collar group displayed a significantly lower degree of fear and anxiety, longer and more positive interactions during play, and better response to training. The data from the telephone surveys indicated that the puppies in the D.A.P. Collar groups were significantly better socialised (p<0.01) and adapted faster in new situations and environments. Socialisation score Socialisation score 4,5 4, ,5 3, ,5 2,5 2,0 2,0 1,5 1,5 1,0 1,0 0,5 0,5 0,0 0,0 Median socialisation scores (short term) Median socialisation scores (short term) * * * * Months after study Months after study Dog Appeasing Pheromone collar Dog Appeasing (n-24) Pheromone collar (n-24) Placebo collar (n-21) Placebo collar (n-21) * * significant difference Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Puppy Socialisation

18 Median Median socialisation socialisation scores scores (long (long term) term) Socialisation score Socialisation score 3,5 3, ,5 2,5 2,0 2,0 1,5 1,5 1,0 1,0 0,5 0,5 0,0 0,0 * * * * Months Months after after study study Dog Dog Appeasing Pheromone collar collar (n-24) (n-24) Placebo Placebo collar collar (n-21) (n-21) * * significant difference Median socialization scores for puppies that attended training classes for an 8-week period. Puppies were assessed by their owners at various time points during the 12 months after classes concluded, according to a 5-point scoring system (0 = very bad; 1 = bad; 2 = impartial; 3 = good; and 4 = very good). Conclusion In this trial, the D.A.P. Collar demonstrated both short and long-term beneficial effects on puppy behaviour. D.A.P. was useful in reducing degrees of anxiety and arousal in puppies attending training classes. Furthermore, the use of D.A.P. during the classes resulted in improved socialisation of dogs up to 1 year after classes concluded, helping puppies develop into balanced and well-trained adult dogs. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Puppy Socialisation

19 Efficacy evaluation of D.A.P. diffuser versus placebo diffuser for guide dogs completing the final stage of training program leading to graduation as a working guide dog with a visually impaired person. DePorter T L, Landsberg G M, Beck A. Proceedings of the Companion Animal Behaviour Therapy Study Group, (Michigan, USA) A double blind placebo-controlled study was conducted at Leader Dogs for the Blind (LD) to ascertain how D.A.P. would enhance training and graduation success of professionally trained guide dogs. Following 16 months of rigorous and selective training, the dog is assigned to a visually impaired recipient student. The student/ dog team lives together during a 26-day residence training program to become one of the 250 teams who graduate from LD annually. The transition from living in a kennel to dormitory plus assignment to a new caretaker is an abrupt and dramatic lifestyle change for those dogs. To enhance adaptation and facilitate bonding, D.A.P. diffusers were provided during this pivotal period. Thirty-nine student/dog teams were enrolled and a D.A.P. or a placebo diffuser was plugged in each dormitory room. Each dog was in its room at night and during break periods (estimated hours/ day). LD trainers assessed bond development ( turnover ), socialization, adaptability, distractibility and obedience. Results D.A.P. diffuser group graduation rate was 17/17 (100%) compared to the placebo group graduation rate of 17/21 (80.9%) with 4 placebo dogs failing due to behavior related causes. One dog became ill and was removed from the program. The graduation rate difference between the treatment groups did not reach statistical significance (p=0.11) (Fisher exact test), however, all 4 of the dogs failing due to behavior were from the placebo group (p=0.11). This finding is important considering the cost of training each guide dog exceeds $40,000USD so the cost of behavioral related failure for 4 dogs at this stage of training exceeds $160,000USD. Many factors, which necessarily influence successful graduation of a guide dog were assessed. Statistical analysis did not reveal a treatment effect for individual assessment criteria. Further, comparison of trainer trait assessments confirmed that no single factor predicts graduation, however, trainer s overall assessment of candidate as compared to the ideal LD by visual analogue scale score on a 10 cm line (7.92 versus 6.5) did correlate with successful graduation (p= 0.013) (ANOVA). Conclusion The D.A.P. group had a 19.1% higher graduation rate indicating D.A.P. improved the rate of graduation success for these highly selected and intensively trained dogs though DAP was used only during final stage of training to become working guide dog. D.A.P. is known to be beneficial for dogs that suffer from anxiety. The results of this study suggest D.A.P. may be beneficial for helping even well-trained and emotionally stable dogs to cope with training stresses and lifestyle challenges. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Puppy Socialisation

20 Effectiveness of dog appeasing pheromone (D.A.P. ) collars applied during the socialization period for prevention of development of fear and anxiety. DePorter T, Beck A, and Landsberg G Proceedings of the 9th International Veterinary Behaviour Meeting, Lisbon, Portugal, 2013;91-92 This double-blind placebo-controlled D.A.P. collar study included 62 seven-weekold future guide dogs. 1 Sets of 3 collars (DAP or placebo) were randomly assigned and applied consecutively from 7-19 weeks of age. Puppy raisers completed C-BARQ 2 at 19weeks, 6 & 12 months, and Leader Dog (LD) survey at 3 & 6 months. One C-BARQ section: fear and anxiety, evaluates response to sounds, objects, persons or situations on a five-point scale (0-4). Holding these well-trained dogs to a high standard, a perfect response required no signs of fear or anxiety and any fearful responses were considered poor. Greater than 90% of all subjects achieved perfect for 9 questions. The remaining 10 questions were analyzed by Chi square or Fisher Exact test to compare the number of D.A.P. and placebo-subjects achieving a perfect response at 19w, 6m, 12m and all time points combined (C). Results When compared to placebo, more D.A.P. subjects achieved perfect response to the following: approach by unfamiliar dog at 12 m (p=0.038); sudden or loud noises: 12m (p=0.064), C (p=0.028); and first exposure to new situations (veterinarian, car, elevator) at 19w (p=0.022), 6m (p=0.046) and C (p=0.011). More placebo-subjects scored perfect response to unfamiliar objects on sidewalk at 19w (p=0.029), and bathing at 12m (p=0.020) and C (p=0.044). On LD survey at 3m & 6m, more D.A.P. subjects achieved perfect response to movement at 3m (p=0.0081) and 6m (p=0.090); children 6m (p=0.048), animals 3m (p=0.060) and noises 3m (p=0.072) while there was no evidence placebo-subjects did better. % of perfect response P=0.075 P=0.064 Placebo D.A.P weeks 6 months 12 months The response to sudden or loud noises (e.g. vacuum cleaner, car backfire, road drills, object being dropped, etc) in D.A.P. or placebo group. Conclusion: When applied during the socialization period, D.A.P. was useful in reducing anxiety and fear in puppies during and even beyond the treatment period. 1. Leader Dogs for the Blind ( Rochester, MI USA 2. C-BARQ (Canine Behavioral Assessment and Research Questionnaire) Center for the Interaction of Animals and Society of the University of Pennsylvania. (

21 Recommendations for Use: During puppy socialisation Fitting an Adaptil Collar throughout the socialisation period (from 3 until 12 to 16 weeks) has been shown to dramatically influence a puppy s development and help it grow into a well-behaved and confident adult dog. Thus, wearing an Adaptil Collar during this period will help prevent fears and stress which may lead to anxiety-related behavioural problems later in life. It is recommended that the Adaptil Collar is fitted at first vaccination and another provided to be fitted 4 weeks later. The collar only releases the pheromone when it is warmed by the dog s body heat. Therefore, it should be checked regularly to ensure it has not become loose. It is also advisable to check that the collar has not become too tight as the puppy grows. Remove the collar before bathing or shampooing and replace it after the dog s coat is dry. For puppies attending classes, in addition to Adaptil Collar, an Adaptil Diffuser may be plugged in the room where the puppy classes take place. The diffuser should be switched on at least several hours (ideally 24) before the class and left on until the class is complete. During training sessions As intensive training for future working dogs may be extremely stressful, wearing an Adaptil Collar during this period will help prevent fears and make the dog more responsive to the training. The same recommendations as for puppies (see above) apply to adult trained dogs. In particular, for dogs trained to swim or jump in swimming pools, the collar should be removed and replaced after the dog s coat is dry. In addition to Adaptil Collar, an Adaptil Diffuser may be plugged in the room where the training sessions take place. The diffuser should be plugged / switched on at least several hours (ideally 24) before and left on until the session is complete. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Puppy Socialisation

22 Kennels and Rescue Centres The kennel environment can be very stressful for dogs and most require support while they adapt. During this adaptation phase dogs often show a variety of stress-related signs including: Anorexia Excessive barking Fear Gastrointestinal problems Aggression Excessive locomotion Self-mutilation Preferred Supplement Kennels and Rescue Centres Not only does stress compromise welfare standards, but it can also exacerbate existing and/or contribute to the occurrence of new stress-related behaviour problems, including a range of stereotypic (displacement) behaviours, such as shadow chasing. In most cases this behaviour is temporary, but in the most severe cases this behaviour can become a permanent habit which, once After aggression, stress-related behaviour problems are the most common reason for a healthy dog to be euthanised. After adapting to kennels, a similar situation is commonly observed when the dog re-enters the home environment. Again, the dog may show temporary stress-related behaviour while it adapts to the new situation. Unfortunately, it is believed that this is the reason for many people returning dogs to rescue centres in the weeks following adoption. 89.7% of people who return a dog to a shelter do so because the animal 1. Adaptil Collar and Adaptil signs of stress in kennelled dogs, as supported by the following publications. 1 Wells D L, Hepper P G, Prevalence of behaviour problems reported by owners of dogs purchased from an animal rescue shelters. Applied Animal Behaviour Science, 2000;

23 The use of the D.A.P. Collar to reduce stress during training of police dogs (Canis familiaris): a preliminary study. Schroll S, Dehasse J, Palme R, Sommerfeld-Stur I, Lőwenstein G Current Issues and Research in Veterinary Behavioural Medicine. Proceedings of the 5th International Veterinary Behaviour Meeting, Minneapolis, USA, 2005; At 16 to 22 months of age, police dogs in Austria are taken from their home environment to start an intensive 15 week training course. They experience isolation and separation anxiety with signs including excessive barking and howling at night, increased excitement, lack of concentration at work, weight loss, diarrhoea and salivation. In this trial, 9 male dogs (2 German Shepherds, 4 Malinois, 2 Dutch Herders and 1 Giant Schnauzer) between 19 and 22 months of age were divided into 2 random groups. 5 dogs were fitted with a D.A.P. Collar and 4 were fitted with a placebo. Physical and behavioural signs (appetite, salivation, diarrhoea, panting, destructiveness, vocalisation at night and psychological condition) were recorded daily by the owner. Results From the first training day, all dogs were quiet during the night. Only 1 dog from each group barked during the 4 weeks and this was for a few times for less than 10 minutes, without vocalisation reaction from the other dogs. In the morning, the dogs were relaxed. None had diarrhea, salivation or appetite loss. The weight of the dogs in the D.A.P. Collar group remained stable whereas the dogs in the placebo group lost weight, which could be considered a sign of a possible chronic stress. Conclusion Although performed on a limited sample size (9 dogs), this preliminary trial suggested that the D.A.P. Collar, when used in conjunction with owner education, might reduce the signs of stress in young adult police dogs during training. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Kennels and Rescue Centres

