Effects of preadoption counseling on the prevention of separation anxiety in newly adopted shelter dogs

Separation anxiety is one of the more prevalent and difficult to treat behavior problems in dogs. The associated behaviors can be undesirable to dog owners and damage the human animal bond, leading to relinquishment or return to an animal shelter. Due to the high prevalence of separation related problems in recently adopted shelter dogs, shelter staff hold a critical role in advising and educating owners on how to prevent separation anxiety post-adoption. The aim of this study was to propose a form of that preventive counseling as a means of preventing the development of separation anxiety in recently adopted shelter dogs. The efficacy of preadoption counseling in the education and prevention of separation anxiety problems was tested in a prospective, randomized, parallel-group study. Participants included 133 new owners of dogs 6 months of age and older. At the time of adoption, sixty-six of these owners were randomly selected to receive five minutes of counseling on the prevention of separation anxiety, while the remaining sixty-seven owners served as the controls. A follow-up survey regarding the signs associated with separation anxiety and other potentially related behaviors was conducted one month post adoption. Results showed that 19 owners reported their dogs as having separation anxiety. There was no significant effect of adoption counseling on the prevention of separation anxiety. Owners in both groups were equally as likely to perform most of the recommendations given during counseling. Dogs that were reported to have separation anxiety were significantly more likely than dogs without reported separation anxiety to show nervous or panicked behavior as the owner prepared to leave (P = 0.0001) and were more likely to be reported as being “needy” (P = 0.031). Having another dog in the home was not protective against the development of separation anxiety. Owners in the counseling group were more likely than those in the control group to put food inside a toy at the time of leaving the dog home alone (P = 0.0001), suggesting the counseling recommendations were indeed followed by the owners. Owner compliance supports the idea that counseling is a useful tool for owners. Separation anxiety is a disorder whose course may be difficult to alter in recently adopted shelter dogs using only basic, interventional information. Brief counseling and a toy do not effectively prevent the occurrence of this complex behavioral condition. Further investigation should be done to find more specific, effective prevention tools for owners to use in the home to minimize the development of separation anxiety and shelter should be prepared to provide interventional resources to owners whose dogs develop separation anxiety despite these efforts.     

Fluoxetine combined with clorazepate dipotassium and behaviour modification for treatment of anxiety-related disorders in dogs

The effectiveness of clorazepate dipotassium combined with fluoxetine and a behaviour modification programme for the treatment of anxiety disorders in dogs was investigated. Forty dogs with anxiety disorders were initially enrolled and 36 dogs completed the trial. Dogs were classified into two behavioural categories (anxious dogs with aggression and anxious dogs without aggression) according to their presenting complaints, and were also subdivided into males, females, juveniles and adults. The dog owners were provided with a behaviour modification plan for their dogs to be commenced in the first week of therapy. Clorazepate dipotassium was administered PO at 1.0 mg/kg every 24 h for 4 weeks, and fluoxetine was administered PO at 1.0 mg/kg every 24 h for 10 weeks. Therapy with both drugs was initiated simultaneously. Improvement was reported in 25/36 dogs. Significant differences in treatment effects were observed between anxious dogs with aggression and anxious dogs without aggression (P < 0.05). Positive correlations between owner compliance with the treatment plan and reported improvement achieved during three periods of study were also noted.     

Effects of reconcile (fluoxetine) chewable tablets plus behavior management for canine separation anxiety

Canine separation anxiety is a common behavioral problem presented to veterinarians. Associated behaviors are distressing to both dog and owner, have the potential to disrupt the human-companion animal bond, and may lead to euthanasia. The results of this study demonstrate the clinical efficacy and safety of Reconcile (fluoxetine, 1 to 2 mg/kg/day [0.45 to 0.91 mg/lb/day]), in conjunction with behavior management, for the treatment of canine separation anxiety. The beef flavored chewable formulation was palatable to treated dogs and easy to administer. This study provides to veterinarians and owners valuable information about an effective separation anxiety treatment plan that combines use of Reconcile with behavior modification.     

