Blue Dogs and Cats
Depression and Mood Medicines
An animal’s eyes have the power to speak a great language.
Many people are surprised when they ask me whether pet animals can experience depression, and I respond, “Yes, of course.” Depression certainly can and does occur in pets. A complex mental condition, depression is not a psychological state exclusive to humans. Naturally, because we are unable to communicate verbally with animals, we do not know as much about how depression manifests in animals as we do about how it affects people. For the same reason, the classification of depression in animals is somewhat imprecise. We can put a pet on a couch, so to speak, but our notes on the session won’t include any verbal replies. We can, however, verify that the same molecules of emotion are coursing through a pet as through a person.
One of the first cases of animal depression I ever saw involved a cat named Maxwell. A few weeks before visiting me, Max’s beloved housemate, a companion cat with whom he was closely bonded, had died. Max went into an extreme behavioral funk. He refused to eat, became morose, lost interest in all normal activities, and basically slept the day away. As a result, Maxwell lost a great deal of weight. His owner initially brought him into our veterinary hospital to see one of the doctors in the Internal Medicine Department, who diagnosed liver failure, an unfortunate and extremely serious consequence of rapid weight loss in felines. The Tufts vets brought Max into our intensive care unit, where he was hydrated with intravenous fluids and received state-of-the-art treatment for liver failure. Although such a condition usually carries a grave prognosis, we managed to pull Max through.
Fortunately for Max and his owner, the clinician was savvy enough to realize that the root cause of the problem was depression-related anorexia and referred them to me for advice on how to manage Max’s mood, as he was still depressed. In order to help lure him back into the fullness of life, the owner needed to give him even more caring attention, to generally enrich his home environment with interactive toys and games, and possibly adopt a new kitten to help make up for the loss of his dear friend. The mainstay of my treatment, however, was Elavil, an antidepressant commonly used for people. After a couple weeks, Maxwell was back on his feet, eating and living a normal life, although the owner did not take my advice to get a new kitten.
To me, Maxwell is a poster child—or poster cat—for how psychological issues can affect physical health and wellness. In psychiatry, this feline’s experience would be termed a major depressive incident. Some stern stoics believe that the blues can simply be shrugged off with strongmindedness. “It’s a question of character, damn it!” But Maxwell, the cat with the blues, shows that a creature can come close to dying from the physical repercussions of depression.
One of the several dogs I have seen with depression also developed the condition following the loss of a beloved housemate. Like Max, Oliver, a neutered mixed-breed pit bull, lost his appetite, became uninterested in toys and games, and generally lost interest in life. He moped around the house and slept for inordinate amounts of time.
I treated the dog in a similar way to the cat and recommended what we might call in the UK “jollying up” routines. I told the owners to act happy around Oliver, to jolly up Ollie, so to speak. High spirits can be as contagious as low ones. Plus I advised that they play with him a lot more, devise games, and give him attention, delicious food, walks, and other outdoor activities. I also advised the family to consider adding a new pet to their household.
In fairly short order, the owners did all of that. Though Ollie’s depression had prevailed for several weeks, upon arrival of a new puppy he began to turn around quickly. Soon Oliver was completely back to his old self. The new puppy, in this case, was just what the doctor ordered.
Another canine case had special, heartbreaking circumstances. The owners had tried to hide the death of one of their dogs from the surviving pet, who had been closely bonded with his housemate. The owners had had to euthanize the ill dog to prevent his increased suffering from a terminal disease. The wife took the healthy dog away from the house while the owner’s spouse, who had taken their sick dog to the vet for the sad procedure, brought the body back home and buried it in a deep grave in the backyard.
When the euthanized dog’s canine companion returned home, he ran around the house looking for his old friend, dashing from room to room. Eventually, he went outside and tore around the perimeter of the house in a state of panic. When he finally discovered the fresh grave, he lay on top of the dirt mound and would not budge for several days.
