Personalized placebo effect

A new article in Nature explores the placebo effect–therapeutic benefit from taking medicine without active ingredients. On the one hand, minimizing the placebo effect is a principle of ethical medical practice, a bulwark against hype, oversell, and charlatanism. Without controlling for therapeutic effects not caused by the drug, one may overestimate the drug’s potency. On the other hand, if the goal is to make the patient well, one might consider it ethical to use every option available—including whatever mysterious mechanisms the body can muster to augment the pharmaceutical therapy. The oldest tradition in medicine is that of helping the body heal itself.

Most interestingly, the placebo effect is highly individualized. This is not surprising, given the complex psycho-somatic interactions involved. Yet in an age in which personalized medicine is the idea of the moment, it seems essential to open the black box of the placebo effect. The authors summarize not only psychosocial variables known to influence patients’ responses to drugs—expectations, anxiety states, hypnosis, and so forth—but also a range of genetic and anatomical correlates of placebo responses. The strongest data are in the area of drugs for anxiety disorders and depression. Documented examples include polymorphisms in serotonin loci and in modulators of monoaminergic tone, plasma noradrenaline levels in interleukin-2 release, and brain anatomy in placebo analgesia.

Such data are exciting in historical as well as therapeutic context. In 1902, at the dawn of Mendelism, Archibald Garrod suggested that humans were as variable and individualized at the biochemical level as they are at the phenotypic level. If this were true, he continued, the phenomena of obesity, the various tints of hair, skin, and eyes, and “idiosyncrasies as regards drugs and the various degrees of natural immunity against infections” could be amenable to biochemical-genetic analysis.

Rufus of Ephesus
Rufus of Ephesus

Going further back, the Hippocratic physician Rufus of Ephesus noted that drugs act differently on different people, and that to prescribe appropriately the physician must ask the patients about their habits, their diet, preferences, sleep patterns, familial diseases, degrees of pain, and numerous other facets of the patient’s history and context. For the Hippocratic physician the body’s own powers of healing, mysterious though they be, were a crucial component of therapeutics. The Nature article’s abstract concludes with a nice statement of individuality that sounds like updated Hippocratism:

Personalizing placebo responses — which involves considering an individual’s genetic predisposition, personality, past medical history and treatment experience — could also maximize therapeutic outcomes.

Personalized medicine is often portrayed as a return to ancient Hippocratic ideals. It is and it isn’t. Despite the hype, “one-size-fits-all” medicine is too cost-effective to abandon. Personalized medicine has always been reserved for those who can pay for it, and little in the age of high-tech genomic medicine seems likely to change that. And yet, this attention to the unique constellation of essential and historical factors that combine in a given patient’s “irrational” drug response does bode well to be anodyne against some of the dehumanizing forces in the recent history of medicine.


14 thoughts on “Personalized placebo effect”

  1. So do you suppose, from a genetic standpoint, that patients who experience significant placebo effects have an excess of pseudogenes?

  2. Although some pseudogenes can produce what are thought to be functional RNA or protein, it’s most likely due (in part) to individual differences in epigenetics and alternative transcription and translation of known functional genes.

  3. So where does such an explanation leave the neo-Hippocratic attention to life history, experience, and context? Do genetics and epigenetics simply provide a mechanistic explanation of those broad contextual variables, or is there truly a place for historical understanding of the patient in modern genomic medicine?

  4. Great question! Here’s my great answer 😉

    Within the narrow framework of the placebo effect, it seems to be the personal interaction with a health care provider that truly makes the difference. As they say in the article, “there is a ‘dose-dependent response’ for a placebo: the more care people got—even if it was fake—the better they tended to fare.”

    But of course not all treatments perform at the same level (or worse) than placebo. The hope I would imagine is that paying attention to life history, experience and context will allow for a better treatment selection when more than one option is available.

  5. Fascinating. Thanks for the link. This is a great example of the value of individualized care. I’ll pass this along to the students in my course on individuality in medicine.

    • Hey, I! We tend to be up, too! And complete sentences! Keep up the amazing English guys and add more pictures and other nationalities and genders as well.

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