Evaluation of clomipramine as an adjunct to behavioural therapy in the treatment of separation-related problems in dogs

Forty-nine dogs showing signs of separation-related problems were randomly assigned to one of three groups: group A (15 dogs) received a placebo twice daily; group B (17 dogs) received clomipramine at 0.5 to 1.0 mg/kg twice daily; and group C (17 dogs) received clomipramine at 1.0 to 2.0 mg/kg twice daily. All the dogs also received behavioural therapy. Their owners were required to complete questionnaires about their dog's behaviour initially, and one, four and eight weeks after the treatment with clomipramine began. Bipolar ratings scales were used to monitor the frequencies of 'general', 'attachment-related' and 'separation-related' behaviours. Kruskal-Wallis tests and Kendall Rank correlations were used to determine any initial differences between the treatment groups, and the association between the initial scores and behavioural changes after one week of treatment with clomipramine. Extended Mantel-Haenszel statistics were used to evaluate the effects of clomipramine treatment versus the placebo, and Page's test was used to assess the effectiveness of behavioural therapy on its own. There were no significant differences in the demographic characteristics of the owners of the dogs assigned to the three groups. The dogs differed slightly in age between groups, and the dogs in the two clomipramine-treated groups were reported as showing problems at a significantly earlier age than those in the placebo group. Clomipramine treatment had a sustained suppressive effect on the dogs' general activity levels, and a more modest suppressive effect on their attachment-related tendency to want much physical contact with their owners. The typical signs of separation-related behaviour problems were not significantly affected by treatment with clomipramine, but behavioural therapy on its own was highly effective in reducing behavioural problems.     

Evaluation of treatments for separation anxiety in dogs

OBJECTIVE: To evaluate treatment outcome in dogs with separation anxiety and owner compliance with and perception of effectiveness of discharge instructions. DESIGN: Cohort study. ANIMALS: 52 dogs with separation anxiety. PROCEDURE: Sex, age at which the owner obtained the dog, age at which separation anxiety was first noticed, age at behavioral examination, and discharge instructions were obtained from medical records of each dog. Between 6 and 64 months after the behavioral examination, owners were contacted by telephone and questioned about the outcome of treatment, their compliance with discharge instructions, and their perception of the effectiveness of each instruction. RESULTS: Thirty-two (62%) dogs had improved, whereas 20 were the same, were worse, or had been euthanatized or given away. Mixed-breed dogs were significantly less likely to improve than purebred dogs. Compliance varied according to discharge instruction. Significantly fewer dogs with owners that were given > 5 instructions improved or were cured, compared with those with owners given fewer instructions. Twenty-seven dogs were also treated with amitriptyline or other medication; 15 (56%) improved. CONCLUSIONS AND CLINICAL RELEVANCE: Owners complied with instructions that involved little time such as omitting punishment and providing a chew toy at the time of departure. Owners were also willing to increase the dog's exercise but were not willing to uncouple the cues of departure from real departures or desensitize the dog to impending departure. Administration of psychoactive medication may be necessary to augment behavior modification techniques designed to reduce separation anxiety in dogs.     

Use of clomipramine in treatment of obsessive-compulsive disorder, separation anxiety and noise phobia in dogs: a preliminary, clinical study