Examples of dogs who mourn their owners abound. One of the most famous stories is of a little Skye terrier in nineteenth-century Edinburgh, Scotland. Known forever after as Greyfriars Bobby, the dog faithfully guarded the grave of his owner for the last fourteen years of his life. A book and a movie have been devoted to that remarkable case as well as to that of the Akita, Hachiko, celebrated in Japan as a model of loyalty. Hachiko always saw off his owner at the train station and went back to meet him at the end of the day. When the owner failed to return one afternoon, having suffered a stroke and died while at work, Hachiko met the same train again and again for nine years, waiting for his owner’s return.
Clearly, most mourning dogs miss their dearly departed and suffer from a depressed mood. The condition is, for the most part, not life-threatening, and can probably be classed as minor depression, but it can last for quite some time.
Horses also feel depression as a result of bereavement. One of our own horses, Dolly, a chestnut-colored mare, showed signs of such depression. The love of her life was our other horse, Jack, a jet-black, 1,500-pound Cheval Canadian gelding with a flowing mane. Dolly adored Jack and Jack adored Dolly back. It was as if she only had eyes for him and he only had eyes for her. My wife and I had owned these two horses for many years. Jack once had a bout of colic but otherwise was in good shape. As they aged we became progressively more cognizant of the fact that they would not be around forever. Jack began to have arthritic issues and was almost always lame or sore on one foot or another. Corrective shoeing and a regimen of painkillers became the order of the day.
Jack was a proud and handsome beast. Dolly knew it and admired him for what he was. But one terrible day, when Jack was about twenty-five years old, he colicked again, this time much more seriously. My veterinarian wife, Linda, knows a fair bit about horses and recognized immediately that Jack needed an equine specialist vet, whom she summoned. The vet administered painkillers, performed a thorough examination, and took blood for analysis. Toward the end of that day, Linda was quite hopeful that he might turn a corner.
The next morning the phone rang early and we learned the awful news that Jack had cast himself on the barn floor and was thrashing around wildly. Linda hopped in her car and sped to the barn, calling the equine vet on the way. They arrived at the same time. They gave him more painkillers and another examination. The news was not good. Jack’s impacted large colon had now shifted horizontally across his abdominal cavity, a very bad sign.
Linda called to tell me that she was going to have Jack put down because he was in so much pain. Even with emergency surgery, his chances of survival were next to none. I tried to get her to bring Jack to Tufts Large Animal Hospital, but she knew I was grasping at straws. Jack was peacefully euthanized at the barn and buried.
For weeks after Jack’s death, Dolly moped around and was clearly not herself. She did not interact with the other horses when turned out to pasture but simply stood there, limp, listless, staring blankly at nothing in particular. Her stall was opposite Jack’s and so now she had only an empty space to look at. As soon as we saw that depressing situation we had another horse moved into Jack’s former stall. Dolly’s behavior hardly changed. It was another horse all right, but it wasn’t Jack.
A lot of people say to friends who have lost an animal, “Oh, don’t worry, you can always get another pet like Pookie.” But you can’t. Every animal is an individual, so substituting one for another is not something that instantly relieves the pain.
The same holds true for horses. After weeks of this low-ebb state, Dolly did come out of her funk and eventually got back to life as usual. But during her “mourning period,” it was plain—and painful—to see her suffering over losing Jack. Here was a clear demonstration of a secondary emotion in an animal: Dolly’s primary emotion of sadness led to such secondary emotions as suffering and loneliness. Since such a reality cannot be easily quantified, some people continue to deny that it occurs. But we saw our mare bereft and isolated, a solitary being standing apart in a pasture full of horses, missing the one horse who was her soul mate.
Other forms of depression in animals may be more subtle. Some house cats can become depressed when they lack exercise and the opportunity to engage in psychologically gratifying, species-typical behaviors. Cardinal signs of this type of depression are that the cat sleeps for hours a day, eats a lot, and is overweight. Overeating and weight gain, the antithesis of anorexia and weight loss, can also be signs of depression. It is absolutely not normal for house cats to sleep for 75–80 percent of the time. Nondepressed cats sleep for only around ten hours a day. When the period of sleep climbs higher than that, the behavior becomes abnormal and should be examined as a possible psychological problem. While depression may be too strong a term for this chronic state of affairs, behaviors like overeating and oversleeping are definitely cause for concern.