24 Adaptive mechanisms in dogs adopted from shelters: a behavioral assessment of the use of a synthetic analogue of the canine appeasing pheromone. Osella M.C., Bergamasco L., Odore R., Beck A., Gazzano A. Dog Behavior, , pp doi /db.v1i2.10 Adaptation to a new socio-environment might represent a very hard step for sheltered dogs, because of a higher level of difficulty in coping with unfamiliar conditions, possibly limiting the success rate of rehoming. The aim of this prospective open-label study was to investigate the effects of the Dog Appeasing Pheromone (Adaptil ) in dogs re-homed from a private rescue shelter. Thirty-two healthy dogs (16 puppies and 16 adults), of any breed or mix-breed, aged between 1 and 7 years for adults, 2 and 6 months for puppies, were included. At adoption, Adaptil Diffusers were given to owners to plug into their home and a replacement refill to be changed at D28. No instructions were given to the new owners to prevent behavior problems in their newly adopted dog or puppy. The owners were interviewed at 28 and 56 days at the shelter. They were asked to rate the frequency of several behavioral signs (using a four-point scale) and the evolution of each behavioral sign from D28 to D56, on a five point scale. After 56 days, the trial ceased. Results Significant decreases from D28 to D56 were observed in adult dogs for wandering in the house restlessly (p=0.022) and hiding fearfully in protected corners (p=0.033), whereas in puppies treatment with DAP significantly (p<0.05) improved the reaction towards unfamiliar dogs (p=0.048) and wandering in the house restlessly (p=0.022). In both adults and puppies a significant improvement in interaction with owners was observed. In particular, looking continuously for the owners and following the owners everywhere like a shadow were significantly improved (p= and respectively) in adult dogs. Separation reactions revealed a significant decrease (p<0.05) and in puppies the tendency to vocalize in absence of the owner was also significantly reduced (p=0.0029). Both adults and puppies showed a decreased tendency to wake suddenly in the night (p=0.024 and p=0.026 respectively) and wander around the home (p=0.012 and p=0.026 respectively). In contrast, for house-training no significant difference was reported in adults, whereas for puppies there was a significant decrease (p<0.05) in the mean scores for urination and/or defecation wherever in the house and after coming home. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Veterinary Practice Use

25 Data regarding the overall assessment suggested a significant improvement in all the efficacy variables considered in the study. The analysis of owners degree of satisfaction at the final visit showed that Adaptil treatment was considered successful by 84.4 % of owners against 53.1% at D28 visit, while the percentage of unsatisfied owners (46.9%) at D28 decreased to 15.6% at D56 (p<0.0001). No dogs in the 32 included returned to the shelter, according to a phone follow up at one month, two months and 6 months after adoption. Owner s degree of satisfaction treatment SATISFIED DISSATISFIED Percentage D28 D56 Conclusion Results suggest that the use of Adaptil might improve dogs adaptability throughout the first weeks following adoption and can be considered a useful tool for reducing stress in re-homed dogs. This could ultimately help to decrease the return rate to the shelter. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Veterinary Practice Use

26 Efficacy of dog appeasing pheromone (D.A.P. ) in reducing stress and fear related behaviour in shelter dogs. Tod E, Brander D, Waran N Applied Animal Behaviour Science, 2005; 93, A D.A.P. Diffuser was plugged into a socket above the internal pens in a kennel block in a public animal shelter in Scotland. 37 treatment and 17 control dogs were assessed using 2 temperament tests associated with fear, separation and excitable behaviour, at D0 and D7. An ethogram was used to identify relaxed, fearful or anxious behaviours. Results Mean barking amplitude (p<0.001) and frequency (p<0.04) were significantly reduced in dogs exposed to the D.A.P. Diffuser for 7 days, though peak values were not significantly altered. There was also a significant reduction in the mean barking amplitude of dogs during the 1 minute recovery period, following a distraction (people walking steadily along the passageway) at D7. After 7 days of exposure to D.A.P., there were significant differences in resting (p=0.03), barking (p<0.04) and sniffing (p=0.01) frequency in response to a friendly stranger. 90 Placebo group at 7 days D.A.P. Group at 7 days Mean sound pressure level (L eq ) in db Recovery period following test (seconds) Mean sound pressure level (L eq ) over a one minute recovery period, for the placebo group at day 7 and the D.A.P. treatment group at day 7, measured in db. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Kennels and Rescue Centres

27 Barking frequency over a 1 minute period Barking at baseline (day 0) and final day (day 7) recording sessions Day 0 Day 7 0 Day 0 Day 7 Barking frequency in dogs at day 0 before exposure to D.A.P. and at day 7 following continuous exposure to D.A.P.. n = 37 (in response to friendly stranger test) Conclusion In this trial, D.A.P. Diffuser helped reduce some behavioural indicators of stress in dogs in kennels, but allowed normal behavioural responses to distractions in the local environment. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Kennels and Rescue Centres

28 Efficacy of dog appeasing pheromone (D.A.P. ) in reducing stress related responses in rescue shelter dogs. Barlow N, and Goodwin D Proceedings of the Companion Animal Behaviour Therapy Study Group, 2009 A double-blind placebo-controlled trial investigated the effect of D.A.P. Collars on reducing stress-related behaviours over a 10 day period following the admission of 90 dogs to a dog re-homing centre in the UK (31 D.A.P. Collars, 29 placebo collars, 30 control - no collars). The dogs behaviour was observed for 10 minutes on days 2 and 10 after admission using 2 video cameras located at the front and rear of the kennels. A variation on the ethogram used by Tod et al. (2005) was utilised to identify behaviours suggestive of relaxation, fear or anxiety. Results The D.A.P. group spent less time locomoting on days 2 (p<0.05) and 10 (p<0.05) compared to the placebo group and the control group and longer lying on day 10 (p<0.01) compared to the placebo group. The D.A.P. group also displayed a lower frequency of barking on day 2 (p<0.01) compared to the placebo group and the control group. Mean duration (s) D.A.P. Collar Placebo Collar No Collar Mean frequency count Time engaged in locomotor behaviour during the 10 day period 0 Frequency of barking during the 10 day period Conclusion In this trial, the D.A.P. Collar was an effective tool in reducing some of the stressrelated behaviours known to occur in dogs in the shelter environment including excessive locomotion and vocalisation. The D.A.P. Collar was also effective in promoting behaviour suggestive of relaxation such as lying down. D.A.P. did not affect normal reactions to activity going on around the dog but the reduction in frequency seen suggests that the dogs recovered more quickly after a challenge. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Kennels and Rescue Centres

29 Recommendations for Use: Helping dogs cope with the kennel environment An Adaptil Collar should be fitted to the dog as soon as possible (ideally before introduction) to prevent the dog becoming stressed in the kennel environment. For best results, an Adaptil Collar should be fitted on any new dog coming into the kennel. The collar only releases the pheromone when it is warmed by the dog s body heat. Therefore, it should be checked regularly to ensure it has not become loose. Alternatively, the Adaptil Spray (applied on the dog s bedding, at least 15 minutes before introducing the dog in the area, to allow alcohol to evaporate) can be used as a temporary measure lasting 4-5 hours. If the dog is already highly aroused then the effects will be more limited, so, in situations known to be challenging, it is advisable not to wait until the animal shows signs of stress. N.B. Adaptil is not a sedative and will allow dogs to show normal reactions to things happening around them, such as a person walking past the kennel. However, this response may be reduced in duration and intensity. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Kennels and Rescue Centres

30 Separation -Related Behaviour Problems Separation-related behavioural problems in dogs occur only when the dog is separated from or denied access to its owner. Typical behaviours can include destructiveness, excessive vocalisation and house soiling, although some dogs may hyperventilate, vomit, salivate, urinate or defecate. After aggression, separation-related disorders are the most common behavioural problem for which a dog is referred to a behaviour specialist 1. Preferred Supplement Separation Problems and may lead to dogs being re-homed. This undesirable behaviour may also have legal implications due to the anti-social nature of excessive vocalisation. Separation anxiety is challenging for veterinarians to resolve in practice and every attempt should be made to support the dog during the socialisation period and each time there is a change in the dog s routine to avoid problems such as separation anxiety later in the dog s life. This will make it less likely Alternative socialisation. In adult dogs, separation anxiety requires behavioural therapy to resolve the situation fully. The next publication details how Adaptil related disorders. 1 Borchelt and Voith (1982), Wright and Nesselrote (1987), Landsberg (1991), McCrave (1991), Pageat (1995), Overall (1997), Simpson (2000), Gaultier (2001)

31 Comparison of the efficacy of a synthetic dog appeasing pheromone (D.A.P. ) with clomipramine for the treatment of separation-related disorders in dogs. Gaultier E, Bonnafous L, Bougrat L, Lafont C, Pageat P Veterinary Record, 2005; 156, Sixty seven dogs showing signs of distress when separated from their owners were recruited at veterinary clinics in France, Italy, Spain and Switzerland. The dogs were randomly assigned to two treatment groups: group 1 (36 dogs) had a D.A.P. Diffuser and placebo capsules, group 2 (31 dogs) had clomipramine capsules and a placebo diffuser. The comparability between the 2 treatment groups has been checked: most of the separation-related signs were well balanced between both groups except for defaecation/urination and feeding problems (see figure). The treatment ran for a mean period of 28 days, and included a behavioural modification plan. Behavioural examinations were performed by the veterinarian on D0 and D28, and the owners were contacted by telephone by the vet between D12 and D18. The monitoring form recorded how many times and for how long the owner had been absent on each day and what signs the dog had exhibited. In addition, tolerability and compliance were recorded. Number of dogs % 73% 67% 67% * 67% 40% 22% 23% 37% 43% D.A.P. Group Clomipramine Group 33% 57% 22% 41% 30% 0 Destruction Vocalisation Defaecation/ urination Sleeping problems Excessive licking Feeding problems 13% Hypersalivating/ vomiting Lack of adaption to change Comparability between 2 groups: initial frequencies of the separation-related behaviours shown by the 57 dogs treated for 28 days with either clomipramine (CLO) or dog-appeasing pheromone (DAP). * Significant difference, P<0-05 Results The undesirable behaviours decreased in both groups, but the overall assessment by the owners indicated that there was no significant difference between the 2 treatments (p<0.05). Note: only 57 dogs completed the trial (10 were excluded for various reasons, well-balanced between both groups). However, there were fewer undesirable events in the dogs treated with the pheromone, and the administration of the pheromone appeared to be more convenient. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Separation-Related Behavioural Problems

32 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 35% 40% 25% Destruction 56% 29% 12% Defaecation/urination 28% 50% 11% 11% Vocalisation 63% 32% 9% Destruction 33% 42% 25% Defaecation/urination 25% 40% 35% Vocalisation Disappeared Reduced No change Worse Clomipramine DAP Effect of treatment with clomipromine (CLO) or dog-appeasing pheromone (DAP) for 28 days on the main separation-related disorder in the dogs Conclusion In this trial, D.A.P. Diffuser, in combination with a behavioural plan, could quickly reduce the undesirable behaviours exhibited by dogs suffering from separation-related problems and hyper-attachment. The effects of the D.A.P. treatment were not inferior to the clomipramine. In addition, D.A.P. Diffuser did not 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. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Separation-Related Behavioural Problems