OBJECTIVE: To evaluate the efficacy and tolerance of a treatment protocol for obsessive-compulsive disorder, separation anxiety and noise phobia in dogs. DESIGN: A study was undertaken to assess clinical responses in 24 dogs diagnosed with one or more of three behavioural disorders stated above to a treatment regimen that included clomipramine and behaviour modification. PROCEDURE: A detailed behavioural and clinical history was obtained for each dog. Obsessive-compulsive disorder was diagnosed in nine cases: primary presenting complaints were tail-chasing, shadow-chasing, circling and chewing; one case was diagnosed with concurrent separation anxiety. Separation anxiety was diagnosed in 14 cases: presenting complaints included destruction, vocalisation and escaping in the absence of the owner; four cases also exhibited noise phobia. The study also included one dog diagnosed with noise phobia only and another with inappropriate fear responses. Clomipramine was administered orally twice daily. The starting dose was 1 to 2 mg/kg bodyweight. The dose was increased incrementally to a maximum of 4 mg/kg if needed. A behaviour modification program was designed and the owner instructed on its implementation. Dogs continued medication for at least 1 month after clinical signs disappeared or were acceptably reduced, then withdrawal of medication was attempted by decreasing drug dosage at weekly intervals while behaviour modification continued. RESULTS: The presenting clinical sign was largely improved or disappeared in 16 dogs, 5 demonstrated slight to moderate improvement and the behaviour was unchanged in 3. Clomipramine withdrawal was attempted in nine cases: this was successful in five. CONCLUSION: Clomipramine was effective and well-tolerated in controlling signs of obsessive-compulsive disorder and/or separation anxiety and/or noise phobia in 16 of 24 assessable cases, when used in combination with behaviour modification, and improvement in clinical signs was noted in 5 others.     

Effects of clomipramine hydrochloride on dominance-related aggression in dogs.

OBJECTIVE: To compare effects of the serotonergic drug clomipramine hydrochloride with those of placebo for treatment of dominance-related aggression in dogs. DESIGN: Randomized, placebo-controlled, double-blind clinical trial. ANIMALS: 28 neutered dogs > 1 year old with dominance-related aggression. PROCEDURE: Dogs displaying > or = 3 aggressive episodes/wk toward > or = 1 human family member in response to identifiable behavioral triggers were included in the study. Owners were instructed not to change patterns of interaction with their dogs during the study. After 2 weeks of baseline observations, dogs were treated for 6 weeks with clomipramine (1.5 mg/kg [0.7 mg/lb] of body weight, q 12 h; n = 15) or placebo (13). Responses to triggers were assigned the following aggression scores: no response, 0; growl or lip curl, 1; snap or bite, 2. Mean scores for responses to triggers were obtained during the 2-week pretreatment period (baseline) and during the first and second weeks, third and fourth weeks, and fifth and sixth weeks of treatment. At the end of the study, owners assigned a score designed to evaluate their overall perceived change in aggressiveness; this was referred to as the global score. RESULTS: Mean aggression scores decreased at the fifth and sixth week of treatment in both groups, compared with baseline scores. However, mean scores between groups were not different. Global scores, assigned by the owner, generally reflected changes in mean aggression scores. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with placebo, clomipramine administered to dogs at the dosage recommended for treatment of separation anxiety did not reduce aggressiveness toward human family members.     

Time requirement and effect on owners of home-based management of dogs with severe chronic spinal cord injury

The aim of this study was to provide quantitative data on time commitment needed for care of dogs with chronic severe spinal cord injury (SCI) at home and assess effect on the owner's home lives. It was not a study aimed at assessing the quality of life (QOL) of the dogs as this has previously been examined, although a small amount of data was collected on this aspect.A questionnaire was sent to 40 owners of dogs with clinically complete chronic SCI (defined by lack of observable response to a noxious stimulus applied to the hind limbs, the absence of voluntary hind limb locomotor function, and urinary and fecal incontinence for more than 9 months at the time the study was conducted). Owners were asked to quantify the time spent exercising their pet, managing urinary and fecal incontinence and giving general skin and fur care. Other questions sought to determine the effect on family relationships.The study population included 27 dachshunds and 10 other breeds. Twenty-six questionnaires were returned for analysis, giving a response rate of 65%. Owners spent between 2 and 44 hours in total per week managing their dog (median, 14 hours), with between 1 and 30 hours spent on mobility management (median, 10 hours) and between 0 and 16 hours (median, 3 hours) on incontinence. About 92% of owners were living with a partner, and at least one in the couple did not work full time, 84% had no children younger than 16 years, 64% either currently or previously owned another dog, and 73% declared that they had not considered euthanasia as an option at the time of the SCI.Twenty owners strongly agreed that the work involved was worthwhile, and 16 owners felt that the work involved had strengthened the bond between them and their pet. One owner felt that the care required had reduced their own QOL and 2 owners reported serious family problems. The dogs studied form a particular subset of cases because they had been cared for by their owners for at least 9 months. However, this study provides information that will aid informed decision making by owners and veterinarians at the time of a dog SCI, providing an indication of what can be expected in the chronic phase of SCI.     