A better term to invoke here might be dysthymic disorder. In humans, the condition is characterized as “depressive-like symptoms” that are severe enough to interfere with normal functioning and well-being. The correct treatment for what might be called feline dysthymic disorder is somewhat counterintuitive.
I do not advise owners to allow cats outside the house. The outdoor environment is dangerous and life-threatening. Instead, I suggest owners provide their cat a good deal of indoor enrichment and entertainment, as well as encouraging daily exercise. A compatible feline companion cat can also help a morose, inactive, overweight cat by providing opportunities for social interaction and play, both of which can help chase the blues away.
When deprived of opportunities to interact and behave normally, dogs also may suffer from a chronic disorder of depressed or dysthymic mood. The classic example here is, once again, the brood bitch in a puppy mill. The typical subject spends a large percentage of her life crated. She has little opportunity to do anything except eat, drink, and lie down or stand up. Stress, isolation, and lack of social support are the order of the day for these pathetic creatures. In his former existence, when he was a twenty-three-hour-a-day prisoner in his own crate, my dog, Jasper, slept away his days.
Such dogs seem to exhibit what is called learned helplessness, which is representative of human depression. Their barren existence can lead to dysthymia or other stress-related conditions. Many dogs rescued from chain-link prisons arrive in a new home in a completely dysfunctional state. As mentioned previously, they do not bark, play, or wag their tails for many months after they are “sprung,” and appear socially anxious and generally fearful, although treatment and retraining, such as my wife and I gave our dog Jasper, can often help them recover.
A tragic variation on the theme of learned helplessness is evident in the story of a gorgeous English gun dog, who was accidentally locked in a pantry while his loving family was preparing to go on a long road trip. It was a bit like the movie Home Alone, when in the midst of a confused departure, a family takes off leaving their young son, well, home alone. The difference is that the true story had a much darker conclusion. When the family returned weeks later, they found their dog had starved to death.
The original plan was for the setter to have free entrance into the house and egress via a pet door to the yard, where he would have access to a self-feeder. Yet even in the pantry, the dog was surrounded by food. Game birds had been hung—within reach—to ripen and plastic bags full of food could have been easily ripped open.
When I first heard of this case, I concluded that the dog did not eat the food out of sheer obedience, having been trained not to touch the spoils. But now, years later, I believe the poor dog found himself alone in a hopeless situation. His reaction morphed from panic to helplessness to depression. He went into a state dog trainers call “shutdown.” This is seen occasionally during harsh leash training, when canines collapse into atonic immobility after receiving a barrage of inescapable “corrections.” Shutting down is really a kind of learned helplessness, a condition that is a dead ringer for—and used as a model of—depression.
This happens when there’s no way out. Whatever you do, whichever way you turn, nothing will change the terrible situation you find yourself in. Appetite is lost, motivation is lost, activity is reduced, numbness follows. Although this story had a terrible ending, it serves to show that dogs—and other animals—sequestered at home during long owner absences can become frankly depressed. And in such cases we can objectively prove the anguish that such animals feel, since research studies have turned up increased stress hormones in their blood. Eighty percent of dogs left home alone have increased cortisol levels, and cortisol is one of the stress markers in dogs and people.
The next time your sitter or the kennel owner tells you that your dog merely sleeps while you are away, think again. He may be depressed.
Psychiatrists have long argued over whether depressive personality disorder exists and whether it can set someone up for depression. A gloomy, dejected outlook, worry, and pessimism can predispose people to depression. I can think of animals that I have seen who have such a negative outlook on life, dogs in particular and horses, too. I’m not thinking of Droopy or Eeyore here, but actual animals that I have known. One owner actually brought me his dog because the dog appeared to him to be depressed all the time. There was no known precipitating cause for this dog’s gloomy outlook on life. The dog stood like a sawhorse in my consulting room and did—nothing. Facially, he had an unmistakable hangdog look. Nothing I could do at the time—showing him novel dog toys, offering him special treats, petting him—caused him to show any interest. I did my best to advise this owner how to proceed, providing his dog more exercise, environmental enrichment, special food, mano a mano benign training at home, and more social opportunities. The treatment advice barely worked for this dog and the owner did not want to pursue pharmacologic intervention, so we both had to accept the fact that this dog’s negative outlook on life was simply a result of his innate personality.