33 Recommendations for Use: Clinical management of separation-related behavioural problems An Adaptil Diffuser should always be used alongside behavioural therapy (see details below) to promote learning and help the dog adapt to spending time alone. The diffuser should be plugged in, preferably at floor level next to where the dog is going to sleep and spend time while alone. However, if the dog is very destructive it is advised that the diffuser is out of reach, for example, the other side of a stair gate. The diffuser should be switched on continuously until the dog s condition has stabilised and remained stable for at least 4 weeks. A refill should be replaced as required. To reduce early signs of separation problems or to help young dogs cope with staying home alone The dog should be provided with a place to be safe when the owner is away. An Adaptil Diffuser should be plugged in, preferably at floor level next to where the dog is going to sleep and spend time while alone (see above recommendation). The diffuser should be switched on continuously for at least 4 weeks. If no response is seen within four weeks, the dog should be referred for behavioural therapy. The process of leaving the dog should be made very matter of fact and the dog should not be fussed over or given any added attention. When returning home, the owner should only greet the dog briefly and without too much excitement. Only reward the good behaviour once the dog has settled down. Never punish the dog for inappropriate behaviour during the owner s absence. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Separation-Related Behavioural Problems

34 Sound sensitivities Sound sensitivities are a common problem in pets with at least 49% of dogs major trigger for owners to seek help. Other noise sensitivities include fear of thunderstorms, gunshots, engine noises, etc. They can range from mild fear to real phobia, often at the last minute. However, noise fearful dogs can be activities of both pets and owners. Noise Fears A fear response is natural and protects an individual from harm and helps them avoid situations where they may get hurt or be in danger. However, from a welfare point of view, both veterinary professionals and pet owners should be Adaptil in conjunction often progress to become a more serious sound sensitivity, eg thunderstorms. Noise Phobia An animal with clinical signs will start to panic at the slightest noise and the reaction is always a sudden, extreme, excessive response which may be persistent and can interfere with normal behaviour. A noise phobic dog may n and the nights drawing in. Such a dog is also more likely to panic, possibly causing injury to both themselves, people and other pets, become aggressive, damage property or run away. Noise sensitivities (fears and phobias) can be treated successfully through a process of desensitisation and counter-conditioning, in conjunction with sensitivity, it is better to anticipate the therapy so that it is carried out when therapy. Sound sensitivity scale Drs Jon Bowen and Jaume Fatjo have developed a validated scale to evaluate the extend of a dog s sound sensitivity. It consists of 5 short question blocks that can be completed online. An information sheet is generated giving a score on the dog s sound sensitivity and suggesting management techniques to help the dog cope. This scale can be found at Preferred Supplement Alternative Sound Sensitivities 1 Blackwell E, Casey R, Bradshaw J, Firework Fears and Phobias in the Domestic Dog - Available online at (assessed Jan )

35 Evaluation of dog appeasing pheromone (D.A.P. ) as a potential treatment for dogs fearful of fireworks. Sheppard G, Mills D S Veterinary Record, 2003; 152, Thirty dogs that showed signs of fear in response to fireworks participated in an open clinical trial to assess whether dog-appeasing pheromone could alleviate their behavioural signs. There were 16 males (11 neutered) and 14 females (12 neutered) and equal numbers of mixed breed and pure breed dogs. The dogs were aged from 14 to 165 months (13 years 9 months) and the duration of the problem ranged from 1 month to years. During the trial, 10 owners administered anxiolytic or sedative medication to their dogs on at least 1 occasion. However, all the dogs experienced at least 4 firework events and results only refer to the responses displayed without other medication. Owners were asked to ignore any fearful behaviour, act normally and not to punish their dogs under any circumstance. The treatment was delivered continuously via a diffuser plugged as close as possible to the dog s usual resting area at home. The owners identified the behavioural signs of fear that their dogs normally displayed in response to the loud noises, rated their frequency and assessed the overall severity of their responses and the evolution, on a weekly basis. These were repeated at the final assessment and the owners also rated the change in their dog s responses. Results There were significant improvements (p=0.05) in the owners rating of 9 of the 14 behavioural signs of fear that were examined and a decrease in median frequency of 13 of the 14. In addition, 22 of 30 owners reported a significant (p<0.01) lower overall fear rating. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Sound sensitivities

36 3.0 * Baseline assessment Final assessment *** *** *** *** *** *** Median frequency rating * * Runs around (n=8) Hides (n=22) Destructive (n=11) Pants (n=29) Elimination (n=8) Trembles (n=28) Salivates (n=12) Cowers etc (n=23) Vocalises (n=14) Seeks owner (n=20) Vigilance (n=17) Startle (n=6) Restless (n=16) Bolts (n=8) Owners perceptions of the frequency of each sign at the baseline and final assessments. * P<0.05, ** P<0.01, *** P<0.005 Conclusion While this was not a placebo controlled trial, there was a reported improvement in the dog response to firework exposure in the presence of D.A.P. Diffuser when the owner followed some basic guidelines. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Sound sensitivities

37 Retrospective analysis of the treatment of firework fears in dogs. Mills D S, Gandia Estelles M, Coleshaw P H, Shorthouse C Veterinary Record, 2003; 153, A retrospective study was carried out to assess the treatment outcomes from owners seeking assistance with their dog s fear of fireworks from a small animal clinic in the UK. 4 treatment options were offered a desensitisation CD, a D.A.P. Diffuser, a desensitisation CD in combination with a D.A.P. Diffuser and psychoactive medication (acepromazine or diazepam). The owners of healthy pets were able to choose from these treatment options, in consultation with their veterinary surgeon, and were given generic advice about how to manage the dog during the firework season. 200 of these clients were then contacted by post 3 to 6 months later and asked to fill in a questionnaire. Owners were required to rate the frequency of 14 target behaviours before and after treatment and were questioned on compliance and their responses to fearful behaviour, i.e. ignoring the dog when it became anxious. Forty eight useable questionnaires were returned, relating to 27 dogs and 21 bitches (pure breeds and cross breeds) of 3 to 13 years of age. 14 owners used a psychoactive medication (alone or in combination), 32 used the CD and 32 used the D.A.P. Diffuser (with 21 using CD and D.A.P. ). Results The use of a CD desensitisation programme alongside D.A.P. was effective in reducing a large number of signs associated with the fear of fireworks. However, the use of D.A.P. alone had a greater effect than any other single treatment on reducing the tendency to hide, vocalise or be startled. Use of the CD was associated with a greater reduction in restlessness. There was an apparent lack of effect of psychoactive medication. However, this could be attributed to poor owner compliance in providing behavioural therapy and following instructions alongside giving a drug. Conclusion In this trial, D.A.P. Diffuser was shown to support desensitisation with a CD and reduce some signs of fear during firework exposure. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Sound sensitivities

38 A prospective study of two self-help CD based desensitisation and counter-conditioning programmes with the use of dog appeasing pheromone (D.A.P. ) for the treatment of firework fears in dogs (Canis familiaris). Levine E D, Ramos D, Mills D S Applied Animal Behaviour Science, 2007; 105, Fifty four owners of dogs with a fear of fireworks were recruited for an 8 week period of training. The dogs were separated into 2 treatment groups, each using a different CD based programme (Fear of Fireworks and Sounds Scary *), and both recommending the use of a D.A.P. Diffuser. After implementing the CD programme, without any personal instruction, 2 telephone follow-up interviews were carried out after normal exposure to fireworks. Twenty nine owners completed the 8 week training period and the second followup and efficacy was assessed using both owner reports of the dog s natural response and video footage of behaviour during firework exposure pre and post treatment. Results The majority of change occurred during the first month of training and there was a significant improvement (p<0.001) in the mean severity score of all behaviours at the first follow-up, except vigilance. There was no difference between the 2 CD groups in the changes of total severity or global scores from baseline to the first or the second follow-up. Conclusion In this trial, the self-help CD based sound desensitisation programmes, in combination with D.A.P., were reported to help dogs with fear of fireworks, but owner compliance was an issue. After a 60 day treatment period, an average reduction of 60% in the signs exhibited may be expected, depending on the reported signs. However, this trial was not placebo-controlled. * and Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Sound sensitivities

39 Long-term follow up of the efficacy of a behavioural treatment programme for dogs with firework fears. Levine E D, Mills D S Veterinary Record, 2008; 162, Following the earlier trial conducted by Levine E D, et al. (2007), the owners of 38 dogs enrolled in that study were asked to complete follow up questionnaires to assess the efficacy of using noise recordings (Fear of Fireworks and Sound Scary) in conjunction with D.A.P. Diffuser to treat noise phobias. The same questionnaire asked owners to rate both the frequency (0=Never - 3=always) and intensity (1=very low - 5=very high) of each dog s response. These assessments were completed in August 2004 (to give a baseline) and (following treatment) in November 2004, January 2005 and November of the 38 dogs which completed the therapy were exposed to fireworks in November Of these, only 28 completed all 3 questionnaires. The severity of each behaviour was calculated by multiplying frequency by intensity and a total severity fear score was developed for each dog by adding the severity of each behaviour. Results Median total severity score was significantly lower in November 2005 compared to August 2004 (p<0.001) August 04 November 04 January 05 November 05 Mean severity score * * * * * * * * * * * * * * * * * * * * * * * * * * * Run Drool Hide Cower Pace Freeze Vocalise Pant Seek owner Scan Bolt Startle Shake Mean severity scores for individual responses of 23 dogs to noise at baseline (August 2004) and at each follow-up interview following treatment with dog appeasing pheromone and CD-based sound desensitisation therapy. * Significant difference compared with baseline value, P 0.05 Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Sound sensitivities

40 Conclusion In this trial, using a D.A.P. Diffuser alongside desensitisation and an 8-week counterconditioning programme led to significant long-term improvements in the dog s response to fireworks as being reported by owners. It was therefore suggested that this type of programme should be routinely used alongside D.A.P. for the treatment of firework fears in dogs. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Sound sensitivities

41 Dog-appeasing pheromone collars reduce sound-induced fear and anxiety in beagle dogs: a placebo-controlled study Landsberg G. M., Beck A., Lopez A., Deniaud M., Araujo J.A., Milgram N.W. Veterinary Record doi: /vr A blinded placebo-study using a thunderstorm simulation recording was conducted on 24 adult Beagle dogs to assess DAP collar effect in reducing sound-induced anxiety.1,2 The open field test room also included a box for dogs to hide. Thunder test naïve dogs, aged between 7 and 10 years and of both sexes, were allocated into 2 balanced treatment groups (placebo and DAP collar) based on baseline global anxiety scores when exposed to a thunderstorm recording. Each group was then exposed to additional simulation tests on two consecutive days (T1, T2). Each 9-minute simulation included three equal periods; pre (3 min), during (3 min), and following thunder (3 min). Dogs were video-assessed by a trained observer on a 6-point scale for positive (reactive) signs with increased activity including circling, running, digging, climbing, jumping, and barking; for negative (autonomic) signs with decreased activity including freezing, lowered posture, panting, shaking lip licking and yawning, and for global anxiety (combined positive and negative).3 Each anxiety score was analyzed using a three-way ANCOVA with test (Baseline, T1, T2), treatment, and time ( during and following ) serving as main independent variables, and prethunder serving as a covariate. Time spent in hide box was also recorded. Results All anxiety scores were higher during compared to following thunder (p<.0001), but both were consistently higher than pre thunder, confirming the model s validity. Change in anxiety scores during thunderstorm to before 2.5 DAP 2 p = p = ,596 PLACEBO Anxiety score difference p = ,220 2,986 0 Negative anxiety Positive anxiety Global anxiety * Anxiety before corresponds to the value before each thunder Note: LS-MEANS and p-values are issueds from a generalized mixed model for repeated measurements, including treatment effect and test effect as fixed factors and the corresponding baseline measurement Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Veterinary Practice Use