Risk factors and behaviors associated with separation anxiety in dogs

OBJECTIVES: To determine potential risk factors and behaviors associated with separation anxiety and develop a practical index to help in the diagnosis of separation anxiety in dogs. DESIGN: Case-control study. ANIMALS: 200 dogs with separation anxiety and 200 control dogs with other behavior problems. PROCEDURES: Medical records were reviewed for signalment, history of behavior problems, home environment, management, potentially associated behaviors, and concurrent problems. RESULTS: Dogs from a home with a single adult human were approximately 2.5 times as likely to have separation anxiety as dogs from multiple owner homes, and sexually intact dogs were a third as likely to have separation anxiety as neutered dogs. Several factors associated with hyperattachment to the owner were significantly associated with separation anxiety. Spoiling activities, sex of the dog, and the presence of other pets in the home were not associated with separation anxiety. CONCLUSIONS AND CLINICAL RELEVANCE: Results do not support the theory that early separation from the dam leads to future development of separation anxiety. Hyperattachment to the owner was significantly associated with separation anxiety; extreme following of the owner, departure cue anxiety, and excessive greeting may help clinicians distinguish between canine separation anxiety and other separation-related problems.     

Free‐Roaming Dogs in Nepal: Demographics,Health and Public Knowledge,Attitudes and Practices

In Nepal, most dogs are free to roam and may transmit diseases to humans and animals. These dogs often suffer from malnutrition and lack basic health care. Minimal information is available about their demographics and about public attitudes concerning dogs and diseases. We carried out a study in Chitwan District (central Nepal), to collect baseline data on free‐roaming owned dog demographics, assess knowledge, attitudes and practices of dog owners concerning dogs and rabies, evaluate rabies vaccination coverage and anthelmintic treatment of dogs, measure dogs' response to rabies vaccination and assess dog health through body condition scores and parasites. We conducted household interviews with owners of free‐roaming female dogs (n = 60) and administered dogs with rabies vaccination and anthelmintics. Dog owners regularly fed free‐roaming dogs but provided minimal health care; 42% of respondents did not claim ownership of the dog for which they provided care. We collected skin, faecal and blood samples for parasite identification and for measuring rabies virus‐specific antibodies. Ninety‐two per cent of dog owners were aware of the routes of rabies virus transmission, but only 35% described the correct post‐exposure prophylaxis (PEP) following a dog bite. Twenty‐seven per cent of the dogs had measurable rabies virus‐specific antibody titres and 14% had received anthelmintics in the previous year. Following rabies vaccination, 97% of dogs maintained an adequate antibody titre for ≥6 months. Most dogs appeared healthy, although haemoprotozoans, endoparasites and ectoparasites were identified in 12%, 73% and 40% of the dogs, respectively. Poor skin condition and parasite load were associated. Seventy‐four per cent of the females had litters in 1 year (mean litter size = 4.5). Births occurred between September and February; we estimated 60% mortality in puppies. We concluded that vaccination coverage, PEP awareness and anthelmintic treatment should be emphasized in educational programmes focussed on animal welfare, veterinary and public health.     

