Separation anxiety is one of the most common and most devastating behavioral conditions diagnosed world-wide in pet dogs. In the absence of treatment, affected dogs are often relinquished or euthanized. As is true for most behavioral conditions, the signs associated with separation anxiety are non-specific and often associated with other anxieties and phobias. Noise/storm phobias are among the most commonly recognized canine diagnoses associated with panicky or phobic responses. No data exist on relative incidence of these problems. Based on the findings of a preliminary study finding a high concordance between dogs who exhibited signs of separation anxiety and those who met the criteria for noise or thunderstorm phobias, a detailed study¹ found an important correlation between these phobic responses and separation anxiety that suggests that the presence of one condition can affect the development and outcome of other related conditions.

In this case one can postulate, but not yet know that 1) reactions to noise may predispose dogs to other anxiety related conditions, and 2) the interaction of the 2 conditions may have time penetrance, and the longer an animal has been affected with one condition, the more at risk it might be either for a more complex form of the conditions (e.g., a greater number or intensity of signs). Early treatment of these conditions is important. Finally, associations of any anxiety-related conditions with noise are important.

In the example of separation anxiety and noise and thunderstorm / storm phobia the following definitions of the conditions were used to screen all patients for the relevant diagnoses² and to monitor for non-specific signs that may help us classify response groups^3,4:

1.  Separation anxiety: Necessary condition - physical or behavioral signs of distress exhibited by the animal only in the actual absence of, or lack of access to (virtual absence) the client; Sufficient condition - consistent, intensive destruction, elimination, vocalization, or salivation exhibited only in the virtual or actual absence of the client; behaviors are most severe close to the separation, and many anxiety-related behaviors (autonomic hyperactivity, increased motor activity, and increased vigilance and scanning) may become apparent as the client exhibits behaviors associated with leaving.

2.  Noise phobia: Necessary and sufficient conditions - sudden and profound, non-graded, extreme response to noise, manifest as intense, active avoidance, escape, or anxiety behaviors associated with the activities of the sympathetic branch of the autonomic nervous system; behaviors can include catatonia or mania concomitant with decreased sensitivity to pain or social stimuli; repeated exposure results in an invariant pattern of response.

3.  Thunderstorm / storm phobia: Necessary and sufficient conditions - sudden and profound, non-graded, extreme response to thunderstorms or any aspect of them (e.g., wind, noise, lightening, changes in barometric pressure, rain, darkness, ozone level changes, et cetera) noise, manifest as intense, active avoidance, escape, or anxiety behaviors associated with the activities of the sympathetic branch of the autonomic nervous system; behaviors can include catatonia or mania concomitant with decreased sensitivity to pain or social stimuli; repeated exposure results in an invariant pattern of response.

Elimination, destruction, and vocalization are the most obvious and hence the most commonly reported behaviors associated with separation anxiety. It's important to realize that clients complain about these behaviors because they are easy to recognize and are problems for the client. However, it is less easy to recognize dogs that are distressed when left, but exhibit less obvious signs like withdrawal and inactivity, salivation, soft whimpering (or frank barking and howling if there are no near neighbors), and pacing. These dogs are also painfully affected by separation anxiety, but their problems are not problems for the clients, so they seldom get help. With these dogs included, the population of dogs with separation anxiety, while unknown, is likely to be large indeed, and all dogs can benefit from treatment.

The interaction of multiple pathological responses to noise likely may reflect an altered, dysfunctional, underlying neurochemical substrate, or is the result of one. The extent to which such dynamic interactions shape expressed behavioral phenotypes is supported by differential responses to behavioral medications.^5-7 The newer psychotropic medications [tricyclic antidepressants (TCAs), selective serotonin re-uptake inhibitors (SSRIs), and monoamine oxidase inhibitors (MAO-Is)] utilize the same second messenger systems and transcription pathways that are used to develop cellular memory or to "learn" something via mediation and induction of long-term potentiation (LTP) in the CA1 region of the hippocampus.^8,9

Some dogs respond either more quickly to a stimulus, or react more intensely to a given stimulus than do other dogs. This "hyper-reactivity" is probably truly pathological and represents yet another phenotypical manifestation of some neurochemical variation associated with anxiety. If so, the more frequently the dog reacts to the anxiety provoking stimulus, the worse and more rapid the response. At some point any exposure can result in a full-blown, non-graduated anxious reaction in which true panic may be involved. Accordingly, anticipation and early treatment is critical for these individuals, again supporting the concept that behavioral phenotype and underlying neurochemical response are linked in a dynamic way. Early intervention can only be accomplished by understanding the spectrum of signs exhibited in related conditions. If dogs follow the pattern common for co-morbid diagnoses as is found in humans, longer persistence of the signs and a less favorable overall outcome may be one outcome of co-morbidity.^10-11 In the clinic population studied, the conditional probability that a patient has separation anxiety, given that they have noise phobia is high (88%) and approximately the same as if they have thunderstorm phobia (87%). However, the probability that a patient has noise phobia is higher (74%) than the probability that they have storm phobia (61%), given that either have separation anxiety. These data, combined with the finding that the probability of having a noise phobia given a thunderstorm phobia is not equivalent to the converse (90% vs. 76%), supports the hypothesis that neurochemical responses to noise are different from those to thunderstorms, if the behavioral phenotypes or endophenotypes are manifestations of repeated exposure and LTP. The property of unpredictability / uncertainty associated with thunderstorms may have a role in shaping the neurochemical and behavioral responses to anxiety provoking situations, suggesting future areas of exploration for understanding anxiety-related responses in dogs.