42 Both global and positive / reactive anxiety scores were significantly improved across during and following times compared to placebo at T1 (p=.001 for both) and T2 (p=.007 for global; p=.022 for positive / reactive). DAP significantly decreased global anxiety across during and following thunder times compared to baseline at T1 (p=.006) and T2 (p<.0001). There was no significant improvement in the placebo group over baseline at T1 and T2. In addition in the DAP group, significantly more dogs used the hide box compared to placebo dogs, for both T1 and T2, whatever the time (before: Odd ratio=32.4 [95%CI: ], p= ; during: OR=16.6 [ ], p= and following thunder: OR=10.0 [ ], p=0.0187). The increased hide use is consistent with the improvement in positive anxiety signs in the DAP group, and can be seen as an adaptive response in these dogs Number of dogs using the hide box By test, all times (before, during, following) 1.94 p = p = Baseline Test 1 Test 2 DAP PLACEBO Conclusion DAP collars reduced both global and positive / reactive anxiety to a thunder recording, while increasing the hide use, possibly by counterbalancing noise-related increased reactivity. This supports the use of DAP for reducing noise-related fear and anxiety in dogs. 1. Dreschel, N.A., and Granger, D.A Appl Anim Behav Sci 95, Araujo, J.A., de Rivera, C., Landsberg, G.M., et al J Vet Behav in press, DOI: /j.jveb Levine, E.D., Ramos, D., Mills, D,S Appl Anim Behav Sci 105, Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Veterinary Practice Use

43 Summary and Recommendations for Use Preventing sound fears and phobias Noise phobias can develop as a result of cumulative effect of experience over the dog s lifetime or due to one extreme event. The best way to prevent phobias developing is to ensure puppies are correctly socialised and habituated, to ensure they are able to cope appropriately with loud noises from a young age. CD based or downloadable programs - such as Sounds Sociable (www. soundtherapy4pets.com) can be invaluable and allow the habituation process to start prior to vaccination. Adaptil may also be useful in helping ensure puppies are not overwhelmed during this process, helping reduce the chance of a dog developing problems in later life and support learning. For more information please read the chapter on puppy socialisation. Providing a den or hiding place and habituating the dog to use it as a safe place to be in, is recommended as a preventative measure. Adaptil can be used via the spray onto a cushion or blanket to increase the dog s sense of safety. However, even correctly socialised dogs can still experience worry or fear in response to firework exposure or other sounds like thunderstorms and care should still be taken to limit distress (see recommendations above). Adaptil support may help reduce the intensity of this fear and help prevent mild worries developing into a phobia. Short term management of firework and thunderstorms fears Prepare a den for the dog before the expected event so they have a safe area to retreat to when the worrying noise begins. This can be in an area the dog already choses to use, but is ideally away from windows and doors and in an internal room. By giving the dog meals, treats, chews and toys in the den in the weeks running up to an expected loud noise event (firework night for example), the dog will associate this place as being a safe, relaxing area. This sense of security can be further enhanced by moving the dog s bed inside the den and installing an Adaptil Diffuser nearby. Then the den must be available to the dog at all times, especially when it is alone. Adaptil can also be used via the spray onto a cushion or blanket to increase the dog s sense of safety. The longer the dog is exposed to the pheromone prior to the fireworks or thunderstorms, the better prepared he will be to cope with the challenge as the pheromone will help him with this rising anxiety. Owners should ensure that pets are safely inside and that doors, windows and dog flaps are secured. It is advisable to microchip pets, as if they do escape, they can easily get lost as they are confused or distracted by the noises. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Sound sensitivities

44 Dogs should be taken for walks when exposure to fireworks is less likely, such as before nightfall. This change in routine can be started in the weeks before the anticipated event, so that the dog doesn t use the change of walks as a clue to the impending fireworks. Owners may play music and/or have the TV on to help mask the noise. Fearful behaviours should be ignored. Trying to soothe a fearful dog not only rewards the behaviour, but also gives the impression that the person is also worried about the fireworks. Seeing the owner act in this way further undermines the dog s confidence. Never punish or get cross with a fearful dog, because this will simply make the dog more afraid. If ignoring them is too difficult, playing a game with them can be used as a distraction. Short term medication 1 (benzodiazepines, ideally given 1 hour prior to the noise event) can be used to alter a dog s emotional response and memory of a frightening event. This can make the dog more manageable on the night and prevent the problem from getting worse. Adaptil pheromones products (diffuser, collar, spray) have no known adverse effects and may be safely combined with benzodiazepines. The diffuser is most useful for reducing fearfulness in dogs that are inside during a noise event. Adaptil collar can also be used as an alternative to the diffuser. Adaptil Stress Relief Now Tablets (a nutraceutical combination of natural ingredients) can be used to help the dog remain calm during the event. Just administer 2 hours before the anticipated noise event. They can be used in conjunction with Adaptil Diffuser, Collar and Spray. In case of co-administration with benzodiazepines, doses should be decreased as excessive sedation might be observed. Note that other short-term medications, such as acepromazine, should never be used in noise phobias. Acepromazine is believed to cause heightened sound sensitivity and, by reducing the dog s ability to adopt normal coping strategies, increase fear and make phobias worse 1. For more information visit Long term management of noise phobias CD based programs can be very effective in the long-term treatment of noise phobias. However, poorly managed or inappropriate therapy may make the problem worse. Veterinary professionals are encouraged to only recommend programs supported by peer-reviewed trial data, such as the Sounds Scary program ( or to refer clients to an approved Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Sound sensitivities

45 animal behaviour specialist. Before starting behavioural therapy, it is important to ensure that the dog is healthy and has no cognitive impairment. Behavioural therapy should only be carried out when the chance of exposure to loud noises is small. It typically takes around 6 weeks to begin to produce an improvement, and should therefore be started well ahead of the firework or thunderstorm season or immediately after it. In all cases, desensitisation must be followed by counter-conditioning in order to consolidate any behavioural improvement. Long-term drug therapy* (selective serotonin reuptake inhibitors, tricyclic antidepressants and monoamine oxidase inhibitors) can be considered as useful adjunct to behavioural therapy, when used appropriately and on sufficient time duration. Selegiline (Selgian, Ceva Santé Animale) is a MAOi-B licensed preparation for the treatment of phobia problems in dogs. This drug reduces fearfulness, increases exploratory behaviour and has positive effects on cognition even in healthy animals. It takes 4 to 8 weeks to begin to become effective, and is a useful adjunct to behavioural therapy 1. Adaptil Diffuser, Collar or Spray may help in conjunction with other treatment modalities (in particular during the first weeks of treatment, since most medications may take several weeks to achieve therapeutic effects, and behaviour therapy also takes time). It has been shown to be effective in assisting the response to behavioural therapy, by reducing the dog s general level of anxiety and providing a reassuring environment. Conversely Adaptil Stress Relief Now Tablets should not be administered to dogs treated with SSRIs, TCA and MAOi-B, as it might induce a serotonin syndrom. * Please consult the current data sheet of the relevant drug for full information, including warnings and dosing. 1 British Small Animal Veterinary Association (BSAVA) Policy Statement on the management and treatment of firework phobias in dogs. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Sound sensitivities

46 Veterinary Practice Use Fear and anxiety among dogs visiting the veterinary clinic and the associated problems this may cause is a well recognised and potentially significant welfare problem 1. In a study by Doring et al (2009), 78.5% (106/135) of dogs entering a veterinary clinic appeared fearful, with 61.5% (83/135) visibly trembling 2. This trial also found that age, gender and previous experience were significantly associated with this fearful behaviour 2, with male dogs considered to be less fearful than female dogs. Animals under 2 years of age were also significantly less fearful compared to older dogs. Preferred Supplement Veterinary practices often remind dogs of previous negative experiences which, in conjunction with the restraint used during clinical examination, pain the dog may be suffering and the perceived inability to escape, may trigger an aggressive response. Being able to identify the signs of stress and to take every step to reduce fear should be a primary aim of every animal health professional coming into contact with dogs. Alternative Veterinary Practice Use 1 Landsberg G, Hunthausen W, Ackerman L, Handbook of Behaviour Problems of the Dog and Cat, Saunders, Edinburgh Doring D, Roscher A, Scheipl F, Kuchenhoff H, Erhard M H, Fear-related behaviour of dogs in veterinary practice, The Veterinary Journal, 2009; 182, 38-43

47 A triple-blind placebo-controlled investigation into the assessment of the effect of dog appeasing pheromone (D.A.P. ) on anxiety related behaviour of problem dogs in the veterinary clinic. Mills D S, Ramos D, Gandia Estelles M, Hargrave C Applied Animal Behaviour Science, 2006; 98, The behaviour and emotional state of 15 dogs, known to be fearful of the veterinary clinic, was evaluated in the waiting room and during a sham clinical examination by taking video recordings (5 minutes and 2 minutes respectively), in the presence of either a D.A.P. Diffuser or a placebo placed one week before any assessment. Each dog acted as its own control, by visiting the clinic on two occasions (once with the verum, once with the placebo). The dogs were semi-randomly allocated into treatment groups to control order effects. Two naive independent raters analysed the video recordings to assess the behaviour and ensure the trial was triple-blinded. Results In the waiting room there were no significant differences in the specific categories of recorded behaviour in the two groups. However, there were significant differences in the duration (p=0.045) of the anxious state and both the frequency (p=0.003) and duration (p=0.002) of the relaxed state, with the dogs appearing more relaxed and less anxious when D.A.P. was used. Importantly though, dogs reacted in a normal way when disturbed and showed normal response to activity in the local environment. There were no significant differences in the specific recorded behaviour of the dogs during the 2 minute exploration of the consulting room, but there were significant differences in the duration of the anxious state (p=0.024) and frequency of expression of the relaxed state (p=0.009) with the duration being shorter in the D.A.P. group despite an identical clinical exam being performed in both groups. Seconds Duration of different behaviours in the reception area D.A.P. Diffuser Placebo 0 Investigative Relaxed d Aroused Anxious s Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Veterinary Practice Use

48 Duration of different behaviours in the examination room D.A.P. Diffuser Placebo Seconds Relaxed Aroused Anxious Near Owner r e Investigative Conclusion In this trial, the dogs exposed to a D.A.P. Diffuser at the vet clinic showed reduced anxiety and increased relaxation in both the waiting room and the consulting room. However, there is no evidence that, on a single exposure, it reduces overt expressions of aggression during the clinical examination of dogs predisposed to this behaviour. Further long-term studies are warranted to find out if repeat exposure to fearful situations, such as visiting the veterinary clinic, has a cumulative effect on anxiety. A continuous use of pheromonatherapy in the veterinary environment might help reduce the risks posed by distressed animals at the clinic. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Veterinary Practice Use