Frequency of nonspecific clinical signs in dogs with separation anxiety, thunderstorm phobia, and noise phobia, alone or in combination

OBJECTIVE: To determine the frequency of nonspecific clinical signs in dogs with separation anxiety, thunderstorm phobia, noise phobia, or any combination of these conditions and determine whether these conditions are associated in dogs. DESIGN: Case series. ANIMALS: 141 dogs. PROCEDURE: Diagnoses were established using specific criteria. Owners of dogs completed a questionnaire on how frequently their dogs exhibited destructive behavior, urination, defecation, vocalization, and salivation when the owners were absent and the types and frequency of reactions to thunderstorms, fireworks, and other noises. RESULTS: Associations of the 3 conditions and of various nonspecific clinical signs within and between diagnoses were nonrandom. The probability that a dog would have separation anxiety given that it had noise phobia was high (0.88) and approximately the same as the probability it would have separation anxiety given that it had thunderstorm phobia (0.86). However, the probability that a dog would have noise phobia given that it had separation anxiety (0.63) was higher than the probability that it would have thunderstorm phobia given that it had separation anxiety (0.52). The probability that a dog would have noise phobia given that it had thunderstorm phobia (0.90) was not equivalent to the converse (0.76). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that dogs with any of these conditions should be screened for the others. Interactions among these conditions are important in the assessment and treatment of dogs with > 1 of these conditions. Responses to noise were different from those to thunderstorms, possibly because of the unpredictability and uncertainty of thunderstorms.     

Dog attachment to man: A comparison between pet and working dogs

Shared activities are known to create a good relationship between dog and man. Therefore, it can be expected that animals working in harness with their handlers, such as search and rescue dogs, show a higher attachment to man.The aim of the current research was to assess whether there are differences between pet and working dogs in the attachment to owners/handlers.Forty dogs were involved, 26 pets and 14 search and rescue dogs (taken home when not working). Their attachment to owners/handlers was analyzed by using a modified version of the Ainsworth Strange Situation Test and a recall test, while owners and handlers filled in a questionnaire and were scored on the Lexington Attachment to Pets Scale.Statistical analysis revealed no statistically significant differences between pet and working dogs for behaviors indicating an attachment bond: behavior oriented to door/chair/shoe during the absence of owner/handler (which represents “search of absent person”; U = 132.000, P = 0.156), contact with/proximity to owner/handler (i.e., “contact maintenance effect”; U = 157.000, P = 0.478), whining during owner's/handler's absence (“protest at the separation”; U = 147.000, P = 0.288), and individual play (U = 146.000, P = 0.288) and exploration (U = 138.500, P = 0.215) in presence of owner/handler, representing the “secure base effect.”Despite the lack of statistical differences, the formulated hypothesis may be not completely rejected, as a trend of a higher attachment in search and rescue dogs existed. It can be concluded that in carefully owned dogs, the level of attachment is increased by working as a search and rescue dog, but the difference does not lead to statistically relevant results.     

Hybrid balloon valvuloplasty for management of severe mitral stenosis in four symptomatic,adult dogs

Four adult dogs weighing <10 kg presented for the evaluation of severe mitral valve stenosis with clinical signs. Owing to the size of the dogs, a hybrid surgical and interventional approach was utilized for balloon valvuloplasty. A left lateral thoracotomy was performed to allow direct entry through the left atrial wall. Transesophageal echocardiography was utilized for the entirety of the procedure in all dogs, and fluoroscopy was additionally used in two dogs. One dog had mild to moderate intra-operative bleeding from the left atrial wall during the procedure, but no other intra-operative complications were observed. No dogs developed a clinically relevant amount of worsened mitral regurgitation. Based on mitral leaflet mobility and transmitral flow profiles, there was perceived improvement in all four dogs. One dog died 6 h after extubation due to respiratory arrest. The remaining dogs survived to discharge and had resolution of clinical signs at home and discontinuation of heart failure medications. One dog died of an unknown cause at five months and another developed atrial fibrillation, and the owners elected to euthanize at ten months after the procedure. One dog continues to do well six months after the procedure as of the time of this writing. Hybrid balloon valvuloplasty can be a viable management option for small breed dogs with severe mitral stenosis exhibiting clinical signs, and both transesophageal echocardiography and fluoroscopy can be used intra-operatively to assist in successful procedural outcomes.     