Treatment must involve behavior modification, and medication to relieve distress. Only medication is discussed here.

When considering the combined use of TCAs or SSRIs with benzodiazepines for dogs with 2 diagnoses or profound, daily noise reactivity, the first medication of choice may be amitriptyline (1–2 mg / kg po q. 12 h x 30 d to start) because it is cheap, non-specific, and will show an effect within a month. However, it's lack of specificity for certain receptors means that it is often not the best medication by itself unless the problem has just started. For dogs who are severely affected and, or have been affected for some time, more specific medications may help. Fluoxetine (1 mg / kg po q. 24 h x 8 weeks, to start), sertraline (1+ mg / kg po q. 12–24 h), or clomipramine (1 mg / kg po q. 12 h x 14 d, then 2 mg / kg po q. 12 h x 14 d, then 3 mg / kg po q. 12 h x 28 d to start) all are potentially helpful choices.

Fluoxetine, an SSRI, has almost no effect on adrenaline, and, hence, potentially fewer side effects than do TCAs, but because it also changes the metabolism of the neuron through alterations in receptor conformation, it's impossible to be able assay efficacy for a minimum of 6–8 weeks.

Clomipramine is a TCA that is very similar to selective serotonin re-uptake inhibitors (SSRIs) like fluoxetine, except it does have effects on adrenaline, which is where many of the side effects come from. Clomipramine may be best suited for conditions primarily involving anxiety and ritualistic behaviors, whereas fluoxetine may be best suited for conditions involving reactivity and impulsivity.

As is true with humans, no one medication works for everyone and 3 or 4 medications or medication combinations may need to be tried before one that is successful is identified. Because of the amount of time needed to determine that a medication is a failure, this may mean 4–6 months of trying different medications or medication combinations. By playing the odds of the patterns discussed above, we may find which medication may work more quickly.

Lifelong maintenance medication may be necessary; some of these dogs may have a true deficit of serotonin or altered serotonin functioning in the same way diabetics can have a deficit of insulin. We generally ask clients to keep the dog on the drug for the amount of time it took to get the dog as perfect as possible, plus 30 d, and then wean the dog from the medication at the rate it took for the dog to improve. This translates to 4–6 months of treatment, minimally. If medication is long-term or life-long annual physical and laboratory evaluation are useful. There appear to be no side-effects long-term. Of course, this all assumes that client is also doing the relevant behavior modification. There are no quick fixes and indiscriminate use of drugs leads to treatment failures.

The most common, modern treatments for noise phobias involve drug treatment with medications designed to reduce or abort anxiety and panic. Most of the medications used are benzodiazepines. These drugs have some drawbacks including the potential induction of physiological dependence and the subsequent abuse that can follow. Dogs cannot open the bottles of medication by themselves so both of these are avoidable, but there are some households that should not have benzodiazepines present. If used rationally the benefits of this class of medication can be great and the risks few.

The drug of choice for most dogs is alprazolam. The optimal dose for most dogs who have any element of panic to their response is 0.02–0.04 mg / kg. For a medium sized dog starting with an initial 0.25 mg dose is rational. "As needed" is generally interpreted to be every 4–6 hours - the approximate half-life of many of the benzodiazepines.

The key to getting these medications to work is to get them into the dog before there are any behavioral, physical, or physiological signs of distress. For storm-related phobias clients need to learn what the trigger for their dog is because it may not be the noise, per se. Triggers can include flashes of light, noise, atmospheric pressure changes, ozone levels, et cetera. It may be good advice to recommend that the dog should be medicated if there is a 50% chance or greater of a storm and, or if the barometer is dropping.

Alprazolam lacks an intermediate metabolite found in diazepam and clorazepate that makes patients sleepy so it is a better choice for most dogs. If people need very long acting benzodiazepines, medications like clonazepam (0.5 mg / kg every 8–12 h; start low and work up as needed; in some dogs sub-clinical, very small amounts can have a huge effect), often used for some types of seizures and for sleep disorders, may be beneficial since it has a very long half-life.

References

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2.  Overall KL. Clinical Behavioral Medicine for Small Animals. St. Louis: Mosby, 1997:510–520.

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4.  Mojtabai R, Rieder RO. Limitations of the symptom-oriented approach to psychiatric research. Br J Psychiatry 1998;173:198–202.

5.  Nopoulos PC, Ceilley JW, Gailis EA, Andreasen NC. An MRI study of midbrain morphology in patients with schizophrenia: relationship to psychosis, neuroleptics, and cerebellar neural circuitry. Biol Psychiatry 2001;49:13–19.

6.  Spitzer H, Desimone R, Moran J. Increased attention enhances both behavioral and neuronal performance. Science 1988;240:338–340.

7.  Daniel H, Levenes C, Crépel F. Cellular mechanisms of cerebellar LTD. Trends Neurosci 1998;21:401–407.

8.  Salter MW. Src, N-methyl-D-aspartate (NMDA) receptors, and synaptic plasticity. Biochem Pharmacol 1998;56:789–798.

9.  Trotti D, Danboldt NC, Volterra A. Glutamate transporters are oxidant-vulnerable: a molecular link between oxidative and excitotoxic neurodegeneration. Trends Pharm Sci 1998;19:328–334.

10. Fones CSL, Pollack MH, Susswein L, Otto M. History of childhood attention deficit hyperactivity disorder (ADHD) features among adults with panic disorder. J Affective Dis 2000;58:99–106.

11. Lueger RJ, Lutz W, Howard KI. The predicted and observed course of psychotherapy for anxiety and mood disorders. J Nerv Ment Dis 2000;188:127–134.