Collection of colorful pills (Adobe Stock Photo)
Photo credit:: Adobe Stock Photo

My mother, who lived in Israel, used to go to her doctor about once a month with a list of medication she insisted he should prescribe her. I once had a chance to look at the list, and it contained painkillers (she had no complaints of pain), antibiotics (she suffered from no infection), a blood pressure medication (she was already on beta blockers, diuretics, and ACE inhibitors), some mega doses of vitamins, and an ointment of mysterious benefits. I was aghast. “How did you get this list?,” I asked. “This one is from the neighbor on the third floor, and this one I got from a lady who goes dancing with me every week.” I felt sorry for her doctor. Alas, she and her doctor, are not alone. I had many encounters with patients, mainly from Eastern Europe, who came with a veritable shopping list of medications that they insisted I had to prescribe, or else…

I wondered how do the Israeli doctors deal with it? The answer: They prescribe a placebo!

A study by two Israeli physicians polled 31 physicians working in hospital inpatient and outpatient departments, 31 head nurses working in hospital inpatient departments, and 27 family physicians working in community clinics. And what they found was that among the 89 respondents, 53 (60%) used placebos. Among users, 33 (62%) prescribed a placebo as often as once a month or more; 36 (68%) told patients they were receiving actual medication; 15 (28%) considered that placebos were a diagnostic tool; and 48/51 (94%) reported that they found placebos generally or occasionally effective.

 

What are placebos good for?

Over the past five decades, placebos—sham treatments that mimic the therapeutic effects of real drugs or interventions—have become indispensable control measures in judging the efficacy of new therapies. Based on studies conducted in the 1950s, researchers estimate that one in three people responds to placebos. The effect may be much higher for conditions with a strong psychological component such as pain and depression. To wit, a recent article in the New York Times revealed that studies on antidepressants, which were not published by the drug companies, showed placebo effects ranging up to 60%, rendering the effect of the drug statistically non-significant. Any guesses as to why these studied remained unpublished?

The concept of a placebo as a control in clinical trials sounds pretty straightforward, except that it isn’t. When patients participating in clinical trials were asked whether they knew if they are on a placebo, most of them said they did. How? Simple—by the lack of side effects. It is almost impossible (and probably unethical) to devise a placebo that would mimic the side effects of a drug, without its benefits.

 

Is the “placebo effect” real?

Can patients really feel less pain, or reduce their blood pressure, or wipe out an infection? As you may have already guessed, it depends on the context. Patients may feel less pain on a placebo, but they could not eradicate a pathogen after receiving a placebo. In other words, it’s all in your head.

 

The neurobiology of the placebo effect

We, in the medical profession, frown on the prescription of placebos. Want proof? Just mention “homeopathy” to any physician, and brace yourself for an onslaught of derision. The fact of the matter, though, is that the placebo effect has a real neurobiological basis, and, in certain circumstances, is truly beneficial. For instance, using functional magnetic resonance imaging, University of Michigan researchers have localized placebo response to pain medicine to a distinct area of the brain. Patients whose brain scans show the strongest response also reported the greatest pain relief (Science 303, 1162−1167; 2004). Another team at the University of Turin in Italy demonstrated the effect of placebos on a single neuron in patients with Parkinson disease. The researchers showed that saline injections mimic the therapeutic effects of drugs such as L-Dopa (Nat. Neurosci. 7, 587−588; 2004). The tracing on the right demonstrates a recording of a single neuron before and after injection of saline. As they say, a picture is worth a thousand words (sounds like a Chinese pearl of wisdom you find in fortune cookies).

 

Should placebos be prescribed?

I used to think that the answer to this question is a no-brainer: Of course not, it is useless, and unethical to boot. But what if it is efficacious in controlling pain? Is it better to prescribe a powerful analgesic, with all its side effects?

If you think that the effect is limited to pain perception, here is some food for thought.

In a neat little experiment, cleaning maids in a New York City hotel were told that their work constituted enough physical activity to make them fit and reduce their blood pressure. Maids at a hotel across the street, who served as a control group, were only advised to start an exercise program. At the end of six weeks, the experimental group reported feeling in great shape and had a statistically significant, albeit small, reduction in systolic blood pressure. The control group reported no difference in well-being and showed no change in blood pressure.

And what about reports showing that blood pressure and heart rate can be reduced through meditation? Or even more surprising, it improves the immune response through elevation of the T lymphocyte count.

So, we are increasingly coming to the conclusion that the much maligned placebo effect is indeed “all in your head”—but in a much more profound sense than had been suspected.

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.