Noise reactivities and phobias in dogs: Implementing effective drug therapy - DVM
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Noise reactivities and phobias in dogs: Implementing effective drug therapy
Dogs with noise phobias can benefit from drugs given before or during an anxiety-provoking event or even as lifelong daily drug therapy


DVM360 MAGAZINE


Stormy weather: Various drug interventions can help dogs better cope with storm and other noise phobias. (Eric Bean/Getty Images)
Last month, we defined noise phobias and looked at behavior medication tactics that can desensitize dogs to the offending noise—storms in particular. This month, we'll examine various drugs such as benzodiazepines, tricyclic antidepressants (TCAs) and selective serotonin-reuptake inhibitors (SSRIs) that can also help alleviate noise-induced anxiety.

Panicolytics

The most common and humane treatment for noise phobias involve drugs designed to reduce or terminate anxiety and panic. Most of the medications used are benzodiazepines, although medications that affect blood pressure (propranolol), heart rate (clonidine) and sleep cycles (melatonin) have also been suggested.

Benzodiazepines have one major drawback: They're controlled substances. In high dosages, especially for the drugs with longer half-lives, benzodiazepines can induce physiologic dependence, which means they should not be introduced into households with human substance-abuse problems. But if used rationally in a dog that has had a complete physiologic and laboratory evaluation that showed no abnormalities, the benefits of this drug class can be great and the risks few.

The list of medications commonly used to treat storm and noise phobias focuses primarily on benzodiazepines given orally:

  • Diazepam (0.5 to 2 mg/kg as needed)
  • Clorazepate (0.5 to 2 mg/kg as needed; use about 11.25 mg for a medium-sized dog; sustained-release forms are sometimes available)
  • Alprazolam (0.01 to 0.1 mg/kg as needed; best average dose is 0.02 to 0.04 mg/kg every four to six hours, as needed).

These medications are listed in order of duration—from longer- to shorter-action—of the parent compound. That said, no one wants a sedated or uncoordinated dog, and some of these medications (e.g., diazepam, clorazepate) are more likely to sedate dogs than are others (e.g., alprazolam).

Although diazepam and clorazepate have been commonly used to treat noise reactivity, the medication of choice in most dogs is alprazolam, in part because it does not use the N-desmethyldiazepam metabolic pathway. Any medication with N-desmethyldiazepam in its metabolic path can be sedating—an effect that's not desirable if using a medication frequently and hoping to avoid physiologic tolerance.

Alprazolam is not metabolized into N-desmethyldiazepam, so when it is given appropriately, it should not sedate the dog. The optimal dose of alprazolam for most dogs that have any element of panic to their response is 0.02 to 0.04 mg/kg. Because alprazolam comes in 0.25-, 0.5-, 1- and 2-mg tablets that are scored, it's easy to find a dose that works for most animals. For a medium-sized dog, starting with an initial 0.25-mg dose is best. As needed is generally interpreted to be every four to six hours, the approximate half-life of many benzodiazepines.

Alprazolam can be used as a preventive and as a panicolytic medication. To use it for prevention, the client must anticipate when there will be a provocative stimulus. Weather reports and Doppler radar can help. One choice for a medium-sized dog would be to give a 0.25-mg tablet one-and-a-half to two hours before the anticipated storm. Then repeat a full (0.25 mg in this example) or half dose 30 minutes before the event. Repeat every four to six hours as needed using either the half or full dose. Start with the half dose, as this dosing is cumulative.

To use alprazolam as a panicolytic, a full dose should be given immediately. If the dog is still distressed after 30 minutes, repeat with a half or whole dose. One of the terrific things about administering benzodiazepines is that they can be dissolved in a tiny amount of liquid or in a dog's cheeks.

Evaluating panicolytic dosing and response

Keep in mind with benzodiazepines that there's a huge amount of variation in response within any population, so adequate dosing becomes a matter of trial and error. Side effects can include serious sedation or paradoxic excitement. Clients don't want dogs so sleepy that they fall down stairs or drown in their water dishes—or so excited that they run through a glass door.

When clients are going to be home with their dogs for at least four hours, they should give their medium-sized or larger dogs at least 0.25 mg; small dogs should receive half that dose. If a dog is so sedated it cannot function or is uncoordinated (ataxic), this dose is too high. Halve the dose the next time it is administered. If the dog is still sedated, you may need to help the clients find another medication.

Clients can check for excitement using the dosing procedure just discussed. If the dog starts to pant and run around, or if it loses focus and seems wild-eyed, frantic, scared or otherwise agitated, the client should protect the dog and let the medication wear off. If the client wishes to try again, he or she should halve the dose. If the dog is still agitated, you should find another medication.