In humans, another personality trait that may predispose people to depression is neuroticism, which is characterized by anxiety, moodiness, worry, envy, and jealousy. Personally, I believe that certain personality traits in animals do predispose them to depressive tendencies, but nailing down what that is has proved an elusive goal. Yet, the canine purebred population represents a virtual genetic laboratory, one that rivals Gregor Mendel’s pea garden in potential usefulness to science. If such a predisposition toward depressive illness could be confirmed within certain breeds, then such populations of depression-sensitive dogs could help scientists searching for the genetic underpinnings of depression in people.
Depressed animals that I have seen do indeed seem to be more anxious and prone to worry than their more confident peers. I have not made a specific study of this subject, but my intuition and experience tell me that a dog who is morbidly attached to its owner or to another dog, or one that displays separation anxiety or other anxious conditions, may be more prone to dysthymic disorder or depression. That said, if environmental pressures are extreme enough, most animals, including humans, can be driven to depression.
In 2009, France’s former president, Jacques Chirac, and his constant Maltese terrier companion, Sumo, went through an acrimonious breakup. The dog had undergone treatment for depression after Chirac yielded the French presidency to Nicolas Sarkozy, and both pooch and owner were turned out of the Elysée Palace. The media questioned whether canines can indeed suffer from the condition, but it sure seemed as though Sumo wrestled with depression, so to speak. Whether from the abrupt change in surroundings or the lost election, the dog behaved lethargically and lost his appetite. He also became increasingly snappish. Accustomed to roaming free in the expansive gardens of the Elysée, the terrier found himself confined in an apartment on the Quai Voltaire. Luxurious as the new digs were, it was no palace. The formerly mellow Sumo bit the ex-president two times, causing serious enough wounds that Chirac required medical attention. Twice bitten, once shy. Chirac exiled Sumo to a farm owned by friends.
Sumo’s symptoms were eminently familiar to me: the lethargy, lack of appetite, the previously unseen edginess and aggression. At Tufts in the 1980s, decades before President Chirac lost his lovely terrier, I was at the Animal Behavior Clinic, and a colleague and I examined a dog with similar symptoms to Sumo’s—and who had also bitten its owner. I diagnosed depression and associated aggression.
A former colleague, who shall remain nameless, objected.
“Dogs don’t experience the same mental states and emotions that people do,” he said, repeating what back then was the party line.
“Well, how about this?” I answered. “Let’s give the dog an antidepression drug and see what happens.”
Of course, we know the outcome. Nowadays it is common for veterinarians to prescribe antidepressant drugs designed for people. The rising trend prompted Eli Lilly’s animal health division, Elanco, to introduce a chewable beef-flavored version of Prozac for use in dogs.
There’s an additional note to sound in the story of Sumo and Jacques Chirac, whose transition out of the French presidency in 2007 was not smooth. Soon after he left office, Chirac faced accusations of financial impropriety and was swept up in a series of official hearings, as he had lost the protection of executive immunity. This must have been extremely stressful—and pets reflect the moods, emotions, and personalities of their owners. The abrupt transition from palace to apartment might have been part of it, but Sumo’s awareness of Chirac’s distress no doubt contributed to the dog’s own upset. Once he was removed from that toxic emotional environment and placed on the farm in the beautiful French countryside, he never bit another person.
When I prescribe medicines for pets, I often hear this same response from clients: “But I thought that was a drug for humans, not animals!”
“Yes,” I reply. “But it works the same in animals.” I don’t point out to them that humans, after all, are animals themselves.
This conversation happens time and time again at our clinic at Tufts. Clients find it most odd when we send them to the local “human” pharmacy to pick up medications for their pets.
“You mean it’s exactly the same?”
“Yes, exactly the same.” A look of puzzlement and wonder crosses their faces.
