Abstract
Separation anxiety is a common behavioral problem in dogs. Treatment is based on developing a behavior modification protocol that gradually desensitizes and counter-conditions the dog to being left alone, by rewarding calm, relaxed behavior. Judicious use of pharmacotherapy can be a useful adjunct to a behavior modification program.
A 2-year-old, neutered male pointer cross was presented because of excessive vocalization when left alone. The dog's early history was unknown, as it had been a stray, adopted from a local shelter 2 wk prior to presentation. The dog had been vaccinated at the shelter against canine distemper, canine infectious hepatitis, parvo-, parainfluenza, and rabies viruses. The dog was exercised on a leash for approximately 0.5 h, 4 times daily, and was offered dry food (Science Diet Adult Maintenance, Hill's Pet Nutrition Canada, Mississauga, Ontario), 1 cup, q12h. The owners reported that the dog's appetite was poor. The main complaint at presentation was the constant barking, howling, and whining, when left alone, that had begun immediately after the dog was adopted. One week after adoption, the dog also began scratching at and damaging the front door. The dog showed no other destructive behavior when left alone, never urinated or defecated in the house, and showed no anxious behavior when left with people other than the owners. An attempt was made at crate training for the 1st week after adoption, but the dog showed profound anxiety when left alone in the crate for 2 h, and later refused to enter it. The problem was being managed by never leaving the dog at home alone. The dog was quiet, calm, and affectionate when the owners were with him. However, when he recognized signs associated with their leaving (getting keys, putting shoes on, turning the television off), he sat at the door, paced, whined, and periodically licked his left stifle and foreleg.
When examined 2 wk after adoption, the dog was alert, responsive, and in good body condition. Rectal temperature (38.5°C), pulse (80 bpm), and respiratory rate (16 breaths/min) were within the normal ranges. Alopecia, without erythema, inflammation, or granulation tissue, was apparent on the left stifle and foreleg. Results of a complete blood cell (CBC) count (QBC VetAutoread Hematology System; IDEXX Laboratories, Toronto, Ontario) and serum biochemical profile, including serum sodium, potassium, and chloride (Vet-test; IDEXX Laboratories), were unremarkable.
A diagnosis of separation anxiety was made on the basis of the history: the physical and behavioral signs of distress occurred only when the owners were preparing to leave or during their absence, and damage was directed at their exit point (1,2).
No attempt was made to deal directly with the signs of vocalization and destruction. A desensitization and counter-conditioning program was implemented to eliminate or reduce anxiety associated with the owners' departure and absence. First, simple obedience commands, including “sit,” “down,” and “stay,” were taught and practised for food rewards. The dog's anxiety often began with the first cue that the owners were leaving, so the next step was to uncouple the departure cues from the actual departure and to reinforce calm, relaxed behavior (2,3). For example, the owners gave the commands “down” and “stay,” picked up their keys, and then sat down. Relaxed behavior in the dog was rewarded and anxious behavior was ignored, never punished. The owners were instructed to repeat this exercise as many times as possible, using different departure cues. Next, gradual departures were practised (Table 1).
Table 1.
The goal was for the owners to be able to perform the activities listed in Table 1 without the dog becoming anxious. If the dog was relaxed when the owners left for 5 s, but was anxious at 10 s, the 5-second departures were to be repeated several times before advancing, and then advances were made in smaller increments, for example, by using a 7-second departure instead of a 10-second one. The dog's behavior was a measure of the degree of progress and an indicator of how the program would have to be adapted to the individual dog. Usually, a dog that is relaxed and calm when left alone for 30 min will be able to tolerate longer intervals (2,3). It was explained to the owners that this program requires a significant investment in time and patience. A dog must experience minimal anxiety, so it should not be left alone longer than the longest interval it can tolerate without anxiety.
Two weeks after the initial consultation, the owners were able to leave the dog alone for up to 1 h without vocalization, which was monitored by leaving a cassette tape recording. However, when he was left for 2 h, anxiety recurred, with vocalization and damage to the front door. The use of an anxiolytic drug, in addition to the behavior modification program, was recommended. An electrocardiogram (ECG) was recommended before the treatment was started, but it was declined. Clomipramine (Clomicalm; Novartis Animal Health Canada, Mississauga, Ontario) was prescribed, 1 mg/kg bodyweight (BW), PO, q12h, for 2 wk; then 2 mg/kg BW, q12h, for 2 wk; then 3 mg/kg BW, q12h, which was to be the maintenance dose.
Separation anxiety is most commonly seen in dogs adopted after being abandoned when young, and in older dogs that experience a significant change in their household. Because dogs form strong social attachments to humans, separation anxiety is believed to be a distress response related to their separation from a highly social state (2). Attachment behaviors are necessary in highly social species to maintain social contact between individuals, as well as between parent and offspring (1).