When a client is going to be home with a dog, he or she can dose the animal as discussed above. If there's no provocative stimulus, the dog should seem normal. It may sleep more deeply but should awaken on request and not seem at all sedated. That is, the client shouldn't be able to tell the animal was given medication, except that the dog may be hungrier than on days when the drug was not given.

To learn if a dose will help a dog, clients should follow these steps:

  • For a week, try the baseline dose.
  • If after that time there's still no effect, double the dose.
  • After another week, double the dose again.

If the dog is not large and is getting 2 to 4 mg and there's no effect, it's unlikely the dog will respond to this medication. It may, however, respond to other benzodiazepines alone or in combination with tricyclic antidepressants (TCAs) and selective serotonin-reuptake inhibitors (SSRIs) or an anticonvulsant medication such as gabapentin. The same pattern of dosage testing can be used with other drugs or drug combinations.

If you discover the dog responds to alprazolam but needs a longer-acting benzodiazepine, clonazepam (0.5 mg/kg every eight to 12 hours) may be beneficial, since it has a long half-life. Clonazepam is often used for some types of seizures and for sleep disorders. Dosing should start low and increase as needed; in some dogs, small amounts can have a huge effect.

The key to getting these medications to work is to give them to the dog before behavioral, physical or physiologic signs of distress develop. For storm-related phobias, clients must learn what the trigger is for the dog, because it may not be the noise per se. Triggers can include such things as light flashes, noise, atmospheric pressure changes or changes in ozone levels. Many weather programs can be downloaded to laptops or handheld devices and set to alert clients to certain atmospheric cues. Regardless of the dog's cue, the client must give the drug to the dog before the animal begins to react to the stimulus.

Benzodiazepines can be terrific medications, but they vary hugely in effect from one individual to the next. This lack of predictable effect is one reason benzodiazepines are not used as often as they once were.

Alternatively, numerous anecdotal reports seem to recommend melantonin or beta-blockers such as propranolol to treat noise reactivity. Without controlled studies, it's difficult to evaluate these claims or dosage ranges. An open-label trial of clonidine1 suggests this alpha-2 agonist, typically used as an antihypertensive agent in human medicine, may help in such situations. The recommended initial dose is 0.01 mg/kg once or twice a day orally, with an interdose interval of at least six hours. Stepwise increases up to 0.05 mg/kg or 0.9 mg/day have been used.

Maintenance medication

The goal of noise phobia treatment is not to sedate the dog but to stop its distress while helping the animal act as normal as possible. Medications can be used on an as-needed basis in addition to maintenance medications such as TCAs and SSRIs.

In fact, we now know that many dogs with separation anxiety also react to noises, and most animals that react to noises are at risk for developing other anxieties. If both of these or any other comorbid conditions are not treated, the dog's behavior won't improve.

For example, many dogs with separation anxiety will need a TCA or SSRI daily and alprazolam only if there's a storm. Meanwhile, others have a component of panic to their response to being left. In this case, the dog also will need alprazolam any time it's left, preferably before it begins to become distressed. This may mean that some dogs will need to be given alprazolam every time they experience an anxiety-inducing situation or stimulus. If the medication and dosage are helping the dog, that's great, but assessment is critical. For dogs that have concomitant anxieties or anxiety-related problems, or for those whose noise phobia is profound, maintenance medication designed to reduce the animal's overall reactivity and anxiety, and to raise the threshold for a reaction involving panic, is recommended.2 This means treating the dog daily with a TCA or SSRI.

Again, clients must be able to assess the dog to see if the medication is making it worse (e.g., more incidents, greater intensity), making it better (e.g., fewer incidents, lesser intensity) or having no effect. By keeping daily logs and routinely videotaping the dog, a client will be able to note changes in many anxiety-related behaviors, including destruction, elimination, self-mutilation and barking. Panting and more subtle behaviors may require that clients be present to observe.

Regardless, instruct the client to pick some subset of the behaviors the dog exhibits when distressed and monitor these for change. The information you and the client gain will help with management of the dog's medication.

Clearance of these medications is through liver (hepatic glucuronidation pathways) and kidney excretion, so knowing these pathways aren't impaired is important if we are to avoid side effects and minimize risk. Learn about the animal's ability to metabolize the drugs by taking a blood sample and looking at serum kidney and liver enzyme activities. All TCAs affect the reuptake of serotonin and norepinephrine, and the extent to which they do this for each catecholamine depends on the specific TCA. The desirable effect is the one associated with reuptake inhibition for serotonin; anxiety has been associated with low levels of serotonin. The SSRIs primarily affect serotonin, and most are relatively specific for one class of receptor, the 5HT1A subtype, thought to be involved in many anxiety-related conditions.

