Het Placebo-effect verschijnt zelfs bij huisdieren

In 2003, a team of researchers from several American universities launched a small clinical trial, the results of which should not have been a surprise. Of the patients taking the active drug, an anticonvulsant intended to reduce epileptic seizures, 86 percent saw their seizure frequency fall. So did 79 percent of the patients that received a sham treatment, or a placebo.

It seemed like a classic example of the placebo effect, with one notable difference: The patients were dogs.

“As I did these placebo-controlled studies and I was evaluating data, I was like, ‘Oh, look, these dogs are getting better on the placebo,’” says Karen Munana, a veterinary neurologist at North Carolina State University who co-authored the study. That response had never been reported for epilepsy treatments in dogs before, she says.

At the time, double-blind placebo-controlled trials—the gold standard for evaluating new medical treatments—were relatively uncommon in veterinary medicine. But if Munana and her colleagues hadn’t done one, they would have misjudged how well the drug, levetiracetam, worked. “If I had not had the placebo arm [of the study], I would’ve said that this drug was effective,” she says.

While the placebo effect is a well-established phenomenon in human patients, it’s an underappreciated one in veterinary medicine. And the particular way it plays out in veterinary care highlights how unconscious cognitive biases can mislead humans when we care for other species. Even when pet owners are determined to provide first-rate care for the animals they love, these blind spots can undermine their best efforts. “The stories that we tell about our pets often aren’t really reflecting what’s happening to their bodies,” says Brennen McKenzie, a veterinarian and the author of SkeptVet, a blog dedicated to evidence-based veterinary medicine.

Doctors have long observed that mock medical treatments, such as sugar pills and saline injections, make many sick people feel better. Scientists believe that these improvements can be partly explained by the power of expectations; truly believing that a pill will alleviate pain or nausea, for instance, may in fact make that discomfort subside. Though much remains mysterious about animal minds, it seems unlikely that pets are bringing these kinds of beliefs into the veterinary clinic. “I don’t think our patients have an idea about their disease that we can affect by saying, ‘Here’s a therapy that can make you feel better,’” McKenzie says. And yet a number of studies—of cats, dogs, and horses—have found that dummy drugs seem to help ailing animals get back on their furry feet.

A variety of mechanisms could explain these observations, some of which might also play a role in the human placebo response. One possibility is simple regression to the mean—the animals could be getting better independently of any medical intervention. Chronic diseases such as epilepsy tend to wax and wane, and pet owners might be more likely to enroll their dogs in a clinical trial or try new treatments when the seizures are particularly bad. In many of those cases, the seizures might be bound to improve on their own, simply as part of the natural course of the disease.

Read: Autism’s placebo problem

Studies also show that people often change their behavior when they know they’re being observed. This so-called Hawthorne effect could help explain Munana’s findings. All the dogs in her study were on at least one anti-seizure medication in addition to levetiracetam, and pet owners might be more diligent about adhering to these drug regimens when their dogs are enrolled in a trial.

“Because they are in a study—and the owners know that their dogs are being scrutinized and the records are being scrutinized—maybe they’re more likely to give the medications on a more regular basis,” Munana says.

Animals in clinical trials might also receive better, more attentive veterinary care than they otherwise would. Some evidence suggests that gentle contact with humans may itself be therapeutic for certain creatures, including dogs and horses. And in some instances, classical conditioning could be at work. For example, rats that have regularly been getting insulin injections will still experience blood-sugar changes if they suddenly start receiving saline injections instead.

But in many cases, the most likely explanation is what’s known as the “caregiver placebo effect,” or “placebo effect by proxy.” In veterinary medicine, patients can’t speak for themselves. They can’t tell their doctors where they hurt—or even if they do. Instead, veterinarians have to rely on their own observations and judgments, as well as those of the animals’ owners, to infer how their patients are faring.