49 Recommendations for Use: Routine consultations Adaptil Diffuser is the most convenient formulation to be used in waiting areas and consultation rooms to help comfort and reassure nervous patients. In presence of air conditioning plug in the diffuser away from the air-conditioner, vents, cold air returns, or exhaust fan. If a dog has a history of showing signs of fear during routine consultations, the owner may be provided with an Adaptil Spray or Adaptil Collar for use before bringing the dog into the veterinary practice. However, if a dog has a history of aggression, muzzling is still recommended. Hospitalisation Adaptil Diffuser is the most convenient formulation to be used in the veterinary clinic. Adaptil Spray may be used as required in the kennel (on the dog s bedding), as an additional measure lasting 4-5 hours and requiring to be sprayed 15 minutes before introduction of the dog in the kennel. As an alternative, an Adaptil Collar may be fitted by the owner prior to hospitalisation. Reports suggest that if the dog is already highly aroused then the effects will be more limited, so it is advisable not to wait until the animal shows signs of stress. In addition to the use of Adaptil (Diffuser and/or Spray or Collar), loud noises and excessive numbers of people coming and going should be avoided. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Veterinary Practice Use

50 Car Travel Behavioural problems during car transport are often signs of motion sickness or fear of travel-related stimulus. Signs can include barking, howling, moving from side to side, shaking, vomiting, salivating and urinating. Desensitisation is the key to car training and should begin with a dog learning to sit in a stationary car. The next step is to encourage the dog to get into the car with the engine running, followed by a short trip with subsequent trips getting progressively longer. Preferred Alternative The following trials show how Adaptil (spray or collar) can help support dogs during transportation. However, in serious cases or if the problem is well established, behavioural therapy may also be required. Car Travel

51 Effects of a synthetic dog appeasing pheromone (D.A.P. ) on behaviour problems during transport. Gaultier E, Pageat P Proceedings of the 4th International Behaviour Meeting, Caloundra, Australia, 2003; Thirty two dogs of various breeds, age (between 3 months and 7 years) and sex were included. 15 were allocated to the D.A.P. Spray group and 17 to the control. The trial was double-blind and randomised. The D.A.P. Spray or a placebo spray was applied at least 10 minutes before the dog entered the car. Owners were asked to do at least 4 trips with their dog while a fifth trip was optional. 21 owners made the optional trip, 10 from the D.A.P. group and 11 from the control group. Owners had to indicate which of 11 signs their dog usually exhibited during travel and, after each trip, to evaluate for each sign if it was worse, not changed, improved or disappeared. A car sickness rate was then generated. Results There was a reduction in car sickness in both groups, but the reduction was significantly greater (P<0.01) in the D.A.P. group with each trip, except for the third. D.A.P. had more effect on somatic signs such as salivation, vomiting, urination and defecation than on behavioural signs such as barking and motor activity. Worsened 100% Stable Improved 80% Disappeared 60% D.A.P. Placebo 40% 20% 0% Shaking Pantingng Vomitingng Salivating Restlessness Shaking Panting Vomiting Salivating Restlessness Owners perception of the change in their dogs behaviour after the 4 controlled trips Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Car Travel

52 Improvement * D.A.P. (n=15) * Control (n=17) ** Trip 1 Trip 2 Trip 3 Trip 4 Owners perception of the overall change in their dogs behaviour per trip * p<0.05 ** p<0.01 Conclusion In this trial, D.A.P. Spray was shown to have a positive effect in relieving the apprehension of dogs during car trips thus helping manage signs of car sickness. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Car Travel

53 Signs of travel-related problems in dogs and their response to treatment with dog-appeasing pheromone (D.A.P. ). Gandia Estelles M, Mills D S Veterinary Record, 2006; 159, Sixty two dogs with problems travelling in the car took part in a non-blinded study using D.A.P. Collars for 6 weeks. The dogs were taken out in their owner s car at least twice weekly over a period of 9 weeks. Each dog s behaviour was assessed at week 0 (baseline), 1, 2, 3, 4, 6 and 9 (following removal of the collar at week 6). A further follow-up assessment was then made between 3 and 5 months after the removal of the collar. 21 signs of distress were identified and on the basis of these signs the dogs were divided into 5 groups excitable, nausea, tense, attentionseeking and elimination. The attention-seeking and elimination groups were combined when assessing the effect of the treatment for statistical analysis. Three dogs were withdrawn from the study and only 55 of the remaining 59 owners answered the follow-up questionnaire. The average age of the 59 dogs was 5 years (6 months to 12 years). This trial featured 14 entire and 29 neutered males and 5 entire and 11 spayed females and included a mixture of pure and cross breed dogs. Results All the groups showed statistically significant improvement after treatment, but their responses were not uniform. The greatest perceived improvement was among the nausea group and the least was among the excitable group. In the groups that had sufficient data for analysis, there was no evidence of a relapse in most of the signs 3 weeks after the removal of the collar, or at the follow-up after 3 to 5 months: the improvement was still significant. Conclusion The D.A.P. Collar may be effective in helping to control signs relating to car travel in dogs. Further trials with a similar design, but including placebo-control are required to confirm the efficacy of D.A.P. in such circumstances. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Car Travel

54 Recommendations for Use: Helping dogs cope with car travel Get the dog used to being in the car for short periods without going anywhere. Associate the car with treats and play. Initially go for short rides and then progressively increase the distance and speed. Ideally, the dog should have eaten nothing for at least 6 hours prior to travel to avoid nausea and vomiting, but do not limit water before travelling. Apply Adaptil Spray to the dog basket, bedding or cage approximately 15 minutes before travelling. Re-apply on toilet and exercise breaks, every 4-5 hours as necessary. On long journeys an Adaptil Collar may be a more convenient formulation. N.B. Adaptil has also been reported to aid dogs travelling by air. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Car Travel

55 What is Feliway When a cat feels safe and secure, it rubs its head against objects in the local environment, leaving behind substances called facial pheromones. These provide emotional support and help regulate feline stress. The absence of these familiar marks is believed to lead to an increase in anxiety. Feliway is a synthetic copy of the F3 fraction of the facial pheromone proven to reassure and comfort the cat. Cats only need to detect a small amount of the pheromone for it to elicit the desired response. Due to their unique mode of perception and action, it is impossible for cats to overdose, become immune or adversely react to pheromones in any way. What is Feliway Feliway is non-sedative, non-systemic and as such has no contraindications. Pheromones are species-specific. It is thereby impossible for Feliway to affect humans or other pets. The effect of Feliway has been shown in more than studies published in reputable scientic scientific journals or or at international conferences. (at the end of 2010). Feliway is available as a diuser or as a spray, but not as a collar. Feline Feliway experts warn is available that tting as a a diffuser territorial as pheromone a spray, but collar not as to a collar. a cat Feline is not experts relevant warn on an that ethological fitting a point territorial of view, pheromone because a collar cat expects to a cat to is find not relevant the F3 fraction an in ethological its environment point of and view, not because on itself. a It cat might expects create to some find the disorientation. F3 fraction in Moreover, its environment promoting and a not feeling on itself. of safety It might in create unfriendly some disorientation. environments (street, Moreover, neighbourhood promoting pets, a feeling etc.) is of unsuitable. safety in unfriendly environments (street, neighbourhood pets, etc.) is unsuitable.

56 There is a Feliway solution to every situation PRODUCT USES FELIWAY DIFFUSER FELIWAY SPRAY 60ML/20ML RECOMMENDED duration of use Urine Spraying + Minimum 1 month Vertical Scratching + Daily for minimum 1 month Multi-Cat Household Continuously Changes to Cats Environment - New arrivals (baby, pets, etc) - Redecorating, new furniture - New home + Begin use at least 24 hours prior to changes and use for minimum 1 month Stressful events - Holidays - Parties - Fireworks - Thunderstorms + Begin use at least 24 hours prior to events and use during a week after Travel Vet visits 15 min before putting the cat into the sprayed carrier. Re-apply every 4-5 hours Cattery + Daily. Apply spray without the cat in the area = Product most suited for the situation + = Additional Feliway products to combine for added support All cats are unique and results may vary. You may see improvements in as little as a week. For best results, use continuously for 30 days. Feliway is not recommended for excessive vocalizations or inappropriate elimination (outside the litter box) that is not urine spraying. Please consult your veterinarian to rule out potential medical issues. Feliway is not recommended for overt aggression between cats or towards owners. Additional behavioural and environmental modifications may be required and advice should be sought from your veterinary practice.

57 Feline Urine Marking Urine marking, characterised by the deposition of small amounts of urine on vertical surfaces, is one of the most common 1 feline behaviour problems, with indoor spraying displayed by more than 20% of domestic cats 2. There are 2 types of feline urine spraying, sexual and reactional or stress-related. Sexual marking is associated with sexual excitement in male cats or the onset of oestrus in female cats. Reactional or stress-related marking is associated with a stressful event, a change in the cat s environment or an ongoing stressful situation, such as felines sharing space in multi-cat households. Preferred Supplement Urine or scratch markings are likely to occur in the following situations: Building work Redecoration Moving house Rehoming Boarding in a cattery Hospitalisation Illness Changes to an owner s routine Multi-cat household Loss of a feline companion or owner Introduction of a new pet or person Stressful events Christmas, social gatherings, Bonfire Night Restricted access to territory etc... First recommendation to manage the problem includes neutering, to help solve the sexual marking behaviour. Additional current strategies advocate behavioural modifications to remove any specific triggers and provide environmental enrichment (in particular in multicat households) alongside specific interventions, including pheromones. Feline Urine Marking 1 Beaver B V, Feline Behavioural Problems, Veterinary Clinics of North America, 1976; 6, (3) Hart B L, Hart L A, Canine and feline behavioural therapy. Lea and Febiger, Philadelphia 1985;

58 Functions and use of the facial pheromones in the treatment of urine marking in the cat. Pageat P Proceedings of the XXIst Congress of the World Small Animal Veterinary Association, Jerusalem, Israel, 1996 First study - the effect of applying facial secretions to areas marked by male tomcats in the presence of females. Each of the 15 recruited tomcats lived with females and sprayed at home for more than 3 months. The owners were ask to count the number of urine spots each day for 4 days before the beginning of the treatment. The tomcats faces were brushed with a surgical compress to pick up the facial secretions. The secretions were then applied to the areas marked by the tomcat. The owners were asked to record any change in frequency of urine spraying. Second study - the effect of applying facial secretions to areas marked by male and female cats. The first study was repeated using 84 spraying cats (males and females, neutered and entire). The secretions were again applied to the areas marked by the cats, as well as the corners of furniture, doorways etc. The daily number of urine marks was recorded over 28 days. Third study - the use of the synthetic F3 pheromone on the spraying activity of cats. A third study looked at the use of the synthetic F3 on the spraying activity of 61 cats (29 neutered males, 22 neutered females, 9 females and 1 male) aged from 1 to 6.5 years old. All had begun to urine mark over the previous 1.5 to 3 months. Both areas sprayed by the cats and other prominent objects were treated once a day with synthetic F3 (Feliway ). Treatment was applied for 28 days. The cats were observed for 49 days (to record any incidences of relapse). Results First study - The change in urine spraying was significant. Before the treatment areas were marked with urine approximately 5.2 times per day. During the treatment the areas were only marked 0.6 times per day. Second study - After day 7, urine marking had ceased in 89% of cases. However in following studies up to 20% of owners found the method inconvenient and unsatisfactory. For this reason an artificial analogue of the F3 pheromone was synthesised (Feliway ). Third study - Spraying decreased from 14.8 marks per day to 1.6 marks on day 7. By day 28, 59 cats had stopped marking altogether, with no relapse seen by day 49. This is a success rate of 96.7%. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Feline Urine Marking