When considering the combined use of TCAs or SSRIs with benzodiazepines for dogs with two diagnoses or profound, daily noise reactivity, the first medication of choice may be amitriptyline (1 to 2 mg/kg orally every 12 hours for 30 days to start) because it's inexpensive and nonspecific and will show an effect within a month. However, amitriptyline's lack of specificity for certain receptors means it's often not the best medication by itself unless the problem started recently.

If amitriptyline fails to provide appropriate relief, or if the dog is severely affected or has been affected for some time, more specific medications may help. Fluoxetine (Reconcile—Eli Lilly;1 mg/kg orally once a day for eight weeks to start) is an SSRI. It has almost no effect on adrenaline and, hence, potentially fewer side effects than TCAs. But because it also changes the metabolism of the neuron through alterations in receptor conformation, it's impossible to evaluate efficacy for a minimum of six to eight weeks.

Clomipramine (Clomicalm—Novartis; 1 mg/kg orally t.i.d. for 14 days, then 2 mg/kg t.i.d. for 14 days, then 3 mg/kg t.i.d. for 28 days to start) is a TCA that's similar to SSRIs such as fluoxetine, except it does have effects on adrenaline, which is where many of the side effects come from. Clomipramine is best suited for conditions primarily involving anxiety and ritualistic behaviors, whereas fluoxetine may be best suited for conditions involving reactivity and impulsivity.

Another medication that can be considered is sertraline (1+ mg/kg orally either once or twice per day). This human SSRI has been used in dogs to treat a variety of behavior-related conditions including anxiety and obsessive-compulsive behaviors. Its limited use in dogs makes it difficult to compare to other SSRIs.

Drug administration during a panic attack

Finally, there's even some benefit to giving a benzodiazepine to a dog after it has already reacted. This won't abort the attack but may shorten it and scramble some short-term memory about how terrible the experience was. Alprazolam is truly panicolytic, that is, it cuts through panic and can and should be given during a storm or panic attack. It's important to remember that we all learn to panic or become anxious the more often it happens, so the humane thing to do is use medication every time it's needed.

Finding the right regimen

As is true in people, no one medication works for everyone, and three or four medications or drug combinations may need to be tried before one is successful. Unfortunately, because of the amount of time needed to determine that, it may mean four to six months of trial and error. By considering the behavior patterns of the individual dog, it may be possible to find which medication works more quickly.

Lifelong maintenance medication may be necessary; some of these animals may have a true deficit of serotonin or an altered serotonin, functioning in the same way diabetics can have a deficit of insulin. We generally ask clients to keep giving their dogs the drug for the amount of time it takes to get the dog as "perfect" as possible, plus 30 days. Then we wean the dog from the medication at the rate it took for the dog to improve. This translates to four to six months of treatment, minimally. If medication is long-term or lifelong, annual physical and laboratory evaluations are useful. There appear to be no side effects long-term. Of course, this all assumes that the client is also doing the relevant behavior modification. As noted previously, there are no quick fixes, and indiscriminate use of drugs leads to treatment failures.

Summary

Storm and noise phobias are common, debilitating and run in family lines. Without treatment, they worsen quickly and may make dogs more prone to other anxiety-related conditions. Noise and storm phobias are true welfare and quality-of-life issues and should be viewed as emergencies because of their comorbidity component.

Treating noise- and storm-phobic dogs with medication before the expected provocative stimulus—especially when combined with general behavior modification designed to teach the dog to relax while avoiding inadvertent reassurance of abnormal and undesirable behaviors—can be successful. As with most problems involving panic and anxiety, the earlier we can intervene, the greater the chance of success.

Also remember this condition will require a degree of management, including anticipating when the dog is likely to be exposed to a scary noise and protecting the animal while it continues to improve. For some dogs, treatment is lifelong, while for others it will be short-term. Once present, phobias are extremely difficult to completely obliterate because the memory of a phobic response can trigger another one.

In reality, it doesn't matter if the dog always has the potential to react throughout its life if we can alleviate the distress the dog feels whenever the noises that scare it occur. For most dogs, we can now alleviate the fear and panic experienced during a noise-phobic event, and that's a good place to start.

Dr. Overall, faculty member at the University of Pennsylvania, has given hundreds of presentations on behavioral medicine. She is a diplomate of the American College of Veterinary Behavior (ACVB) and is board-certified by the Animal Behavior Society (ABS) as an Applied Animal Behaviorist.

REFERENCES

1. Ogata N, Dodman N. The use of clonidine in the treatment of fear-based behavior problems in dogs: an open trial. J Vet Behav Clin Appl Res 2011;6:in press.

2. Crowell-Davis SL, Seibert LM, Sung W, et al. Use of clomipramine, alprazolam, and behavior modification for treatment of storm phobia in dogs. J Am Vet Med Assoc 2001;222(6):744-748.

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Source: DVM360 MAGAZINE,
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