If they but stopped a moment and thought about it, they might see how basic is the truth behind the practice. Evolution does not create creatures out of whole cloth. It builds upon what came before. The unity of all life, a concept so beloved by spiritualists, finds its expression in evolutionary biology. All mammals evolved from a mammalian prototype species. There was no need to invent an entirely new nervous systems, new limbic structures, new brain chemistries. What is now here was carried forward from the past.
A veterinarian friend of mine, Dr. Ian Glen, formerly my anesthesiology mentor at Glasgow University, left academia for the commercial world. He joined what was then Imperial Chemical Industries, or ICI, in England. His job was to screen scores of potential injectable or inhalational anesthetics for use in humans, using mice as a model.
One of the experimental, injectable anesthetics Dr. Glen worked on turned out to be exactly what ICI was looking for and later received its now well-known brand name, Propofol. The powerful anesthetic is used in hospitals around the world, but is notorious for being the pop star Michael Jackson’s preferred sleep aid. He called it “milk,” because that’s what it looks like when dissolved in a solubilizing agent for injection. Jackson overdosed and died after his personal physician injected him with it. “More milk,” were Michael Jackson’s last words.
Of course, any substance on the face of the earth can be abused. Propofol has benefited millions of surgery patients, largely without negative consequences. Punsters have labeled it “milk of amnesia,” a real-life version of “the enchanted stem” that puts the “brother mariners” of Ulysses into a trance.
Another acquaintance, Dr. Ross Terrell, developed an inhalation anesthetic, isoflurane, using similar rodent-based experiments. I was sitting next to him at dinner one night.
“Isoflurane has made your company, Anaquest, rich,” I said, an excellent opening gambit for any conversation. “Where did the company acquire it from? Who sold it to Anaquest?”
“We didn’t buy it,” Dr. Terrell replied. “I made it.”
Once again, as with Propofol, innovation flowed from laboratory animals directly to the human clinic. It’s the kind of thing that happens all the time.
All this arose from experiments first performed on mice. The concept behind my friend’s research—and the scientific research of millions of other experiments—is elegant in its simplicity: If it works in a mouse it will work in a person. Of course that would be true. Mice have a brain structure and a central operating system that are very similar to that of humans.
It could almost be called a foundational principle of pharmacology. What happens in animals predicts what will happen in people.
That pill you are placing in your mouth? A white lab rat has been there before you. It’s not just drugs for medical conditions, either. Pain medications and anesthetics follow the same path, as do psychoactive drugs for treatment of anxiety and depression. All begin on the drawing board and are then subjected to testing in rodent models before entering human clinical trials. If successful, human clinical trials lead to the licensing of that new drug for use in people. There are no intermediate steps. Like pharmacological boomerangs, some of the drugs then find their way back to use in animals.
Anxiety and aggression have been extensively researched using animals, and through these studies we’ve also learned about the neurochemical underpinnings of depression as well as how to treat it. As mentioned earlier, the neurotransmitter serotonin and its fluctuations are intimately involved in aggression. In humans and in other animals, serotonin levels fluctuate from dawn to dusk. So do moods, and so does the potential for aggressive responding. We all have a longer fuse in the morning and become more irritable in the late afternoon.
This fluctuation in serotonin levels participates in the so-called circadian rhythm of biological processes, their oscillation over a twenty-four-hour cycle. One other thing that affects the level of serotonin is what happens in the course of life. Certain accomplishments, such as winning a fight, increase serotonin. Defeat has the opposite effect. This result has been clearly demonstrated in monkeys. And, well, monkeys are us.
A serotonin experiment that teaches us a lot about ourselves was conducted with vervet monkeys and showed that dominant monkeys had higher serotonin levels than their subordinate cage mates. Dominance was actually associated with lower levels of aggression. Dominant monkeys did not have hair triggers. They didn’t need them! They knew they were ultimately in charge. They only responded with aggression when severely pressed.
In one experiment, the researchers removed the most dominant male monkey from the group. This left the others wondering who would be the new boss. A select few of the remaining male monkeys were treated with a serotonin-enhancing drug, Prozac. Those treated always achieved dominant status, became less aggressive, and engaged in more affiliative behaviors, such as mutual grooming. They also attracted more attention from the females.
