Understanding Behavior-Altering Drugs For Dogs

By Mary Straus

Ten years ago, my dog Piglet woke me in the middle of the night, trembling violently and utterly terrified. It took me hours to track the source of her panic to a barely audible high-pitched beep that sounded once every two minutes, coming from a smoke alarm’s low battery indicator.

Thus began Piglet’s long history of noise phobias. Below is the story of my struggle to help her cope with these phobias and, eventually, generalized anxiety disorder. While I would urge anyone dealing with anxiety issues to first try natural methods of treatment, it is important to know there are medications that can offer your dog quality of life that may not be obtainable in any other way.

A brief history
For years, Piglet reacted only to high-pitched beeping noises, such as cell phones, pagers, the microwave oven, the theme from The Twilight Zone, etc. I tried many natural treatments, including T-Touch, an Anxiety Wrap, melatonin, flower remedies, dog appeasing pheromone (DAP) diffusers, counter-conditioning (scary noise = treat), and just about everything else I heard of that can help dogs with anxiety and phobias. Several of these helped a little, but none solved the problem. We dealt with her issues mostly by trying to avoid “scary noises,” including giving up some of my favorite TV shows!

Piglet was normally a confident dog, cautious with people but not fearful, comfortable with other dogs, eager to explore new places. When she was frightened by beeping sounds, she would pant, pace, tremble, try to hide, dig compulsively both indoors and out (to the point of making her nails bleed), and come to me for attention and comfort, though comforting her did not help. I knew enough not to reinforce her attention-seeking behaviors, but I did try various things, such as distracting her with clicker training (which would work only as long as I could keep it up, then she would go right back to her fearful behaviors), giving long, slow strokes, just putting my arm around her, sitting with her while completely ignoring her; nothing made any difference.

As we could avoid “scary noises” most of the time, her anxiety attacks were not frequent and she was able to live with her phobias pretty well.

This began to change three years ago, when my next-door neighbors completely rebuilt their house. We were out for a walk one day, soon after construction had started, when a stump digger close to us backfired loudly just as we were passing. After that, Piglet became reactive to all of the construction sounds from next door, which gradually generalized to any loud noise she heard while on our walks.

Sounds that had never before bothered her, such as lawnmowers, leaf blowers, loud trucks, and even the sound of other dogs barking, now frightened her. Most of our walks were spent trying to avoid these noises, and when she did hear them, she wanted to turn around and go home.

Eventually, Piglet was startled on a walk by a loud chirping noise from a ground squirrel. After that, she began waking at dawn, reacting to the sound of birds in my yard. Soon she was spending most of the night awake, pacing, panting, unable to rest and pawing at me to get up as well. Her noise phobias had escalated to generalized anxiety disorder (GAD). Neither of us could live like this. We had to find something to help.

Types of anxiety medications
There are several types of anti-anxiety medications (anxiolytics). Benzodiazepines are fast-acting and can be used on an as-needed basis, or combined with longer-acting drugs for a quicker response and when a little more help is needed. Tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and azapirones must be given continuously, and require several weeks to reach full effectiveness. Dogs with frequent or severe anxiety will benefit from these longer-acting drugs to decrease overall anxiety and reactivity.

All of these are prescription medications. It is important that you work closely with your veterinarian, or with a veterinary behaviorist, when using anxiolytic drugs. It is also important to do behavior modification as well, as drugs alone will rarely resolve a severe anxiety problem by themselves, just as behavior modification alone often will not work without drugs. A dog behaviorist (veterinary or otherwise) can help you with this.

Following is a summary of the different types of anti-anxiety drugs, what they are commonly used for, and what you need to know before using them. With the exception of clomipramine, the FDA has not approved the use of these drugs in dogs, as the drug companies have not submitted the necessary research. However, many of these drugs were tested on animals before use in humans, and they have been used off-label by many vets.

I’ve found Plumb’s Veterinary Drug Handbook to have the most current information on drug dosages and interactions. Some of the following is taken from that source, and some from various papers written by noted veterinary behaviorist Dr. Karen Overall and other veterinarians.