Inappropriate elimination, destruction, and vocalization are hallmark behaviors of separation anxiety; however, they are nonspecific signs. Both physical and behavioral causes must be considered, and disease processes ruled out. For example, differential diagnoses for inappropriate elimination should include physical incontinence associated with conditions such as lower urinary tract infection, cystitis, hormonal incontinence, urolithiasis, and neurogenic disease. A complete physical examination, including urinalysis, is necessary to rule out physical causes of incontinence. As well, other causes of apparent incontinence must be considered, including incomplete housebreaking, marking, fear, excitement, submissive elimination, and limited access to appropriate elimination areas. Destructive behavior may occur with play and normal puppy behavior, with overactivity, or as a fear response or reaction to arousing stimuli. Vocalization may be a response to play, a response to fear or aggression, or a response to external stimuli, such as sirens, bells, other dogs, or humans (1,2). McCrave (1) compared the features of separation anxiety with those of other behavioral problems.
Separation anxiety is a panic response, similar to human panic attacks in that the event or circumstance inducing an episode of anxiety probably does not cause continuation and progressive worsening of anxiety under those same circumstances. Rather, the memory of how the individual felt during the inducing circumstances reinforces the cycle. Antianxiety drugs are useful in breaking this cycle, and may allow a desensitization and behavior modification program to be more effective (4). In this case, because of the high level of client compliance and the age and health status of the dog, the use of behavioral pharmacology as an adjunct to behavior modification was considered safe. Clomipramine was an appropriate choice, as it does not interfere with short-term memory and is licensed for treatment of separation anxiety in dogs. The most common side effect is gastrointestinal upset; slowly increasing the dose may minimize this and other potential side effects (2,4). These clients were informed that the antidepressant effects of clomipramine might not be apparent for up to 3 wk, and that after successful behavior modification with adjunctive pharmacotherapy, the dog could either be weaned off the drug, or the dose could be reduced to a minimal effective dose. The recommended procedure is to continue the drug for 1 mo beyond the end of the training program, then to gradually withdraw it over a 2- to 4-week period (5).
Clomipramine hydrochloride is a member of the tricyclic class of antidepressants (TCAs); it is a potent serotonin (5-hydroxytryptamine) and norepinephrine reuptake inhibitor with anxiolytic effects. The main effects of TCAs are sedation, peripheral and central anticholinergic actions, and potentiation of central nervous system (CNS) biogenic amines by presynaptic receptor blockade (4,6). It is this last effect, which results in an increased concentration of transmitter monoamines at the receptor site, that is believed to be responsible for the antidepressant effects of TCAs. The monamine neurotransmitters (serotonin, dopamine, and norepinephrine) are concentrated in the midbrain, hypothalamus, and limbic system, a part of the brain that is thought to be active in control and expression of emotions (6).
Many TCAs also have potent antimuscarinic, anti-α1-adrenergic, and antihistaminic activity. The anticholinergic effects caused by muscarinic receptor blockade may result in side effects, such as mydriasis, dry mouth, reduced tear production, urine retention, and constipation. Sedative effects are probably secondary to anticholinergic and antihistaminic actions. Cardiovascular effects include tachycardia, orthostatic hypotension, and slowing of cardiac conduction, resulting in widening of the QRS complex (4,6,7). Other electrocardiographic (ECG) abnormalities that may be noted in dogs include flattened T waves, depressed ST segments, and prolonged PR intervals (4,7). Tricyclic antidepressants are highly lipid soluble and over 50% protein bound. They are well absorbed from the gastrointestinal tract and undergo significant first-pass effects. Plasma levels peak 8 to 12 h after the last dose and reach steady state levels after 5 to 7 d at the same dosage (4). Metabolism occurs primarily by hepatic demethylation, aromatic hydroxylation, and glucuronide conjugation; excretion is via bile and urine (4,6,7).
Before clomipramine is dispensed for a dog, a full physical examination is warranted, including a CBC count, a serum biochemical analysis, urinalysis, and an ECG. Use of any TCA is contraindicated with concomitant use of monoamine oxidase inhibitors, and because of their anticholinergic effects, TCAs should be used with caution in patients with decreased gastrointestinal motility, urinary retention, cardiac arrhythmia, or increased ocular pressure (4,7). Tricyclic antidepressants may have additive effects in patients treated with other drugs having anticholinergic or central nervous system depressant effects, or drugs known to inhibit metabolism, such as cimetidine or cisapride, and the risk of agranulocytosis is increased in dogs on thyroid supplementation (4,7). Regular monitoring of liver enzymes is recommended. High doses of clomipramine are associated with hepatotoxicity, convulsions, and cardiac abnormalities (4).
Separation anxiety is a common behavioral problem in dogs; it is estimated to comprise 20% to 40% of the average behavioral consultant's caseload (1). Psychotropic drugs are being used more commonly in veterinary behavioral medicine as information is extrapolated from human medicine, and research explores the potential use and efficacy of these agents in animals (4,6).
Footnotes
Acknowledgment
I thank Drs. K. Houpt, J. Prescott, K. Streib, and M. Cochran for their support, encouragement, and invaluable mentorship. CVJ
Michelle Lem will receive an animalhealthcare.ca fleece vest courtesy of the CVMA.
Dr. Lem's current address is Orleans Veterinary Hospital, 2000 Tenth Line Road, R.R. #2, Orleans, Ontario K1C 1T1.
References
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