Placebos Sometimes Work

A placebo is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets like sugar pills, inert injections like saline, sham surgery, and other procedures. In general, placebos can affect how patients perceive their condition and encourage the body's chemical processes for relieving pain and a few other symptoms, but have no impact on the disease itself.

Sick people were occasionally cured by nothing more than a 'shock to the mind'

No one knows exactly when, or how, or why placebo effects came into existence, but chances are these hidden skills have been with humanity for quite some time. The ancient Greek physician and philosopher Galen must have been observing some versions of the phenomena when he marveled that sick people at the temple of the healing god Aselepius were occasionally cured by nothing more than a 'shock to the mind.' Much later, in 1807, Thomas Jefferson wrote favorably of the perpetration of 'pious fraud' by doctors: “One of the most successful physicians I have ever known has assured me that he used more bread pills, drops of colored water, and powders of hickory ashes, than of all other medicines put together.” ¹ Fabrizio Benedetti, an Italian neuroscientist considered one of the world's preeminent placebo researchers has this to say: “I think that placebos are more about care than cure. You feel better about yourself, your condition. You have better quality of life, your symptoms aren't as bad, at least temporarily.” He adds, “Placebos don't work everywhere. They are really effective in pain, anxiety, depression, and motor disorders like Parkinson's. But, at least as far as we know today, they don't work at all in conditions such as cancer and infectious diseases.” ¹ Over the last several years, evidence has been accumulating that placebo effects are becoming more powerful. Clinical trials on a range of medications used for treating both psychological and medical problems are finding that differences in the magnitude of their impact relative to placebos are decreasing in size. ² Researchers looked at randomized controlled trials of medications for neuropathic pain for roughly 20 years. They considered 80 studies involving 92 drugs. A 16% advantage of active medication over placebo was reduced to 9% over those years. The cause: “We find that placebo responses have increased considerably over this period but drug responses have remained stable, leading to diminished treatment advantage.” ³ Age and gender did not seem to play a role; non-caucasian participants seemed to be more responsive to placebos. But the real problem appeared to be the design of the studies. Specifically, longer studies favored placebos, but they also did not demonstrate increasing study populations or study length, suggesting that indeed these are pertinent factors in designing efficacy trials.

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The placebo effect has become stronger in the United States, but not in Europe

Many factors frame the placebo response in addition to the ones elicited in this study. Prescribing a placebo involves the physician, patient, and placebo itself. Studies have shown that the mode of placebo delivery can enhance its effect—injections are taken 'more seriously' than rubbing on some lotion. ⁴ Interestingly, in the case of pain medications, the placebo effect has become stronger in the United States, but not in Europe. What might account for this difference? One possible factor is that the United states allows direct advertising to consumers, while European countries do not. Thus, American consumers are more primed to expect positive benefits from pain medications than Europeans. This explanation is particularly plausible given the fact that pain perception is strongly mediated by psychological factors. ² A Program for Placebo Studies at Harvard Medical Schools (PiPS) consists of an interdisciplinary team that explores the impact of the patient-physician relationship, hope, trust, persuasion, and other psychological and interpersonal variables on the healing process in medicine. This program has received widespread media attention and is playing an important role in stimulating a broader interest in the area of placebo studies. It's the first program in the world devoted to the interdisciplinary study of the placebo effect. ² One of the key elements of the placebo effect is the way our expectations shape our experience. Functional MRI and other new technologies are showing that placebos, like other new pharmaceuticals, actually trigger neurochemicals such as endorpins and dopamine, and activate areas of the rain associated with analgesia and other forms of symptomatic relief. What might the future of placebo look like? Ted Kaptchuk, founder and director of PiPS, talks about doctors one day prescribing open-label placebos to their patients as a way of treating certain symptoms, without all the costs and side effects that can come with real pharmaceuticals. Other researchers, including those at the National Institute of Mental Health, are focusing on placebo's ability to help patients with hard to treat symptoms, such as nausea and chronic pain. Still others talked about using the symbols and rituals of health care to maximize the placebo component of conventional medical treatments. ⁵

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Another Approach

Placebo groups have long been viewed as a necessary evil by the medical profession when no other option is available. For over a century, placebo trials have been the best way to test new and experimental drugs. But now clever math and real-world data are letting us do away with placebos altogether. A potential solution to the ethical quandary raised by placebo groups is on the horizon. The digitization of health records means real world evidence such as doctors' notes and pathology reports could be used to create a synthetic control arm to replace clinical trials' existing control arms. This means rather than having patients taking a placebo in a clinical trial, the same results can be achieved by identifying patients in the real world at the same stage of illness and with in a similar demographic. The same methodology that would usually be applied to analyze a control group can be applied to real world data to generate results that can be compared against the new treatment. ⁶

References

1. Melanie Warner, The Magic Feather, (New York, Scribner, 2019)
2. Jeremy D. Safran, “The curious case of the growing placebo effect,” psychologytoday.com, March 20, 2018
3. Alexander H. Tuttle et al., “Increasing placebo responses over time in US clinical trials or neuropathic pain,” Pain DOI: 10.1097/j.pain
4. Chuck Dinerstein, “Every picture tells a story: placebo effect,” acsh.org, December 8, 2021
5. Robert Anthony Siegel, “Why I take fake pills,” Smithsonian Magazine, May 2017
6. Matthew Chapman, “The end of placebos is in sight,” Wired, December 3, 2019