Benzodiazepines (BZs)
Benzodiazepines are fast-acting drugs that can be used on an as-needed basis for dogs that need periodic help with anxiety, such as those afraid of thunder or fireworks. They can also be used in combination with TCAs or SSRIs when first starting treatment to hasten the effects, or on an ongoing basis, either regularly or as needed to prevent or lessen acute anxiety episodes. For example, one might use a benzodiazepine with tricyclic antidepressants for a dog suffering from separation anxiety with a panic component.

The effects of BZs do not last very long, usually only a few hours. When used continuously, they are addictive (create physical dependency).

Benzodiazepines commonly used with dogs include alprazolam (Xanax), clonazepam (Klonopin), and diazepam (Valium). These drugs are used to treat anxiety, noise phobias (including thunder phobia), panic attacks, and separation anxiety. They should be used with caution in fear-aggressive dogs, as they may lower fear-based inhibition and increase the likelihood of the dog biting.

Their safety range is very wide, and they can be combined with most other medications, including TCAs and SSRIs, as well as with pain medications such as tramadol. They can also be used together (with dosage of each reduced). As with all anti-anxiety medications, you should start with a low dose and increase only as needed. “The key to treatment for noise phobias and panic is to give the benzodiazepines early and often,” says Dr. Overall.

Alprazolam is Dr. Overall’s drug of choice for dogs with storm and noise phobias and dogs who panic. It takes effect very quickly, within 20 minutes of being given, and does not tend to cause sedation. Alprazolam has some effect if given after the dog becomes anxious, but it works far better if given ahead of time. For dogs with thunder phobia, it should be given whenever a storm is expected, rather than waiting until it arrives, though more can be given at that time, if needed. The recommended dosage range is quite wide, with the highest dose being 10 times the lowest dose.

Clonazepam is used less frequently than alprazolam, as it takes a little longer to be effective, but it is also longer-lasting. There are two recommended dosage levels for clonazepam: one for seizure control, and one for anxiety. It is important to be aware of this, as the dosage for seizure control is much higher than that used for anxiety. I was reassured to realize how high a dose could be given without being dangerous.

Diazepam is more sedating than the other drugs in this class, and may have less anxiolytic effect, so it is generally not recommended for anxiety. It is the shortest-acting of this drug class in dogs, and does not take effect as quickly.

In Piglet’s case, benzodiazepines were a lifesaver. I found an article by Dr. Overall that discussed the use of alprazolam for noise phobias (see “References” sidebar). I started Piglet at 0.25 mg (0.017 mg/kg), but that had little effect, so I went to 0.50 mg (0.03 mg/kg), which did help. I started by giving Piglet this dosage of alprazolam whenever she would wake me up, which was generally a couple of hours after we went to sleep. She would usually settle down within an hour after getting the medication. It helped, but wasn’t enough.

My vet then suggested that I give an increased dosage of alprazolam at bedtime, before Piglet became anxious. Rather than giving her 0.5 mg (barely enough to help) after she had awakened me with her anxious behavior, I began giving her 1 mg (0.07 mg/kg) at bedtime. This made a huge difference. The alprazolam did not sedate Piglet; it just relaxed her enough to be able to sleep, without anxiety waking her up during the night. By giving it to her before she became anxious, she was able to sleep through most of the night.

After consulting with a veterinary behaviorist, I started giving Piglet 1 mg alprazolam every eight hours, to try to prevent her from becoming anxious. Her anxiety was under control, but she seemed to be on something of a roller coaster, becoming more reactive each hour after the alprazolam was given. I generally had to get up once during the night to give her a dose, as it was too short-acting for her to be able to make it all the way through the night without waking and becoming anxious.

I decided to switch to clonazepam, as its effects last longer. Because the recommended dosage range of clonazepam for anxiety in dogs is similar to that for alprazolam, I tried giving Piglet the same dosage (1 mg), but quickly found out that was not enough. I increased the dosage to 2 mg (0.13 mg/kg), still well within the recommended range. I gave this amount twice a day, at bedtime and after breakfast. With clonazepam, Piglet was able to sleep through the whole night.