Risk factors associated with interdog aggression and shooting phobias among purebred dogs in Denmark

The prevalence of behaviour problems is reported from a questionnaire study among members of the Danish Kennel Club (DKC). In total, 4359 dog owners were included in the analyses. With logistic regression, we analysed four behaviour problems: dominance towards the owner, interdog dominance aggression, separation anxiety and shooting phobia. Compared to Labrador Retrievers, the following breeds and breed groups had higher odds of being reported to have interdog dominance aggression: Belgian Sheepdogs, Dachshunds, Dalmatians, German Shepherds, Hovawarts, Pinschers, Rottweilers, Scent dogs and Spitz dogs. Poodles, retrieving/flushing dogs, Sheepdogs, Spitz dogs and terriers had higher odds of shooting phobia. The odds of interdog dominance aggression were higher among dogs owned by younger dog owners compared to dogs owned by older dog owners. Dogs living in the capital area of Copenhagen had increased odds of interdog dominance aggression as compared to dogs living in other parts of Denmark. Dogs belonging to owners with limited knowledge of the breed before acquiring the dog had higher odds of interdog dominance aggression. Dogs attending obedience training classes had reduced odds of shooting phobia. Dogs belonging to dog breeders had reduced odds of being reported to have the investigated behaviour problems.     

Use of fluoxetine,diazepam, and behavior modification as therapy for treatment of anxiety-related disorders in dogs

The objective of this study was to evaluate the use of fluoxetine, diazepam, and behavior modification for the treatment of a variety of anxiety disorders in dogs of different breeds, ages, and sexes that presented to a university veterinary behavior clinic. Forty dogs were enrolled in the study, and 34 completed it. The dogs were grouped into 2 major diagnostic categories, aggressive and anxious, according to the presenting signs. Moreover, the dogs further subdivided into 4 groups: neutered, intact, juveniles, and adults. Diazepam was administered orally, at a dosage of 0.3 mg/kg once a day for 4 weeks; fluoxetine was administered orally at a dosage of 1 mg/kg once a day for 10 weeks. The drugs were started simultaneously. The owners were given a behavior modification plan for their dogs that started from the first week of therapy. The behavior of the subjects was evaluated at 3 points in time. Clinical response was assessed by the supervising veterinarian and the owners. There were no significant differences (P > 0.05) between the groups studied in relation to the improvement achieved. There was a positive correlation (r > 0.44) between owner compliance with the treatment and the values obtained for the improvement achieved for each period. Clinical signs largely improved or were eliminated in 13 dogs (38%), 8 dogs (26%) showed moderate improvement, 5 dogs (12%) were slightly improved, and there were 8 dogs (24%) with no changes in clinical signs.     

Clomipramine and selegiline: do they influence impulse control?

Anxiety disorders in dogs are often accompanied by loss of impulse control and can result in inappropriate behaviour such as destructiveness, excessive barking and aggression. The reduction of these undesirable actions is the focus of behaviour therapy. Clomipramine and selegiline have been approved for the treatment of separation anxiety in dogs, but there are anecdotal reports that they produce inconsistent therapeutic effect. Hence, the aim of this study was to verify the efficacy of clomipramine and selegiline for regulating impulse control by using a rat model based on the delay of reward procedure. The principle is that the animal has to decide between an immediate small food reward, normally preferred by impulsive animals, and a delayed large food reward. In this study, acute effects of clomipramine (0.3-10.0 mg/kg), selegiline (0.3-3.0 mg/kg), and diazepam (1.0-3.0 mg/kg) on the impulsive behaviour of two breeding lines of rats with different anxiety-related behaviour were investigated. Neither clomipramine nor selegiline had an effect on impulse control in either breeding line. However, motor activity was decreased by clomipramine and increased by selegiline. Diazepam led to an increase in impulsive behaviour of one rat line concomitant with an increase in motor activity. The results of this rat model for studying impulsive behaviour suggest that a single administration of selegiline and clomipramine has no influence on impulsive behaviour.     

