Imagine the following: You’ve been struggling to manage a patient’s irritable bowel syndrome (IBS). Standard medications have failed or produced only adverse effects. One night, after tossing and turning over this patient’s case, it hits you: Maybe a placebo would help. But, you wonder, how do I prescribe a placebo without deceiving the patient and without compromising its efficacy?

MDLinx spoke to two leading placebo researchers on the subject. One said that placebos can be prescribed ethically and effectively to patients with functional diseases with likely central sensitization, and the other described how effective communication alone may trigger the placebo effect.

 

Assessing placebo usage

A 2018 meta-analysis published in PLoS One indicates that general practitioners (GPs) and family physicians may be liberally using pure placebos, such as sugar pills, as well as non-specific therapies, such as prescribing antibiotics for a cold.

Linde K, Atmann O, Meissner K, et al. How often do general practitioners use placebos and non-specific interventions? Systematic review and meta-analysis of surveys. PLoS ONE. 2018;13(8):e0202211.

 

After identifying 16 studies from 13 countries for inclusion, researchers found that throughout a GP’s career, as many as 97% had prescribed a placebo at least once in their career.

GPs used non-specific therapies far more often than pure placebo: Up to 89% for monthly prescription of non-specific therapies, compared with up to 15% for pure placebos.

If done correctly, there’s nothing wrong with this. The AMA offers a framework for prescribing placebos in its Code of Medical Ethics.

Use of placebo in clinical practice. American Medical Association.

 

“In the clinical setting, the use of a placebo without the patient’s knowledge may undermine trust, compromise the patient-physician relationship, and result in medical harm to the patient,” the AMA wrote.

To prescribe a placebo ethically, the AMA advises that physicians:

• Explain that exploring all medications, including placebo, could lead to a more comprehensive understanding of the condition.

• Get informed consent before prescribing. However, the patient does not need to know when the placebo is used.

• Avoid using placebos to placate patients. Doctors can achieve a placebo effect simply by encouraging and reassuring patients.

However, the research on placebo transparency may surprise you.

 

Open-label placebo

Ted Jack Kaptchuk is a professor of medicine, and of global health and social medicine, at Harvard Medical School. He’s also director of its Program in Placebo Studies and the Therapeutic Encounter. According to Kaptchuk, open-label placebo (OLP) studies have shown that some patients benefit from the placebo effect, even when they're told upfront about the placebo and give full informed consent.

“When we started this research trajectory, we would say that OLP had never been tried and we wanted to see what would happen if you took a placebo and knew it,” Kaptchuk said.

We never lied about what to expect, never lied about what is in it, or exaggerated expectations.

In a 2021 research paper published in Pain, Kaptchuk and a team of researchers compared the efficacy of OLP with no-pill control (NPC) and double-blind placebo (DBP) in IBS management.

Lembo A, Kelley JM, Nee J, et al. Open-label placebo vs double-blind placebo for irritable bowel syndrome: a randomized clinical trial. Pain. 2021;162(9):2428-2435.

Over 6 weeks, 262 adults received OLP, DBP, or NPC interventions. Compared with NPC, participants who received OLP saw greater, statistically significant improvements in their IBS Severity Scores (90.6 vs 52.3, P=0.038). For OLP compared with DBP, IBS Severity Scores were similar (100.3 vs 90.6, P=0.485).

 

“This study confirms our previous finding in IBS that OLP is superior to usual care (ie, NPC) and challenges the widely held assumption that blinding is necessary for participants to improve with placebo,” the researcher wrote. “The results of this study suggest, however, that deception may not be necessary, and that, at least in some conditions, patients may still show improvement even when prescribed OLPs.”

According to Kaptchuk, honesty and transparency are integral to the success of OLP.

“We are meticulous in being honest,” Kaptchuk said. “In fact, patients can smell lies and, given the taint of deception that placebos have, any dishonesty would destroy the effect of OLP.”

 

The placebo effect and empathy

Felicity Bishop, MSc, PhD, a placebo researcher based at the University of Southampton, said that when used properly, placebos should fall within the normal scope of patient-provider conversations.

“Having open discussions with patients about treatment options is vital for fostering trusting therapeutic relationships, involving patients in treatment decision-making, and respecting their right to autonomy,” she said.

In fact, Bishop’s latest research explores how physicians can harness the placebo effect that almost all medical treatments will have, without prescribing a placebo—all while respecting patient autonomy.

In a 2021 article published in Frontiers in Pain Research, Bishop and a team of researchers outlined how a clinical communication training protocol, which leverages the latest findings in placebo-effect research, can tap into the placebo effect for osteoarthritis patients.

Smith KA, Vennik J, Morrison L, et al. Harnessing placebo effects in primary care: Using the person-based approach to develop an online intervention to enhance practitioners’ communication of clinical empathy and realistic optimism during consultations. Front Pain Res (Lausanne). 2021;2:721222.

 

The protocol, called Empathico, is an evidence-based, theoretically grounded intervention that should “enable practitioners to better harness placebo effects of communication in consultations,” the researchers wrote. Specifically, the protocol trains clinicians to harness the placebo effect inherent in empathy and realistic optimism for osteoarthritis patients.

“By communicating realistically positive messages with clinical empathy, doctors may be able to enhance the effects of evidence-based treatments—strengthening placebo effects without prescribing placebos,” Bishop said.

 

Putting placebos into practice

Regardless of whether you harness the placebo effect through communication or more traditional means, the implications are the same: ethics and transparency are paramount. Kaptchuk offered the following guidance:

• If applicable, voice your skepticism: If you’re skeptical about whether the placebo will work, the honest thing to do is tell the patient.

• Cite the evidence: “We know that neurotransmitters are involved with placebo response and that specific, quantifiable, and relevant regions of the brain are engaged,” Kaptchuk said as an example.

• Explain that results will vary: Some patients will see a benefit quickly, others gradually.

• Be open to possibility: “Say something like ‘Let’s see what happens.’ Uncertainty is part of why OLP treatment can modify central sensitization to provide relief.”

Above all else, Kaptchuk said “honesty is key.”

Using any kind of deception and positive-expectation manipulation is unethical.