Azapirones
There is only one drug in this class used with dogs: buspirone (BuSpar). Buspirone is used to treat cats for inappropriate urination, but is now also being used to treat dogs for phobias and other anxiety disorders, including fear aggression, especially if accompanied by signs of poor socialization. It is not helpful for panic disorders, but is effective for more generalized anxiety.

Because buspirone has few side effects and does not cause sedation, it is an excellent first choice for treating dogs with aggression or anxiety that is not too severe. It must be given continuously for at least four to six weeks in order to determine whether or not it will help. Again, it’s best to start at a low dose and increase if needed. Buspirone can be combined with TCAs or SSRIs, though it is questionable whether this helps or not.

I learned about buspirone from Amy Cook, a dog trainer in Oakland, California, who has a special interest in fearful dogs. Amy has dealt with fear and anxiety in many dogs, including two of her own, and has learned a lot about the medications used for treatment.

Buspirone helped a number of Amy’s clients, as well as the dog of a colleague that had developed noise phobias and was unable to continue her flyball participation because of it. That dog responded wonderfully to Buspirone and was able to return to her flyball team with the help of this medication.

We started Piglet on a low dose (10 mg, or 0.7 mg/kg) twice a day for a month, and then increased to 15 mg (1 mg/kg) twice a day for another month. Unfortunately, it did not help, and I weaned her off it.

Tricyclic antidepressants (TCAs)
Tricyclic antidepressants are used with dogs to treat anxiety, panic, phobias, and obsessive compulsive disorders, such as shadow chasing and lick granulomas. They are also used to treat aggression that is caused by underlying anxiety.

The tricyclic antidepressants most commonly used with dogs are amitriptyline (Elavil) and clomipramine (Clomicalm). The general recommendation is to start with a low dose, then increase every two weeks as needed. These drugs do not take effect immediately, and several weeks’ treatment may be needed before their effectiveness can be fully ascertained.

The most common side effect of TCAs is sedation. Anorexia (loss of appetite) is also common, but usually goes away after a few days. Giving with food and dividing the dosage between meals may decrease gastric side effects.

My own vet prefers to use amitriptyline as a first choice when treating anxiety, not because it’s the most effective drug, but because it is inexpensive and he feels it is safer than clomipramine.

Amitriptyline’s most common side effects are dry mouth and sedation. It is well suited to dogs with relatively mild anxiety disorders, including anxiety-related aggression and submissive urination. It is not useful for compulsive disorders.

Amitriptyline can relieve chronic pain, and also has some action as an antihistamine.

Clomipramine is best suited for situations involving anxiety, including separation anxiety, as opposed to reactivity. Clomi-pramine is also very effective at treating compulsive disorders.

TCAs can cause bone marrow suppression. It’s important to do blood work a couple of weeks after starting this drug (as well as before, for older dogs), then monitor every six months to a year thereafter.

I tried giving Piglet amitriptyline for her noise phobia before she developed generalized anxiety disorder. With my veterinarian’s guidance, I started Piglet on 25 mg (1.7 mg/kg) twice a day, then increased it to a very high dosage of 25 mg three times a day after a month.

Piglet tolerated the drug very well, and she did not have problems with sedation or other side effects. However, as time went on, I noticed no improvement in her behavior, even after we increased the dose, so I weaned her off it.

After Piglet’s anxiety worsened, my vet and I decided to try clomipramine (Clomi-calm). We started at 20 mg (1.3 mg/kg) twice a day. After two weeks, I increased to 25 mg (1.7 mg/kg) twice a day. Again, Piglet tolerated it well; she had no stomach upset, and her blood work was normal after two weeks. She was on clomipramine for a total of only three weeks before I began weaning her off, as I did not feel it was helping, but in retrospect, I realize that she got much worse when I weaned her off the drug. It is very important not to give up too soon when giving TCAs or SSRIs.

Selective serotonin reuptake inhibitors (SSRIs)
SSRIs are antidepressants and anxiolytics, used to treat aggression, separation anxiety, generalized anxiety, panic disorders, and obsessive-compulsive behaviors. SSRIs are stronger, more effective, and longer-acting than TCAs, and may take longer to fully assess their effects. They are considered safer than TCAs, but they can have side effects, including gastric upset and sedation.

