The “honest” placebo: When drugs still work even though patients know they're fake

A new study has found patients suffering from cancer-related fatigue displayed significant improvement in their symptoms after being given an inert placebo. All the subjects were told at the beginning of the study that the pills they were being given contained no active pharmacological ingredients, yet a notable placebo effect was still identified. This new study adds to a compelling growing body of work suggesting "honest" placebos could play a role in certain kinds of clinical treatments.

Back in 2010, Ted Kaptchuk, a Harvard Professor of Medicine, published the results of a small trial that challenged an assumption that had held strong in science for decades. Kaptchuk wondered if deception was really necessary for the placebo effect to take hold. Could a beneficial placebo effect be identified even when a patient was knowingly taking a sugar pill?

A cohort of 80 patients suffering from irritable bowel syndrome (IBS) was gathered. Half were designated as a control group, receiving no treatment, while the other half were given placebo pills and instructed to take them twice a day for three weeks.

"Not only did we make it absolutely clear that these pills had no active ingredient and were made from inert substances, but we actually had 'placebo' printed on the bottle," says Kaptchuk. "We told the patients that they didn't have to even believe in the placebo effect. Just take the pills."

The results surprised everyone involved, with 59 percent of the placebo cohort reporting that the fake pills did indeed result in clinically meaningful symptom improvements, whereas the control group reported only a 35 percent improvement in symptoms. The study raised a whole host of unexpected questions, but most of all it challenged the general assumption of the primary mechanism behind the placebo effect – belief.

Lies that heal

Harvard science historian Anne Harrington once described placebos as "lies that heal," and the history of medicine is littered with inexplicable stories of patients suddenly recovering from severe conditions after being administered a random remedy. But after Kaptchuk's revealing open-label placebo study was published, scientists began to investigate whether the power of placebos could actually be viably incorporated into some clinical treatments.

Over the last seven or eight years there have been a number of different trials investigating the effects of open-label placebos across a variety of conditions. Advocates of "honest" placebos are realistic about the broad variations one generally finds in the placebo effect across different conditions. In some trials the placebo effect can be non-existent, while in other instances it can be alarmingly significant.

A major review of the placebo effect across a number of clinical conditions in 2010 did conclude that, in general, placebos produced no important beneficial effects. However, homing in on more specific outcomes, the reasonably critical review did admit to finding evidence of beneficial effects in some situations that relied on patient-reported outcomes, such as pain and nausea.

So far, the growing body of study into open-label placebos has revealed positive effects in patients with back pain, nausea, IBS and migraine. Of course, centuries of bizarre medical solutions have proven that a small volume of patients can seemingly recover from almost any condition regardless of whatever crackpot solution is administered.

So how can modern medicine ethically harness the power of placebos?

Every good doctor should have a couple of white or blue sugar pills handy

A startling report commissioned by the German Medical Association, and published in 2011, revealed that more than half of all doctors in the country have at some point prescribed a patient a placebo. Robert Jütte, lead author of the report, followed up the publication saying, "The placebo effect plays a critical role in every day practice. Every good doctor should have a couple of white or blue sugar pills handy."

Unsurprisingly, the report and Jütte's subsequent comments, proved controversial, with many claiming the call for doctors to use more placebos simply, "violates the principles of medical ethics." But more research has revealed doctors apparently prescribe different kinds of placebos more often than many had ever realized.

A 2013 study of over 700 GPs in the UK revealed that almost every single doctor surveyed had prescribed a placebo at some point in their career. More specifically, 10 percent had prescribed "pure" placebos, meaning a literal sugar pill or some other inactive compound, while 98 percent had at some point administered a treatment containing an "impure" placebo, meaning a drug with active ingredients that lacked value for the condition being treated. These "impure" placebos ranged from probiotics for diarrhea, to antibiotics for viral infections.

It is difficult to argue with critics citing ethical problems over a doctor prescribing a patient a placebo with the pretense of it being a real, and beneficial, drug. However, this is where Kaptchuk's "honest" placebo research comes strikingly into focus. If deceiving a patient is not necessary to garner the beneficial effects of a placebo, then the path to incorporating them into mainstream medicine suddenly becomes much clearer.

"Fooling or deceiving patients may be unnecessary for placebo effects to produce benefits, with automatic neurological processes being a possible mechanism for the effects," explains Teri Hoenemeyer, a scientists working in open-label placebo research. "This has revolutionary implications for how we might exploit the power of placebo effects in clinical practice."

This is all still pretty fringe stuff – and even Kaptchuk is the first to admit he has no idea how placebos still work when a patient is aware they are taking a fake drug. This is undoubtedly an odd corner in the medical research world, and more work will need to be done to establish a real-world practical outcome, but Kaptchuk is convinced the work will ultimately lead to something positive.

"It doesn't work in everyone – that's clear," Kaptchuk says, in an interview with Vox. "And we don't know what makes it work, exactly. But we do know with double-blind studies with placebo – deceptive studies with placebo – that [neuro]chemicals are activated, regions of the brain are engaged that are specific and relevant – there's something going on. And I don't think it's belief."

The new study was published in the journal Supportive Care in Cancer.

Source: Dana-Farber Cancer Institute