Pharma shudders as study says placebo effect real and growing.

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The News:

Cancer survivors may be able to manage the extreme fatigue they experience after treatment by knowingly taking a placebo pill, according to researchers at University of Alabama at Birmingham and Harvard Medical School.

After treatment, cancer survivors still experience extreme fatigue with few treatments available on the market to help these former patients deal with exhaustion, and the best treatments to alleviate fatigue have many side effects, including panic, psychosis, and heart failure.

A study published in Nature Scientific Reports found that cancer survivors who were advised to take placebo pills reported a 29% improvement in fatigue severity and a 39% improvement in fatigue disrupting the quality of life, according to Kaitlynn Ely at the American Journal of Managed Care.

“Cancer survivors report that fatigue is their most distressing symptom, even more distressing than other symptoms like nausea or pain, and clinicians struggle to find ways to help them with it,” Teri Hoenemeyer, PhD, lead author and director of Education and Supportive Services at the UAB Comprehensive Cancer Center in a press release. “The effects of the placebo pills on fatigue were so dramatic that we had a number of the study patients ask if they could be given more placebo pills. For ethical reasons, we were unable to do so.”

74 survivors of different types of cancer who reported feelings of fatigue were included in the study. Half were assigned a pharmacological treatment while the other half knowingly took two placebo pills, twice per day, for three weeks.

The novel use of placebo in the new study differs from the standard use of placebo in clinical trials, Hoenemeyer told Medscape.

“Researchers will use a concealed placebo so that the participant thinks they are getting the drug/intervention. In our study, we actually told the participant that they were getting a placebo,” she said.

She added that the latter is called an open-label placebo. This is the first open-label placebo study in a cancer population with a chronic adverse condition.

The American Medical Association states that medical use of placebos is ethical as long as physicians tell patients that the treatment is a placebo, said Hoenemeyer.

The power of placebo is still a mystery, she added: “Amazingly, while we may know about placebo effect, we do not understand it. As placebo researchers, we are still trying to untangle why placebos work.”

Steve’s Take:

Steve's Take: Call it, “The Emergence of the Clinical Reality of the Placebo Effect.” And if that doesn’t strike terror into the marketing and R&D corridors at Pharma, I don’t know what will. Click To Tweet

One of the findings of this ground-breaking study made me chuckle:

“Participants still had benefits three weeks after they stopped taking the placebo pills, which hasn’t been shown before,” explained Kevin Fontaine, PhD, co-author and chair of the Department of Health Behavior in the UAB School of Public Health. “The extension of benefits even when the placebo pills are discontinued has been a surprise finding that has many placebo researchers excited.”

Oh indeed, I can well imagine researchers’ excitement with these findings. I can also picture pharmaceutical executives squirming at their desks and racking their marketing brains as to how to counter findings that heretofore have remained in a closet, safely tucked away from consumers. And just what is this worrisome finding for the pharma industry?

Call it, “The Emergence of the Clinical Reality of the Placebo Effect.” And if that doesn’t strike terror into the marketing and R&D corridors at Pharma, I don’t know what will. After all, placebo effect’s price tag is $0. Compare that with the cost of a competing pharmaceutical.

The fact is that over the last several years evidence has been accumulating that placebo effects are becoming more powerful, according to Psychology Today (PT). 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.

For example, in the early 2002, Merck (the US one) was on the verge of releasing a promising new antidepressant (codenamed MK-869). The development and preliminary testing of MK-869 had been exorbitantly expensive, but it was about to pay off.

MK-869 had performed brilliantly in early clinical trials–better than several other popular antidepressants on the market. In what has become an increasingly common story, plans for releasing MK-869 ultimately came to a halt after evidence accumulated that the new medication failed to outperform placebo treatment.

For pharmaceutical companies, the growing power of antidepressant placebos is a vexing problem, resulting in a substantially reduced investment in this area, says PT.

The growing potency of placebos is not limited to psychiatric drugs. When researchers started looking closely at pain-drug clinical trials, they found that an average of 27% of patients in 1996 reported pain reduction from new pain medications being developed relative to placebo pills.

By 2013 that difference had shrunk to just 9%. In the last decade, more than 90% of painkillers developed in the US have failed to show a significant improvement over placebos in the final stages of clinical trials.

At this point we can only speculate about the factors contributing to the growing potency of placebos, PT asserts. While research into the mechanisms underlying the effects of placebo treatments is in its infancy, we do know that increasing people’s expectations regarding the occurrence of a non-volitional response increases its likelihood of occurring.

This type of expectancy effect plays a key role in hypnotic suggestion. For example, in hypnotizable subjects a hand levitation induction can lead subjects to experience their hands as spontaneously rising. Expectancy effects of this type can activate psychological and autonomic nervous system changes as well.

One possibility is that public expectations regarding the potency of specific types of medications are increasing, PT notes. In the case of psychiatric drugs there has been a growing shift towards viewing emotional problems from a disease model perspective and to consider medication–rather than psychotherapy–as the treatment of choice.

For example, since the late seventies when Prozac and other selective serotonin reuptake inhibitors first came out, and the widespread publicity associated with this new generation of drugs, antidepressant use in the US has soared by over 65%. In fact, antidepressants are now the third most commonly prescribed medication in the country.

Interestingly, in the case of pain medications, the placebo effect has become stronger in the US, but not in Europe. What might account for this difference?

One possible factor, is that the US allows direct advertising to consumers, while European countries do not. Thus, Americans 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.

Bottom Line:

While the growing power of placebos is a major problem for pharmaceutical companies, it does bring home the importance of conducting research on the mechanisms underlying the impact of the placebo effect. And then there’s the Nocebo: the placebo effect’s evil twin. This is where negative expectations about treatment lead to side effects that can have a huge impact on clinical outcomes.

“Belief is key,” says Sharon Roman in BMJ, Feb. 27, 2018. “But not just for patients. Doctors need to believe that they themselves can sometimes be a placebo and influence a patient’s life.”

Surprisingly, it is possible to begin building that power in the waiting room, Roman notes.

“Those usually dark and dated rooms, which so quickly extinguish any levity or humor, can give rise to anger, fear, and despair. (Any laughter there is usually met with a glance from others as if to say, ‘don’t you know we are sick?’”) When her doctors come to meet her and show her in, “their greeting and broad, sincere smile brightens any room to me. No amount of expensive decor could best that feeling.”

Mutual trust and respect, happiness, a warm smile, a touch of the arm, or a handshake coupled with sincerity–and yes, even a touch of humor–help make for an uplifting appointment when you live with a chronic disease, Roman adds:

“My relationships with my doctors and my healthcare team–it’s the best medication that I have never taken.”

Sorry Big and small pharma. The placebo effect is real and growing. Just figure out why and add it to your products. Or maybe not.

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