It is important to do blood work before starting, especially for older dogs, and monitor periodically after that. SSRIs can be combined with TCAs using low-end doses of each, which may help them take effect faster and lessen the chances of side effects.

Fluoxetine (Prozac) is the most commonly used SSRI with dogs, and has the longest half-life in people. Others include sertraline (Zoloft) and paroxetine (Paxil), all with similar potential side effects, though paroxetine is more difficult to wean off and may have a shorter half-life, leading to more variation in its effects.

The usual methodology is to start with a low dosage, and then increase if no improvement is seen after three to four weeks. Treatment must continue for at least six to eight weeks before you can know for sure whether it helps.

Fluoxetine is used to treat aggression, obsessive-compulsive disorders, separation anxiety, and panic and avoidance disorders, including post-traumatic stress disorder. Fluoxetine works well for conditions involving reactivity, including some forms of aggression. Paroxetine is used to treat depression, social anxiety, and agitation associated with depression. Sertraline is useful particularly for generalized anxiety and panic disorder.

After consulting with the veterinary behaviorist, we started Piglet on fluoxetine, at a low dose of 10 mg (0.7 mg/kg) once a day, and then increased to 15 mg (1 mg/kg) after two weeks.

Piglet did have some loss of appetite with this medication. Fortunately, after about a week, this problem went away. It also seemed to sedate her for the first couple of days, but she was normal after that. Her blood work was fine when we rechecked it a couple of weeks after starting the drug.

The fluoxetine helped, but I still felt that she was on edge and overly reactive.

I decided to make one further change and switch her to sertraline instead of fluoxetine. Sertraline is long-acting, similar to fluoxetine, which is desirable. I did discover that it is much more expensive, as there was no generic available (a generic version is expected to be released sometime in 2006). We started Piglet on a once-a-day dose of 25 mg (1.67 mg/kg).

Other factors influencing anxiety: chronic pain
Shortly after switching her to sertraline, Piglet underwent surgery to remove a broken carnassial (the largest tooth in the mouth), as well as a small tumor I had discovered between her toes. Because many medications can be dangerous to combine with SSRIs or TCAs, I had to be careful what pain medication was used.

I wanted to use tramadol, an effective prescription pain reliever, but had seen warnings about combining it with SSRIs, due to the risk of serotonin syndrome, though I later learned that this could be done with caution.

Instead, my vet suggested using Buprenex (buprenorphine), which is put into the cheek pouch and absorbed through the mucosal membranes (this works very well with cats; they don’t really know how well it works for dogs).

After she recovered from surgery, Piglet’s anxiety level reduced. In fact, she became almost normal again. I believe that she must have been experiencing some chronic pain that lowered her anxiety threshold. Although I know for certain that the tooth had just broken, it’s possible it was cracked and painful for a while before it was removed; she had stopped being an avid chewer some time before that, although my vet could find nothing wrong with her teeth. I also think that the small tumor in her foot may have been bothering her for a long time, though I was unaware of it.

For the next few months after the surgery, Piglet did not have a single anxiety attack. She had a few minor episodes, where she became restless, with some pacing and attention-seeking behaviors, but no panting, trying to hide, waking me up at night, etc. These episodes did not last very long, usually only about 20 to 30 minutes, before she was able to settle down again. At this time, I was giving her sertraline (25 mg once a day) and clonazepam (2 mg, twice a day).

Setback
Suddenly, Piglet became progressively worse over several days, culminating in a full-blown anxiety attack; I don’t know what caused it. I first suspected a defective batch of clonazepam, which I had just refilled, but when I switched to the name-brand Klonopin, she continued to have problems.

I spent another couple of months trying different things. I took her off Metacam (a prescription arthritis pain reliever), thinking that it might be upsetting her stomach, but that didn’t help. I put her back on Metacam and added tramadol, in case pain was still contributing to her anxiety, but that also did not help. She was not as bad as she had been originally, but she was still having full-blown anxiety attacks periodically, and was on edge most of the time.