59 20 15 Average number of urine marks Average neutered males Average spayed females Average females Entire males Day 0 Day 7 Day 14 Day 21 Day 28 Conclusion Feline facial secretions are antagonists of urine spraying therefore, artificial structural analogues of pheromones (Feliway ) can be used to manage this unacceptable behaviour in cats. The results of these preliminary not placebo-controlled studies have been confirmed by subsequent trials. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Feline Urine Marking

60 Experimental evaluation of the efficacy of a synthetic analogue of cats facial pheromones (Feliway ) in inhibiting urine marking of sexual origin in adult tomcats. Pageat P Journal of Veterinary Pharmacological Therapy 1997; 20, 169 A caged female cat in oestrus was placed in front of another cage containing a cardboard box. Each of the 3 tomcats, known to spray as a result of sexual excitement, were then introduced to the second cage, left on their own for 30 minutes and allowed to spray. A fresh cardboard box was used for each cat. This process was repeated using a cardboard box previously sprayed by a different male cat. Finally, the study was repeated again after treating the sprayed cardboard boxes with Feliway Spray. The number of urinary marks was noted for the first cat, stimulated by the presence of urine from the second cat for 30 minutes and then by the presence of urine from the third cat for a further 30 minute-period. A similar protocol was used with the 2 other males. Results In the presence of a box sprayed by another male, the first cat marked 5 times and the second and third cats marked 7 times. Following the use of Feliway the first cat did not mark the box at all, and the second cat and third cats marked once. Number of marks Average number of urine marks Without Feliway With Feliway 1 0 C1 C1F3 C2 C2F3 C3 C3F3 C1, C2 and C3 = Number of marks without Feliway C1F3, C2F3 and C3F3 = Number of marks with Feliway Conclusion In this trial, Feliway Spray was effective in inhibiting or substantially reducing sexual urine marking in adult tomcats. This study was carried out in demanding circumstances, as the tomcats were encouraged to mark by the presence of the female in oestrus and the marking of other competing tomcats. Despite this the inhibitory effects were apparent very shortly after using Feliway. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Feline Urine Marking

61 Efficacy of synthetic feline facial pheromone (F3) analogue (Feliway ) for the treatment of chronic non-sexual urine spraying by the domestic cat. White J C, Mills D S Proceedings of the First International Conference on Veterinary Behavioural Medicine, Birmingham, 1997; 242 Fifty seven cats ranging in age from 8 months to 17 years were recruited from 46 households of up to 5 cats (neutered males, entire or neutered females). The subjects had been urine spraying for an average of 4.6 years. For the first 7 days of the trial (baseline), the owners were asked to record the number of urine marking instances over each 24-hour period. Feliway was then applied for 5 weeks where the cats had been spray marking and onto other prominent objects. On average, households treated 8-9 areas. Single applications were made in single cat households and twice daily applications in multi-cat households, until the offending cat had been observed rubbing its face on the treated area (depositing facial pheromones). Progress was monitored on a weekly basis. Results On day 35, 52 out of 57 cats (91%) had reduced their frequency of spraying and 30 (57%) had not sprayed after day 28 of the trial. Neither the number of cats in the household, age of cats nor duration of problem were predictive of the degree of improvement obtained. Conclusion In this trial, Feliway Spray was seen to be effective in inhibiting or substantially reducing chronic long-term non-sexual urine marking in domestic cats. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Feline Urine Marking

62 Urine spraying in cats: presence of concurrent disease and effects of a pheromone treatment (Feliway ). Frank D, Erb H N, Houpt K A Applied Animal Behaviour Science, 1999; 61, Thirty four cats were recruited from 24 households, aged from 3.5 to 16.5 years. All had a history of urine spraying of between 5 months and 10 years. Each was given a thorough physical examination at the beginning of the trial, including a CBC, a blood biochemistry panel, urinalysis, urine culture, urine cortisol, creatinine analysis and abdominal radiographs. Nineteen households (22 cats) completed the trial, with 9 of the cats being strictly indoor cats and 10 outdoor cats (up to 60 % of the time). All were multicat households (from 2 to 14 cats, mean 4.5, median 3). Feliway Spray was applied daily to all urine marks and to other prominent locations for a period of 4 weeks. The owners were asked to record the number of urine marking instances over each 24-hour period during the 4 week treatment phase. Owners were then asked to stop applying Feliway for 4 weeks and again recorded the frequency of spraying. Results Diagnostic procedures revealed abnormalities and/or crystalluria in 13 cats (38%). 7 (21%) of these cats had medical conditions involving the urogenital system and 8 (24%) had crystalluria. Spraying frequency decreased in both indoor and outdoor cats by on average 66.5% (median 75%). This concerned 74% of the households. There was no relapse within the 4 weeks post-treatment. A proportion of households with overt inter-cat aggression also reported a decrease in fighting. The 3 households with overt intercat aggression reported no significant change in urine spraying. Conclusion In this trial, Feliway significantly reduced the frequency of spraying behaviour on vertical surfaces. The author also suggests that combination of pheromone treatment with environmental modifications and pharmacological treatment may improve success rates in inhibiting urine spraying. The potential effects of urinary pathologies on spraying behaviour were not examined, but spraying cats had similar prevalences of crystalluria and struvites as the general hospital cat population. This was not a placebo controlled trial. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Feline Urine Marking

63 Evaluating a feline facial pheromone analogue (Feliway ) to control urine spraying. Hunthausen W Veterinary Medicine, 2000; 95, Cats were recruited based on a history of urine spraying and the data from 57 US households was analysed (mean of 3.8 cats per household). Feliway Spray was applied twice daily to vertical urine marked spots and prominent vertical objects at home and owners were asked to record the number of marks which occurred during the week before Feliway use and during a subsequent 4 week treatment period. The cats were aged 4 months to 16 years (mean 6.7 years). All cats had a history of urine spraying ranging from 5 days to 10 years (mean 2.7 years). Of the spraying cats, 39 were males and 11 were females and the sex of 7 cats was unreported. Results The total number of urine marks per week reduced during Feliway use. Significant decreases in the number of marks were identified within 1 week of treatment and this trend continued throughout the 4 week study period. Urine spraying was totally eliminated during the study period in 33% of households. 20 Mean number of urine marks per week Week 0 Week 1 Week 2 Week 3 Week 4 Conclusion In this trial, Feliway appeared to decrease urine spraying in a variety of household settings and population densities. In addition, the number of urine marks per household significantly decreased within one week and continued after each week of product use. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Feline Urine Marking

64 Long-term follow-up of the effect of a pheromone therapy (Feliway ) on feline spraying behaviour. Mills D S, White J C Veterinary Record, 2000; 147, Telephone interviews were conducted with the owners of 43 cats that had been involved in an earlier study by White and Mills (1997) approximately 10 months previously which consisted in spraying Feliway on areas marked with urine, for 5 weeks. Questions asked as part of these interviews included: when they last used the pheromone, how frequently they used it, how often their cat sprayed and, if appropriate, when the cat(s) had resumed spraying. Results Six (14%) cats were still not spraying approximately 10 months after Feliway use. 27 (63%) were spraying at a lower rate than when the trial started, 7 (16%) were spraying at the same rate and 3 (7%) had deteriorated further. 21 owners had not used the treatment in the previous 7 months. 13 were still using the pheromone treatment in the home, but none were continuing to use it on a daily basis. 9 had used it only when the cat sprayed and 4 on an occasional basis between 1 and 3 times a week. 11 owners reported that the urine spraying had increased slightly between 1 and 2 months after they had stopped using Feliway and a further 10 reported a similar change some time later than this. Incidence of cats spraying 10 months after Feliway use 14% Cats not spraying 7% Deteriorated further 16% Spraying at the same rate 63% Cats spraying at a lower rate Conclusion Results suggest that treatment with the F3 analogue (Feliway ) can lead to a longterm change in spraying behaviour by cats. In this study, 77% of cases were still under adequate control 10 months after treatment. According to this open-label trial, Feliway appears to be more effective in both the short and long-term than other physical or behavioural therapies for the control of non-sexual urine spraying in felines and should be considered a first line treatment. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Feline Urine Marking

65 Clinical trial of a feline pheromone analogue (Feliway ) for feline urine marking. Ogata N, Takeuchi Y Journal of Veterinary Medical Science, 2001; 63, Thirty six cats were recruited from 52 veterinary hospitals across Japan. All the cats had a history of urine marking (1 month to 10.5 years - median 13.5 months) and were marking on average 14.2 times per week at inclusion). 28 cats were from multicat households (mean 4.8 cats) and 8 were single cats. The method followed that of Frank et al (1999). The owners were asked to fill out a questionnaire to determine the frequency of urine marking. Results By the end of the first week of treatment with Feliway, urine marking decreased significantly. It dropped to 4.2 times a week at the end of the trial (after 4 week s treatment) and remained the same throughout the 4th week post-treatment observance period. The frequency of marking decreased in cats with or without inter-cat aggression, although it was sustained at a higher level in cats with inter-cat aggression. Effectiveness of treatment Unchanged (>50% pre-treatment) Reduced ( 50% pre-treatment) 40% 23% 37% Totally eliminated Immediately after 4 weeks of use Unchanged (>50% pre-treatment) Reduced ( 50% pre-treatment) 38% 24% 38% Totally eliminated 4 weeks after the cessation of treatment Conclusion In this trial, treatment with Feliway appeared to reduce or eliminate feline marking problems in up to 77% of cases after one month of treatment. In addition, 41.7% of the owners felt that their relationship with their cats improved with the use of Feliway. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Feline Urine Marking

66 Evaluation of a novel method for delivering a synthetic analogue of feline facial pheromone (Feliway ) to control urine spraying by cats. Mills D S, Mills C B Veterinary Record, 2001; 149, Twenty two cats with urine spraying problems were recruited onto a doubleblind placebo study and randomly assigned to 1 of 2 groups. 10 cats received the pheromone via a plug-in diffuser and 12 cats received a placebo (no significant difference in the demographic of the 2 groups). The electric devices had to be placed in the room where the problem was worse, and switched on continuously for 4 consecutive weeks. In the treatment group, 7 cats were male and 3 female (all neutered) and lived in a household with a median number of 2.5 cats (but only one cat was spraying outside the litter box). 1 cat never had access to the outside. The median duration of the problem amongst the treatment group was 24 months. In the placebo group, 8 were male and 4 female (11 neutered, 1 entire queen) and lived in a household with a median number of 1.5 cats (but only one cat was spraying). 2 cats in the group had restricted access outside. The median duration of the problem amongst the placebo group was 21 months. Results A reduction in urine spraying by the fourth week of treatment was recorded in 9 of the 10 cats in the treatment group and 7 of the 12 cats in the placebo group. In the placebo group, 2 cats were spraying with the same frequency at the end of the study and 3 more frequently. However, the difference was significant only in the treated group (p=0.004). By the fourth week of treatment, the mean weekly level of spraying had decreased in both groups: from 11.9 (baseline) to 5.7 (4th week) in the Feliway group and from 9.5 to 8.58 in the placebo group. In addition, the efficacy tended to increase with time. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Feline Urine Marking

