TSMP: If Placebos Work So Well, Why Not Prescribe Sugar Pills For Everything?

A Sunday Morning Post about the strange wonder of placebo effects in medicine and society, with brief appearances by Indiana Jones and William James

Photo by Sebastien Gabriel on Unsplash

Welcome back to The Sunday Morning Post. The goal of TSMP is that every post violates the rules of the news cycle by sharing news on science, health, and history that will be as relevant in 10 years as in 10 hours. Today, a brilliant essay on placebo effects gets me thinking about the power of expectation in medicine and beyond.

---

In 1995, a 29-year-old construction worker arrived at Leicester Royal Infirmary with a six-inch nail through his boot. He was shouting in pain. Every attempt to extract the nail made the screams louder. Finally, a team sedated him and removed the boot. They looked at the nail. No blood. They looked at the foot. No wound. The nail had pierced nothing but the empty space between his toes. The physical injury wasn’t real. Only the pain was.

Our beliefs about our bodies shape our experience of our bodies, just as beliefs about our lives shape our lives. The spooky nature of placebo effects—or beneficial outcomes from inert treatments—is the subject of several new books including Placebos by Kathryn T. Hall and The Power of Placebos by Jeremy Howick, which are the source material for a spectacular recent essay by the physician and author Gavin Francis.

As Francis explains, placebos work best when “subjective interpretation of symptoms” plays a large part in the illness. If you have late-stage lung cancer, sugar pills will do nothing for you. But if you’re suffering from an illness with a psychological layer—pain, insomnia, depression, or anxiety—expectation is its own medicine. As the science podcaster Shankar Vedantam wrote in The Washington Post several decades ago:

After thousands of studies, hundreds of millions of prescriptions and tens of billions of dollars in sales, two things are certain about pills that treat depression: Antidepressants like Prozac, Paxil and Zoloft work. And so do sugar pills.

One might suspect that placebo effects are a function of the human brain’s extraordinary capacity for imagination. But animals with less cognitive juice have the same abilities. In one study, scientists gave rats a strong immunosuppressant drug along with a bit of artificial sweetener. Later, the rats got the sweetener without the drug. Their immune systems crashed anyway. It was as if their bodies anticipated a series of chemical reactions from a medicine that was never administered.

Placebo derives from the Latin word meaning “to please,” and the effect refers to positive side effects. Its cousin is the nocebo effect, which is a negative outcome from an inert treatment or stimulus. Some years ago, Francis tells us, a man participating in a clinical trial for a new antidepressant drug took too many pills. When he arrived at the hospital to check in for a likely overdose, his blood pressure crashed. Rushed to the emergency room, he discovered, alongside the doctors, that he had not suffered any medical side effect. He had been taking sugar pills. His blood pressure plummeted, not because of any medication, but rather because of his solemn faith in the power of a medicine he wasn’t taking.

Perhaps the strangest examples of placebo and nocebo effects in both directions come from sexual dysfunction studies, which are so exquisitely sensitive to expectations that all sorts of drugs can be used to either treat or cause erectile dysfunction. Francis reports:

Ninety-six men [participated] in a study of a beta-blocker called atenolol, which has the potential to cause impotence. Of the men given no information about this side effect, only 3.1 percent developed impotence, and among those given only the name of the drug, 15.6 percent developed it. But of those who were told both the name of the drug and that it might cause impotence, 31.2 percent developed erectile dysfunction.

All of those complaining of impotence were then randomized to receive either a placebo or sildenafil (Viagra) to treat the problem; the former was just as successful at restoring erections as the latter. Similarly, of men given finasteride for prostate problems, 43 percent who were told it might cause impotence experienced the problem, against 15 percent who were not warned of side effects.

As John Milton’s devil quite nearly said, the mind is its own place, and in itself can make Viagra out of a sugar pill, and a sugar pill out of Viagra.

So, Sugar Pills For Everything, Yes?

If you’re like me, and you spend a lot of time thinking about how hard and expensive it is to invent great new medicines, you might be thinking: Wait, should we be giving people placebos for everything?

According to Kathryn T. Hall, the German Medical Association allows placebos to be prescribed “for patients with a minor condition, when there is no other effective treatment available, and when treatment with a placebo is likely to succeed.” If, for example, drugs have failed a patient experiencing chronic pain, doctors can prescribe placebos. In the U.S., the American Medical Association says that physicians can only prescribe placebos with the patient’s general consent. This might initially seem almost comically self-defeating (“ma’am, very sorry about the headache, but would you like a pill from this jar labeled EXTREMELY FAKE MEDICINE?”). More subtly, doctors can fudge the language by asking patients if they consent to something like “try different medicines, including placebos” to retain the power of self-fulfilling improvement.

Francis thinks that modern medicine doesn’t take enough advantage of placebo effects in the treatment of diseases with a psychological or psychosomatic layer. “A revolution is long overdue,” he writes, “as the costs of conventional medicines spiral ever upward and the returns on those costs diminish.” Doctors ought to experiment with “more use of honest placebos,” he says, “because they work.” European doctors have historically been more willing than their American counterparts to prescribe sugar pills and harmless vitamins for chronic pain, anxiety, or fatigue. I have a hard time imagining that a country with America’s fiercely consumerist ethic would accept such a norm, even if doctors made the case that placebos have fewer side effects than SSRIs and painkillers. Americans don’t want to feel “tricked”—even when, in the case of placebos and nocebos, it is our own minds that are doing the tricking.