The reverse was true, too. If the remaining male monkeys were treated with a serotonin antagonist, they always became subordinate, less social, and more aggressive. In other experiments in monkeys, low serotonin levels were shown to be associated with greater risk taking, including lashing out aggressively instead of considering the possible consequences of initiating an altercation.
We know that increasing serotonin decreases aggression. This holds across a range of species, from rodents to humans. Conversely, we know that decreasing serotonin darkens mood and creates impulsivity and aggression. We treat aggression in animals with drugs, but, while no drugs are approved to treat aggression in people, there are plenty of medications that are used off-label to do just that. One of these is clonidine, which works by decreasing the release of the catecholamine norepinephrine from nerve endings in the central nervous system. Its primary use in people is to control blood pressure. But psychiatrists also employ it to control mood.
Reducing the release of catecholamines induces a calmer state of mind. Clonidine finds application in treatment of attention deficit, hyperactivity, mood instability, and aggressiveness, particularly in children. At Tufts, we’ve long used clonidine as an effective therapy for fear-related aggression in dogs. If we had found that clonidine reduced aggression in dogs before psychiatrists discovered the effect in people, we could have predicted the cross-species antiaggressive applications in human medicine.
When you come to consider the big picture, without animal testing there would not have been any of the major drug developments over the last sixty-five years or so. One huge breakthrough during that period was the discovery of what became known as neuroleptic drugs, later grouped under the antipsychotic class of medicines. Even before its antipsychotic effect was noted, chlorpromazine was the first of these neuroleptic drugs to be studied in humans.
The term neuroleptic comes from the two Greek words: neuro, meaning nerve, and leptikos, meaning seizure. When chlorpromazine was first given to rodents, the creatures became instantly immobile. Chlorpromazine’s antipsychotic effect came from blocking dopamine in the brain. Modification of chlorpromazine led to the development of acepromazine, a tranquilizer used frequently by almost all veterinarians today. Its effect on animals is the same as chlorpromazine on people. ACP, or Ace, as acepromazine is colloquially referred to, calms and sedates agitated animals and is often employed as a preanesthetic, just like chlorpromazine in the original “lytic cocktail.”
The first antidepressant, imipramine, was termed a thymolytic, a term that roughly translates into “taking hold of the emotions.” In the late 1950s, imipramine was developed directly from chlorpromazine, primarily in an attempt to improve the drug’s effectiveness. From there, other antidepressants with the same tricyclic structure were fabricated. The age of psychopharmacology had arrived.
Researchers eventually determined that depression was related to low levels of serotonin in the brain. One of the effects of these early antidepressants was to boost serotonin levels. That realization led to the quest for selective serotonin reuptake inhibitors, the vaunted SSRI class of medicines.
Over the ensuing two decades, many SSRIs were developed. Some were more successful than others. Two of the first to be used were fluvoxamine, later marketed as Luvox in the United States, and citalopram, sold as Celexa.
Perhaps the most high profile SSRI of them all, fluoxetine, or Prozac, came on the US market in 1988. Of course, initial testing of Prozac’s serotonin reuptake properties occurred in the brains of laboratory rodents. Researchers with the Eli Lilly company, such as the scientist David T. Wong and the clinician Jong Sin-Horng, knew SSRIs would have the same effect in human brains. Intuitive, right? It was a no-brainer.
SSRIs are so popular in psychiatry that they are used more than any other class of drug. I once quizzed a professor of psychiatry at Harvard how commonly Prozac-like meds were used in his field.
“Eighty-five percent of the time?” I suggested.
“Oh, more than that,” he replied.
In human medicine, SSRIs are used to treat aggression, anxiety, phobias, PTSD, and obsessive compulsive disorder. I will allow you, the reader, who has by now been through almost the whole of this book, to guess which conditions they are used to treat in veterinary medicine. That’s right, the same ones.
Regarding human psychiatric drugs and veterinary behavioral drugs, the truth by now is well established. If it will work in animals, it will work in people. Conversely, if it works in people, it will work in animals. As Alexandre Dumas phrased it in The Three Musketeers, it’s a case of “One for all and all for one.”