After discussion with my veterinarian and veterinary behaviorist, we increased Piglet’s clonazepam to 3 mg (0.2 mg/kg), on the high end of the range for anxiety, but still well below the dosage used for seizures. This helped some, but not enough.

I finally decided to increase her SSRIs, though both my vet and the veterinary behaviorist were concerned with this. Because fluoxetine (Prozac) is considered to be two-and-a-half times as effective as sertraline (Zoloft) at the same dosage level in humans, but the dosage ranges given for dogs are similar, I twice tried to switch Piglet from sertraline to fluoxetine, but both times she got much worse and I switched her back. I then increased her sertraline dosage from 25 mg to 37.5 mg (2.5 mg/kg) once a day. Within a few days, she was back to normal.

That was over three months ago, and she has continued to do great since. On the rare occasion that she starts showing signs of anxiety, or if I have to leave her alone for too long, I give her melatonin (3 mg) plus a very small dose of alprazolam (0.25 mg). I am in the process of very slowly reducing her clonazepam dosage (it is addictive, so I am making only small changes every two weeks), and she is continuing to do well with the reduced dosage.

Don’t stop too soon
In hindsight, I believe that the SSRIs (fluoxetine and sertraline) and the TCAs (particularly clomipramine) helped more than I realized at first. Because they must be given for a few weeks before they reach full effectiveness, and because Piglet needed the addition of benzodiazepines, which are quicker-acting, I discounted the effect of the other medications.

I no longer question the impact of these slower-acting drugs. I would encourage anyone who tries TCAs, SSRIs, or buspirone to not give up too soon, keep using them for at least one to two months and preferably longer, before deciding that they’re not working and trying something else. If needed, you can combine them with the quicker-acting benzodiazepines to get some relief while waiting for the other drugs to take effect.

Piglet enjoys her walks and explores new places again, and no longer avoids areas where she might hear loud noises. Although they still disturb her a little, she doesn’t try to head for home when she hears them. She sleeps through the night peacefully and is relaxed during the day, even playful again. She is more interested in everything. It’s a small miracle, at her age (she is now 14), to see such improvement.

Although only the benzodiazepines are physically addictive, it is important to wean off all anti-anxiety medications slowly, reducing dosage gradually every one to two weeks, rather than stopping abruptly. Stopping SSRIs and TCAs too quickly can result in symptoms returning. Stopping benzodiazepines too quickly can lead to seizures; they must be weaned slowly as they create physical dependence.

Final (I hope!) notes
Piglet’s current drug regimen consists of sertraline (37.5 mg/day) and clonazepam (2 mg twice a day, and decreasing).

I have learned that when you find medications that work, you need to continue to give them for some time. A dog must be treated with SSRIs or TCAs for a minimum of three to five weeks before you are able to assess the effects; then, you must maintain treatment until all the dog’s symptoms are gone or are at the same low, consistent level, for at least another one to two months. Treatment should be continued after that for at least as long as it took to achieve that level, before even beginning to think about weaning them off. Total length of treatment should be a minimum of four to six months.

One of the mistakes I made was always trying to give the minimal drugs possible; every time I would see improvement, I would try to reduce the amount of drugs she was getting, and then she would get worse again. I have learned that it takes time to overcome anxiety disorders; they do not go away overnight.

If needed, I am prepared to keep Piglet on these drugs for the rest of her life. She is tolerating them well, with no side effects and continued normal blood work, and the improvement in her quality of life is so dramatic that I no longer fear having her on them. I have come to realize that there is no harm in relying on drugs when they are needed.

In hindsight, I wish I had tried using alprazolam for our walks when Piglet’s reaction to outside noises first escalated; I think she would not have gotten so bad if I had treated the problem early. I would never recommend anxiety drugs as a first choice, before trying to address anxiety with natural methods, but when a dog’s quality of life is at stake, the drugs can perform miracles. They have given Piglet back her life, and for that I am grateful.

-Mary Straus does research on canine health and nutrition topics as an avocation. She is the owner of the www.DogAware.com website. She lives in the San Francisco Bay Area with Piglet.