In many studies of canine epilepsy, including Munana’s, researchers depend on the dogs’ owners to keep track of the animals’ seizures. In most cases, it’s obvious when a dog is seizing, but sometimes owners have to make sense of more ambiguous signs and symptoms. For instance, some dogs drool when they seize, and an owner who discovers a spot of saliva on the floor has to decide whether it’s evidence of an unobserved seizure. Owners who believe that their dogs are on an effective treatment regimen may be less likely to come to that conclusion.

So it’s not pets that placebos are fooling, but humans. “When you give a treatment, there’s an expectation that the treatment’s going to be beneficial, and there’s a desire that my patient or my pet gets better—you want that to happen,” says Michael Conzemius, a veterinary surgeon at the University of Minnesota. The caregiver placebo effect, which has also been observed in studies of children, illustrates how unconscious expectations and desires can be deceptive, even for invested onlookers. And it could lead caregivers to perceive improvements in their pets’ health that don’t line up with objective reality.

Read: A journey into the animal mind

In one FDA-approved trial of an anti-inflammatory for dogs with arthritis, researchers used both subjective and objective measures to evaluate the dogs’ limb function. In addition to asking pet owners and veterinarians to assess the dogs’ degree of lameness at regular intervals over the course of the study, they also used force platforms to determine how much weight the dogs were putting on each limb as they walked; if a dog begins to put more weight on an arthritic leg, it’s a sign that the pup’s pain has diminished.

When Conzemius took a close look at the dogs in the placebo group, he found that owners and veterinarians frequently reported that the animals had improved, even when the gait analysis suggested otherwise. “Even if we both agree that the patient’s better, we’re not the patient,” he says. “So we have to be willing to set our opinions aside and actually look at other data, hopefully objective data, when it’s available.”

The desire to see pets improve can be so strong that it blinds people to the animals’ discomfort. McKenzie recalls seeing a rottweiler with osteosarcoma, a cancer of the bone, in one of his legs. It was clear to McKenzie that the dog was in profound pain—he wouldn’t put his paw on the ground and whimpered when the vet touched it. But when he offered to prescribe a painkiller, the dog’s owner demurred. She said she was treating her dog with homeopathic pain remedies, and she was sure that they were working. “She was absolutely convinced that her dog was not in pain,” says McKenzie, who is also the author of a new book on the evidence, or lack thereof, behind alternative veterinary remedies.

Indeed, that’s what makes the caregiver placebo effect so pernicious. Even though the treatments are inert, the traditional placebo response does in fact make patients themselves feel better. The caregiver placebo effect, however, simply assuages our own anxiety and discomfort, while the patients—our pets—continue to suffer.

The phenomenon could help explain the rising popularity of alternative veterinary therapies, from acupuncture to CBD, but it might also be skewing assessments of more conventional treatments. The regulation of veterinary medicines is “fairly loose,” McKenzie says, and the market for them relatively small. So pharmaceutical companies have little financial incentive to conduct placebo-controlled trials, which are time-consuming and expensive, when animals are the intended patients. As a result, relatively few veterinary studies have historically included a placebo group, which means that many of the mainstream treatments on offer today may be less effective than pet owners have been led to believe. (In general, veterinary trials also tend to be smaller and of lower quality than human ones, researchers have found.)

Norms and practices are finally beginning to change, and more veterinarians are coming to embrace the precepts of evidence-based medicine. Even so, McKenzie would like vets to be more transparent about how much scientific evidence exists (or doesn’t) to support the remedies they’re recommending, and to warn their clients about how human assumptions can sometimes lead us astray.

That’s not always an easy conversation. “We’re going to get resistance from people because it makes them feel like their personal experiences aren’t validated,” he says. “I always feel like it’s worth saying, when I’m talking to people about placebo effects, ‘I’m not here to say that you’re lying, that you’re stupid, that you’re just not paying attention to your pet … I make the same exact mistakes, and I do this for a living.’”

The caregiver placebo effect may be inconvenient, but it’s also a normal and natural consequence of human psychology. And in some ways, it’s a testament to how much people care about their pets—and to how desperately we want to believe that the things we do for them actually make their lives better. “The more strongly motivated you are to see something,” McKenzie says, “the more likely you are to see it.”