The Perceptions of Dog Intelligence and Cognitive Skills (PoDIaCS) Survey

Dog cognition research is expanding, but few studies have examined people's perceptions of specific cognitive abilities in dogs. The aim of this study was to explore owner perceptions of dog cognitive abilities across different cognitive domains and to determine whether these were associated with the dog–owner relationship. We developed an online questionnaire and analyzed the results from 565 dog owners. Dog owners generally indicated the belief that dogs are socially intelligent and possess the capacity to learn social and general cognitive skills. One quarter of dog owners agreed or strongly agreed that dogs were smarter than most people, and 45.7% indicated the belief that a dog's mental ability is equal to “3-5 year old human children.” Perceived emotional owner–dog closeness correlated with all cognition ratings. A better understanding of dog cognitive abilities may help owners interpret dog behavior more appropriately, which may lead to a reduction in the number of dogs relinquished to shelters because of behavioral problems.     

Effects of clomipramine hydrochloride on heart rate and rhythm in healthy dogs

OBJECTIVE: To determine the effects of clomipramine hydrochloride on heart rate and rhythm in dogs. ANIMALS: 17 healthy Beagles. PROCEDURES: In experiment 1, 8 dogs received placebo or clomipramine (20 mg/kg of body weight, q 24 h, PO) for 7 days in a 2-way crossover design. In experiment 2, 9 dogs were evaluated for 48 hours before and 24 hours after oral administration of clomipramine (4 or 12 mg/kg) in a 2-way crossover design. Electrocardiogram and heart rate were monitored continuously by use of telemetry. RESULTS: A significant diurnal rhythm in heart rate was detected; minimum values were recorded at night. Administration of 20 mg of clomipramine/kg induced a significant reduction in heart rate, with peak effect achieved approximately 12 hours after dosing. Administration of 4 or 12 mg of clomipramine/kg did not result in significant changes in heart rate. Sinoatrial and second-degree atrioventricular block and ventricular escape beats were observed during periods of slow heart rate in more dogs that received clomipramine (3 to 4 of 8 dogs), compared with dogs that received placebo (1 to 2 of 8 dogs), but this difference was not significant. CONCLUSIONS AND CLINICAL RELEVANCE: Short-term administration of clomipramine induced benign cardiovascular effects in dogs rather than the potentially dangerous arrhythmias or tachycardia reported following administration of tricyclic antidepressants to humans. Precautions regarding cardiovascular effects may not be needed for the use of clomipramine in healthy dogs.     

Pharmacokinetic comparison of oral tablet and suspension formulations of grapiprant,a novel therapeutic for the pain and inflammation of osteoarthritis in dogs

A new anti‐inflammatory drug for pain (grapiprant) was recently shown to have minimal side effects following chronic (9‐month) daily oral dose of 6 or 50 mg/kg suspension. The current study compares the pharmacokinetics of the formulation used in the chronic safety study to those of the tablet formulation that will be marketed upon FDA approval. Sixteen Beagle dogs were randomized to receive single doses of either 6 or 50 mg/kg grapiprant as both suspension and table formulations within a cross‐over design with a 15‐day washout. Clinical observations were vomiting in one high‐dose suspension dog and loose stools in two dogs, one in each 6 mg/kg formulation group. For both formulations, grapiprant reached a maximum concentration within two hours. The tablet formulation had better bioavailability, with AUC_last values 34% higher at 6 mg/kg and 64% higher at 50 mg/kg compared to the suspension. Results on Day 0 were similar to those reported on Day 15, suggesting little to no accumulation. Using conversion factors of 1.34 and 1.64, these findings suggest that the 6 and 50 mg/kg suspension doses are equivalent to 4.5 and 30 mg/kg tableted doses, respectively. Combining these findings with the 9‐month safety study demonstrates that safety was evaluated at doses approximately 15‐fold above the demonstrated therapeutic dose of 2 mg/kg and 10‐fold over the ‘safety dose’, defined as the maximum dose a dog of any body weight could receive when dosed at 2 mg/kg with whole or half‐tablets.