67 Mean spraying total for previous 7 days Feliway group Control group Week Change in spraying over time, plots represent mean level of spraying within the group over the previous 7 days (with error bars) as a proportion of the level of spraying in the baseline week. Conclusion In this trial, Feliway was shown to be effective when applied continuously as a vapour via a diffuser for the reduction of urine spraying and the control of new marks. This method is more convenient for owners than daily applications of a spray, and is likely to result in greater compliance and improved success in treatment. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Feline Urine Marking

68 A Meta-Analysis of Studies of Treatments for Feline Urine Spraying. Mills DS, Redgate SE, Landsberg GM PLoS ONE 6(4): e doi: /journal.pone Feline urine spraying at home is a common behaviour problem that owners seek advice for from veterinarians. Current strategies advocate cleaning urine marks and behavioural modifications to remove specific triggers alongside psychopharmacological and non pharmacological interventions such as use of the feline facial pheromone in the environment. Several trials relating to different treatments are available in the literature, but without any consensus to date on the value of each treatment compared to the others. It appears that none is successful in completely resolving the behaviour in all spraying cats. This current study aimed to meta-analyse data from published trials that evaluated treatments for feline urine spraying. The search, done in 2009 on three electronic databases, included the following terms: Urine spraying, Urine marking, Cat, Feline, Behaviour/Behavior. Included studies had to be published as a peer reviewed publication, to provide sufficient information to extract representative data, and only to be about reactional vertical spraying. Among 24 identified studies, only 10 (from 9 publications) were suitable for analysis: 4 evaluated pheromonatherapy (the use of Feliway, a synthetic analogue of the F3 facial fraction in the cat) and 6 pharmacotherapy papers (clomipramine or fluoxetine). Since all studies were not placebo-controlled, a placebo effect was calculated from two randomized controlled studies, then used in subsequent comparisons. Studied cats were mostly indoor, and living as single or multi-cats. A first analysis compared pheromonotherapy and pharmacotherapy in terms of the number of cats that ceased or reduced spraying by at least 90% (meaning a decrease in spraying between 90 and 100%). A second analysis focused on pheromone papers, with the number of cats that reduced spraying from baseline levels (whatever the decrease, compared to initial spraying). Results The authors found a significant (p=0.001) association between the use of any intervention (Feliway or psychoactive drugs) and the number of cats that stopped or reduced spraying by at least 90%. Analysis by intervention type indicated that fluoxetine, clomipramine and pheromones may each assist in managing urine spraying beyond a placebo. Pheromone trials showed a more limited effect (not significant) in the number of cats that ceased or reduced spraying by at least 90%, compared to drug treatments, but in favour of Feliway compared to a placebo. However, the comparison was done whatever the treatment duration (due to initial individual study designs), although fluoxetine and clomipramine trials lasted much longer than pheromone trials (respectively up to 16 weeks compared to only 4 weeks). Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Feline Urine Marking

69 In addition, some environmental modifications were implemented alongside drug treatment, whereas no change was added to pheromone use. Thus, pheromone effect reported here may be underestimated. When looking at any reduction in spraying behaviour, a significant effect (p=0.05) was evidenced after 4 weeks of Feliway use, compared to initial spraying rate. Conclusion This provides the strongest evidence to date that both psychoactive drugs and pheromonotherapy are of added value in the management of feline spraying. This paper also highlights the need of further blinded controlled studies lasting for at least 8 weeks assessing the cessation or decrease of spraying at least 90%. Those would allow more direct comparison between the efficacy of synthetic pheromones and drugs, as well as compliance (daily oral dossing for drugs versus plugging-in a diffuser monthly). Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Feline Urine Marking

70 Recommendations for Use: Reduce or prevent urine marking Do not clean marked areas with products that contain ammonia or bleach as cats are extremely sensitive to strong smells. Water, surgical alcohol or an odourless solution should be used to treat the soiled areas. Then allow to dry naturally. A Feliway Diffuser should be plugged in the room where the marking has taken place or the room most frequented by the cat. Diffusers should not be plugged in under furniture, as circulation of Feliway will be impaired and the efficacy of the product may be affected. The diffuser should be switched on continuously for at least 4 weeks and the refill replaced as required. Treatment should be stopped when the cat marks the area with its own facial pheromone (is seen to rub the site with its head). Where this is not observed, continue for at least 1 month. This method is more convenient for owners than daily applications of a spray and it is believed to help increase owner compliance 1. However, if the cat marks several rooms, the additional use of a Feliway Spray may be necessary, necessary. or the addition of another diffuser. In such cases, the marked area should be cleaned and allowed to dry. Then Feliway Spray applied daily to both the site and nearby prominent objects. The product will not stain or mark. Nevertheless, it is advisable to test the product on a sample that is not easily visible prior to using it. If a cat has a history of urine spraying, the Feliway diffuser should be plugged into the room where the cat spends most of its time at least 48 hours before any stressful event, such as the arrival of a new pet, building work, Christmas, moving house etc. Alternatively, if a new object is being introduced to the home, i.e a new sofa, Feliway Spray should be applied directly onto the object if safe to do so. Feliway should never be sprayed near an open flame. In addition to pheromonatherapy, behavioural and environmental modifications may be required, particularly in multicat households. See also the AAFP/ISFM Guidelines (and the related handout) on House-Soiling Behavior in cats and the ones on Feline Environmental Needs. 1 Mills D S, Mills C B, Evaluation of a novel method for delivering a synthetic analogue of feline facial 1 pheromone Mills D S, Mills to control C B, Evaluation urine spraying of a novel by cats, method Veterinary for Record, delivering 2001; a synthetic 149, analogue of feline facial pheromone to control urine spraying by cats, Veterinary Record, 2001; 149, Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Feline Urine Marking

71 Travel and New Environments e.g. moving house, holidays, travel, catteries and rehoming When a cat feels safe in its environment it rubs its head from the side of its chin to the base of its ear, depositing facial pheromones on household items such as furniture. These marks reassure the cat and help it feel more secure. In new surroundings it may feel lost and uneasy, which can cause the cat stress and exacerbate or lead to a range of stress related behavioural and medical problems. Going into a cattery, moving to a new house/home, travelling by car or even just a few changes at home (new furniture, redecoration, etc..) can be particularly stressful for a cat. Here there are no reassuring marks and a plethora of strange noises, smells and often other cats to cope with. Preferred Supplement Preferred and Supplement according to the use table Feliway Spray and Feliway Diffuser can help in those situations, as is shown by the trials outlined in the following chapter. Travel & New Environments

72 Usefulness of the F3 synthetic pheromone, Feliway, in preventing behaviour problems in cats during holidays. Pageat P, Tessier Y Proceedings of the First International Conference on Veterinary Behavioural Medicine, Birmingham, 1997; 231 Sixty eight cats of 8 months of age and over, with no particular behavioural problem, were divided into 2 parallel groups (Feliway Spray or placebo). Each travelled with their owners to a holiday cottage at least 60 miles (about 100 km) away from home, where they remained for 10 days or more. Each owner was asked to spray prominent objects within the home with the product provided (Feliway Spray or placebo). Owners were asked to ensure their cat s last meal before the trip was eaten the night before and they left for the cottage early the next morning. The study used 3 behavioural parameters: feeding behaviour (owners were asked to offer a meal to the cat on arrival and record any delay in eating), urine marking (owners were asked to record any incidence of spray marking and count the number of occurrences) and escaping (owners were asked to record whether their cats spent one or more nights away from the holiday home during their stay). Results No spraying occurred in the Feliway Spray group and the cats were seen to eat 35 minutes (+/- 7.5) after arriving in the new environment. 23.5% of the cats in the control group were observed to urine spray and it took 170 minutes (+/-3.8) (2 hours 50 minutes) before the control cats would eat. In addition, all the cats in the Feliway group returned to the holiday home every night, while 61.8% of the control group didn t return after their daily walks, requiring to be supervised or shut in. Statistical analysis showed that the results for all 3 criteria were statistically significant (p 0.05). Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Travel and New Environments

73 Time in minutes Feliway Placebo Time taken for cats to eat in a new environment. P % of cats Feliway Placebo Feliway Placebo Spraying Cats spending one or more nights outside % of cats urine spraying or retreating outside following introduction to a new environment. P Conclusion This trial suggests that Feliway is a useful tool in helping cats settle into a new environment and preventing the potential stress-related problems such as urine spraying or running away. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Travel and New Environments

74 Effect of a feline facial pheromone analogue (Feliway ) on manifestations of stress in cats during transport. Gaultier E, Pageat P, Tessier Y Proceedings of the 32nd Congress of the International Society for Applied Ethology, Clermont- Ferrand, France, 1998; 198 Fifty eight adult cats, ranging in age from 1 to 7 years, were assigned to 1 of 2 treatment groups (Feliway Spray or placebo). Each cat was put in a carrier and driven by car between 60 and 300 miles (100 and 480 km). Treatment consisted of 8 spray applications of the product provided (Feliway Spray or placebo) to the cat carrier half an hour before departure. The trial was blind therefore the owners were not aware of the solution they were applying. Incidences of quantifiable stress-related behaviour (somatic responses) such as vomiting, urination or defecation were recorded. Non-quantitative undesirable behaviour such as meowing, agitation and salivation were scored by owners using a stress scale, graduated from 0 (quiet trip) to 6 (the driver had to stop the car). This information was then combined to give a global score. Results Comparison of these scores showed a significant discrepancy in favour of the test group (p<0.001). Global Stress Score Feliway Placebo Overall global score calculated from indications of stress shown by cats in Feliway and placebo groups. P< Conclusion In this trial, Feliway Spray showed a high efficacy in reducing somatic stress responses and anxiety-related behaviours in cats during car travel. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Travel and New Environments

75 Recommendations for Use: Help cats cope with car travel Apply Feliway Spray to the cat carrier approximately 15 minutes before introducing the cat. 1 spray should be administered to each of the 4 corners, 2 sprays to the floor and 2 sprays to the top of the carrier, to allow the alcohol to evaporate. Ideally, the cat should have eaten nothing for at least 6 hours, to avoid nausea and vomiting but don t limit water intake before travelling. Re-apply Feliway before each journey, after thorough cleaning of the carrier. See also the AAFP and ISFM Client Handout: Getting Your Cat to the Veterinarian. Reducing the Stress of Veterinary Visits for You and Your Cats. Help cats cope with a stay in a cattery Empty cabins should be sprayed with Feliway first thing in the morning at least 15 minutes before the cat is likely to be introduced. 1 spray should be administered to each of the 4 corners of the raised indoor section/cabin and 2 sprays to the floor and 2 to the ceiling. Feliway Spray can also be applied to the upright sections of the outside pen at cat height. Cabins can be re-sprayed following daily cleaning. However, if cats are fearful and do not want to leave the cabin, new bedding may be sprayed (again left for the necessary time) before being introduced into the cabin to replace old. N.B. Always take care to ensure at least some old familiar bedding is left with the cat to give added reassurance. Allow time for any fumes from the cleaning products to disperse as much as possible, and for the pens to dry. Feliway Diffusers can be used in indoor runs if a socket is available. In addition to Feliway, avoid loud noises in the cattery and people excessively coming and going. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Travel and New Environments