In fact, the medical industry is already constantly administering placebos, even when it isn’t trying to. The rituals of modern health care—the white coats, the stethoscopes, the antiseptic hallways—convey to many patients an expectation of competence and expertise that can lead to actual improvement. In clinical therapy, it is hard to know where treatment effects begin and placebo effects end. Successfully treating anxiety, PTSD, or phobias is practically impossible without the emotional consent of the patient, the psychological expectation that therapy might work, or even false attributions on the part of the patient¹—all of which might, in a pharmacology context, be called a placebo. When I tell my friend that he should see a certain counselor to work on his anxiety “because it worked well for me,” I’m passing along an expectation of success that can cause more success.

Patients do not live in the world as it “is” so much as they occupy the world as they expect it to be. Their expectations make their environment, and this principle extends far beyond pain and medicine.

Where on This Moonlit and Dream-Visited Planet

In 1896, William James published a lecture entitled “The Will to Believe,” which offered a defense of faith in the absence of evidence. James was responding to contemporary intellectuals who criticized religion by insisting that it was always wrong to believe something without proof. Like much of James’ work, the essay is so light on its feet and insightful on a paragraph-to-paragraph basis that any attempt to fully summarize it will inevitably flatten many of its deepest joys. But perhaps the most important point for our purposes is his contention that belief without evidence is not only an inevitable feature of life but also a virtue of a life well lived.

“Objective evidence and certitude are doubtless very fine ideals to play with, but where on this moonlit and dream-visited planet are they found?” James writes. Belief and reality, he said, cannot be fully separated, because our beliefs are constantly building our reality; “faith in a fact can help create the fact.” In medicine, faith in the fact of recovery creates the fact of recovery, and this is what we call placebo. In life, James says, faith without evidence allows us to do what we otherwise wouldn’t, and this is what we might call courage.

Suppose, he says, that you are stuck on a mountain pass and have the bad luck to find yourself trapped in a position where the only escape requires jumping across a crevasse. It is hope, confidence, and nerve that allow you to make the leap. If, on the contrary, you are overcome with fear and mistrust in your balance, you may die of freezing or otherwise slip into the abyss. When we need courage, “faith creates its own verification,” James writes. “Believe, and you shall be right, for you shall save yourself; doubt, and you shall again be right, for you shall perish.”

The self-fulfilling power of belief is not limited to individual medicine or to hypothetical mountain hops. Belief is most powerful at the level of groups. “A social organism of any sort whatever, large or small, is what it is because each member proceeds to his own duty with a trust that the other members will simultaneously do theirs,” James writes. The competence of an army or a sports team depends exquisitely on the beliefs of its individual members in the fiction of the collective enterprise. A cavalry cannot function if each member requires constant irrefutable evidence that the men around him won’t ride away. An NFL offense would never get a play off if each player demanded absolute confidence that everybody else would only execute their positions perfectly. To do your job with the conviction that people around you will will do theirs is not what anybody would call a religion, and yet it depends on what Kierkegaard would have recognized as a leap of faith.

In the absence of trust, what James calls a “social organism” breaks down. At the societal level, many people’s belief in their own social anxiety has created the conditions for collective social isolation. “People are way too negative about their own social abilities,” the psychologist Adam Mastroianni said. One reason why many people avoid conversations with people they don’t know well is that “they underestimate how pleasant it’s going to be to talk to someone new,” even though science has shown that people enjoy deep conversations with strangers much more than they expect. Aloneness and loneliness, in this interpretation, are the result of a kind of society-wide nocebo effect. The commonplace belief that we might bore others, or that people might threaten our self-esteem, reduces social interaction in a way that literally makes us more boring and less happy. Or, as James might have put it, “faith in the fact of our social ineptitude creates the fact of our social isolation.”

Rather than see placebo as a narrow feature of medicine, one might see it as a common feature of life. Faith is constantly creating its own verification. Like Indiana Jones at the temple of the Holy Grail, we leap, and it is the leap that builds the bridge. William James ends his lecture this way—and we’ll do the same:

In all important transactions of life we have to take a leap in the dark … We stand on a mountain pass in the midst of whirling snow and blinding mist, through which we get glimpses now and then of paths which may be deceptive. If we stand still we shall be frozen to death. If we take the wrong road we shall be dashed to pieces. We do not certainly know whether there is any right one. What must we do? ‘Be strong and of a good courage.’ Act for the best, hope for the best, and take what comes. If death ends all, we cannot meet death better.”

1. Consider, for example, a hypothetical woman whose clinical depression lifts after 10 sessions with a psychologist because, between the 5th and 10th sessions, she discontinued a birth control pill that was having a negative neurotransmitter effect. After mistakenly attributing her improvement to the help of her psychologist, she might keep her therapist around, and the strong belief that “therapy works” might go on to lead to all sorts of positive psychological effects that have nothing to do with the quality of the treatment.