76 Helping cats settle in other unfamiliar environments, e.g. holiday home, moving house, redecoration, visiting friends The cat should be released into a quiet room where there are plenty of places to hide while it adjusts. Plug a Feliway Diffuser in the room where the cat is released (ideally at least 24h before introducing the cat). The Diffuser should be plugged in continuously until problems subside. Diffusers should not be plugged in under furniture, as circulation of the pheromone will be impaired and the efficacy of the product may be affected. In some situations (for example rearrangement of the furniture), Feliway Spray can be used in conjunction with the Diffuser. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Travel and New Environments

77 Veterinary Practice Use Going to the veterinary clinic and/or being hospitalised involves a dramatic and sudden change to a cat s environment and can be highly stressful. In the practice, cats are shut in cages, handled by unfamiliar people and forced to alter their eating patterns 1. In such circumstances cats usually spend more time being vigilant and attempting to hide than resting for recovery, eating or even behaving normally. In fact, not only are many conditions caused or exacerbated by stress, but stress is also known to have a negative impact on recovery. As a result, any attempt to reduce feline stress in a veterinary environment, including the use of Feliway in the hospitalisation room, as well as in the waiting and the consultation rooms, is recommended. Preferred Supplement Veterinary Practice Use 1 Carlstead K, Brown J L, Strawn W, Behavioural and physiological correlates of stress in laboratory cats, Applied Animal Behaviour Science, 1993; 38,

78 Effects of a synthetic facial pheromone (Feliway ) on behaviour of cats. Griffith C A, Steigerwald E S, Buffington C A Journal of the American Veterinary Medical Association, 2000; 217, The cats in this study were at least 1 year of age and of a variety of breeds. Each was admitted to the veterinary hospital and housed individually in a cage, which included a litter tray, food bowl, water bowl and clean towel. Cats were kept in a typical ward that housed other cats and dogs and were therefore exposed to the typical noises, odours, sights and disturbances expected in the ward environment. First study - Twenty cats (more than 1 year-old, varied breeds, 13 of which being admitted for evaluation of signs of lower urinary tract disease) were assigned to two groups (treatment group -4 healthy, 6 ill cats- or control group -3 healthy, 7 ill cats-). Each cat was placed in a cage containing a small cotton towel that had been sprayed 30 minutes previously, with either Feliway or the control solution. The cats were then videotaped for 2 hours 5 minutes to record the occurrence of various behaviours. Food intake was also measured. Second study - Twenty cats were assigned to 2 groups. All cats were exposed to the feline facial pheromone (Feliway ), a cat carrier was also placed in the group 1 (2 healthy, 8 ill cats) cages but not in the group 2 (5 healthy, 5 ill cats) cages. Ill cats showed signs of endocrine, gastrointestinal, lower urinary tract or renal diseases. 24- hour food intake was measured. In all other ways, the protocol was the same as the first study (video-recording for behaviour analysis). Results In the first study, significant increases in grooming and interest in food were found in cats exposed to the feline facial pheromone compared with the control. In the second study, 24-hour food intake was significantly higher in cats exposed to the pheromone and the cat carrier, compared with cats exposed to the pheromone alone. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Veterinary Practice Use

79 16 * Feliway Placebo Number of episodes in 125 minutes * * * 0 Grooming Interest in food First study (in cages) * p<0.05 Number of cats eating Feliway and cat carrier Feliway alone * * 0 24 hour food intake Second study (in cages with a cat carrier) * p<0.05 Conclusion In this trial, exposure to Feliway increased normal grooming, interest in food and food intake (increased by the addition of a cat s carrier in the cage) in hospitalised cats. Results suggest that exposure to Feliway may help cats feel more at ease in cage, in addition to the benefit of other features of the environment provided in the cage. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Veterinary Practice Use

80 A synthetic fraction of feline facial pheromones (Feliway ) calms but does not reduce struggling in cats before venous catheterisation. Kronen P W, Ludders J W, Erb H N et al Veterinary Anaesthesia and Analgesia, 2006; 33, Seventy seven healthy cats were presented for elective surgery. All cats were given glycopyrrolate and oxymorphone (by SC route) and assigned to 1 of 4 treatments (acepromazine and Feliway, acepromazine and placebo, Feliway only and placebo only). Acepromazine was given at 0.04 mg/kg SC and Feliway was sprayed onto cage paper before the cats were introduced. The behaviour of the cats was recorded on videotape and given, for evaluation, to assessors unaware of treatment group. A catheter was then introduced into the vein of each cat by veterinary students that were unaware of the treatment groups. Based on each cat s response to catheterisation (struggling efforts or not), the students decided whether intramuscular ketamine (5 mg/kg) was required. Results Cats in the acepromazine and Feliway group appeared to be calmer than the acepromazine and placebo cats on the basis of head position and their location in the cage (suggesting benefit from feline facial pheromone among cats receiving acepromazine) but appeared to be less sedated. Cats in the acepromazine and pheromone group also appeared to be calmer than those in the pheromone group based on head position and location in the cage. Cats in the pheromone group were calmer than those in the placebo group based on their body and leg position. Exposure to the pheromone did not significantly reduce struggling at catheterisation. Nevertheless, the students were able to catheterise all cats. Conclusion There were no detrimental behavioural effects associated with either feline facial pheromone or acepromazine. The pheromone had additional calming effects in cats given acepromazine and, to a lesser degree, helped calm cats that were not given acepromazine. This trial suggests that Feliway helps to calm cats in unfamiliar surroundings during hospitalisation. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Veterinary Practice Use

81 Improving the feline veterinary consultation: the usefulness of Feliway spray in reducing cats stress. Pereira J.S., Fragoso S., Lavigne S., Beck A., Varejão A.S., da Graça Pereira G. Journal of Feline Medicine and Surgery, 2015; July DOI: / X Going to the veterinary clinic is a stressful experience for most cats. This study aimed to investigate how Feliway Spray might help reduce cats stress and ease their handling, when used in consultation. A randomized, double-blind, placebo-controlled clinical trial was made, using a sample of 87 cats of both sexes, aged between 7 months and 15 years and whose health on consultation showed no signs of disease. A Feliway spray and a placebo solution spray were tested in two consultation rooms. During the first phase, Feliway spray was applied in the examination table of one room and the placebo spray in the other. After a washout period of 15 days the sprays allocation was switched. During the first 15 minutes of general examination by the veterinarian, the stress and behavior of the cats were assessed by the observer based on a 7-level Cat-Stress-Score and a 5-point Scale of Handling. Difference to usual behavior was also asked to the owners. Cats exposed to Feliway were compared to placebo cats, whatever the room. Results The study demonstrated that the use of Feliway spray leads to significant (P = 0.01; Fisher s exact test) differences in cats usual behaviour, according to their owners, cats being easier to handle compared to previous consultations. With regard to stress, animals exposed to Feliway showed significantly lower Cat-Stress-Score levels than those treated with placebo (P = 0.02, Student s t-test). Difference to usual behaviour Easier to handle using Feliway 1 Easier to handle using Placebo 17 No difference/ More difficult to handle using Feliway 32 No difference/ More difficult to handle using Placebo Feliway Placebo Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Veterinary Practice Use

82 Cat-Stress-Score 6 5,5 5 4,5 4 3,5 3 2,5 2 1,5 1 0,5 0 Feliway Placebo 1,2 0,8 4 3,2 Mean Cat Stress Score Regarding the scale of handling, the scoring did not differ significantly between cats under the effect of Feliway spray and cats receiving placebo (p=0.1145; Student s t- test). The room factor influence on the cat s behaviour was analyzed through odds ratio estimates and showed no influence on the results on any of the assessed parameters. Conclusion This research shows that the use of Feliway spray on the examination table improves the welfare of cats by reducing their stress during veterinary consultations. Feliway spray significantly changed the behaviour of the cats in this study, and offers a simple and effective way to help decrease stress in cats during the consultation. Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Travel and New Environments

83 Recommendations for Use: Routine consultations The Feliway Diffuser is the most convenient formulation for use in waiting areas and consultation rooms to help comfort nervous patients. In presence of air conditioning plug in the diffuser away from the air-conditioner, vents, cold air returns, or exhaust fan. In addition, Feliway Spray can be applied to items in the consulting room 15 minutes before consultations to help reassure cats during examinations. Spraying a supply of towels that can be placed on the table at the start of the day can speed up the process. Before bringing the cat into the veterinary practice, it is recommended to use Feliway Spray in the cat carrier (please refer to recommendations for use of Feliway in transportation in former chapter) During hospitalisation The Feliway Diffuser is the most convenient formulation to use in the hospitalisation and recovery rooms. Empty and clean cages should also be sprayed with Feliway first thing every morning, at least 15 minutes before a cat is likely to be introduced to the cage: 1 spray to each of the 4 corners, 2 sprays to the floor and 2 sprays to the top of the cage. For long-term residents, the cage can be sprayed daily following normal cleaning procedures. However, it is important not to return the cat to the cage for at least 15 minutes to allow the alcohol to evaporate. Alternatively, bedding may be sprayed (again left for the necessary time) before being introduced to the cage. If you are introducing new sprayed bedding, ensure that at least some of the old familiar bedding is left with the cat to give added reassurance. In addition to the use of Feliway (Diffuser and/or Spray), loud noises and excessive numbers of people coming and going should be avoided. Ideally, cats should not be hospitalised in the same room as dogs. In addition to pheromone use within the veterinary clinic, many other modifications, often very simple, can be implemented to create a cat friendly practice (see below recommendations from feline reputable organisations) Ceva Santé Animale - Feliway and Adaptil Comprehensive References - Veterinary Practice Use

84 Feline Idiopathic Cystitis Feline lower urinary tract disease (FLUTD) describes a collection of conditions that can affect the bladder and/or urethra of cats. However, the majority (55-69%) of cases are idiopathic. Research over the last 30 years has failed to find a consistent cause for the inflammation in cases of feline idiopathic cystitis (FIC). However, it may result from alterations in the nervous and endocrine systems of the cat caused by an inability to cope with environmental stress 1, 2, 3, 4. Preferred Identified stressors include living with another cat with which the FIC sufferer is in conflict (i.e. cats belonging to different social groups), abrupt changes in diet, environment or weather, overcrowding, owner stress, or the addition of new pets or people to the household 5. Reducing feline stress should be the primary aim of any veterinary practitioner treating cats with recurrent cases of FIC. Feline facial pheromone (Feliway ) has been shown to help prevent and manage stress and its use to help reduce the occurrence and incidents of FIC is recommended by several feline practitioners and supported by the following publication. 1 Buffington C A, Pacak K, Increased plasma norepinephrine concentration in cats with interstitial cystitis, Journal of Urology, 2001; 165, Buffington C A, External and internal influences on disease risk in cats, Journal of the American Veterinary Medical Association, 2002; 220, Westropp J L, Buffington C A, Effects of feline interstitial cystitis on α2-adrenoreceptor-mediated signal transduction pathways, Proceedings of the 20th American College of Veterinary Internal Medicine, Dallas, Texas, 2002; Westropp J L, Buffington C A, Uncoupling of the noradrenergic-hypothalamic-pituitary-adrenal axis in stressed cats with interstitial cystitis, Proceedings of the 20th American College of Veterinary Internal Medicine, Dallas, Texas, 2002; Danielle A. Gunn-Moore, Feline Lower Urinary Tract Disease (FLUTD) Cystitis in Cats 2010 Feline Idiopathic Cystitis