Tag Archives: Medicine

A ‘weapon against the placebo effect’ …?

It seems that this damned placebo effect is getting in the way of developing and authorising new psychiatric drugs. It creates a ‘therapeutic bias'(!) and so the experimenters are experimenting with ways of controlling for it in trials, for example ‘SPCD, sequential parallel comparison design’. These are proving to be not (yet) up to the task, sufficient to be acceptable by bodies such as the RDA. The following is from The Placebo Effect Is Hobbling New Psychiatric Drugs

“The FDA’s rejection cast doubt upon the design, still in use in more than a dozen trials, as a weapon against the placebo effect.

That’s big news because the effect, also called the placebo response, has been growing stronger over the years in clinical studies that randomly assign patients to either an active drug or placebo. When the effect is high, it’s hard to know if a drug just isn’t good enough, if there are errors in the data, or if the participants taking the placebo—an inert pill meant to make them believe they’re getting the real thing—fared unusually well because of their expectations.

It’s a testament to the power of our minds to improve our health, at least temporarily. Many factors boost placebo response. “Most people, whether they know it or not, are biased to believe that they will receive the active drug even if they are told that they have a 50 percent chance of getting placebo, and this ‘therapeutic bias’ increases the placebo response,” says John Krystal, the chair of the psychiatric department at the Yale School of Medicine in New Haven, CT.”

Placebo as Science

Henry K. Beecher

What is now emerging as ‘placebo science’ has its roots in an influential 1955 paper entitled ‘The Powerful Placebo’ by Henry K. Beecher which proposed that placebo effects were clinically important. This remains the most commonly-cited placebo reference.

Henry Knowles Beecher (February 4, 1904 – July 25, 1976) was a pioneering American anesthesiologist, medical ethicist, and investigator of the placebo effect at Harvard Medical School, which now, fittingly enough, co-convenes the Program in Placebo Studies & Therapeutic Encounter (PiPS)
with the Beth Israel Deaconess Medical Center.

The prestigious Beecher Prize, named in his honor, is awarded annually by Harvard Medical School to a medical student who has produced exceptional work in the field of medical ethics.

Preventing Nocebo Effects

We all know about the ‘nocebo’ effect by now – the dark twin of the beneficial placebo effect. For example, a study showed that the pharmacological efficacy of remifentanil (a pain medication) was significantly decreased after patients were told the infusion was stopped during a heat-pain modulation test. Although the infusion had not actually been halted, participants experienced a significant exacerbation of pain even while still receiving remifentanil.

To counter undesirable ‘nocebo’ effects, this article suggests to health practitioners that ‘pragmatic strategies related to patient–practitioner interaction, clinical setting, and context may be implemented to help minimize and prevent the consolidation of negative expectations’.

Expectations and the Placebo Effect

What you expect is often what you get, and the placebo effect is at work! We have noted elsewhere that one possible account for the engagement of the placebo effect is the wish to ‘please the physician’, to be a ‘good patient’. According to this Stanford study, this might come as only a few positive words. “… When a health care provider offers a few encouraging words about their patient’s recovery time from an allergic reaction, symptoms are significantly reduced.”

Similarly expectations about the benefit of exercise can be seen to actually impact on life expectancy outcomes. In this study “the team looked at death rates. They used statistical models to account for other factors linked to death, such as age, chronic illnesses, and body mass index (BMI). Even accounting for these risk factors, those who saw themselves as less physically active were 71% more likely to die in the 21 years following the original survey.”

Emerging Guidelines for Using Placebos in Clinical Practice

It is becoming increasingly clear that the placebo effect has a great influence on medical treatment. An international, interdisciplinary team of researchers led by Professor of Health Psychology Andrea Evers from Leiden University has now written a first set of guidelines on how to apply the placebo effect in clinical practice, published in Psychotherapy and Psychosomatics.

It was the result of the first official conference of the Society for Interdisciplinary Placebo Studies (SIPS), which was held in Leiden last year. During an interdisciplinary workshop led by Evers, a group of leading international researchers reached the consensus that knowledge about placebo and nocebo effects could lead to better treatment results with fewer side-effects. According to the researchers, it is crucial that patients receive more information about these effects, and that doctors receive training on the best doctor-patient communication to maximise placebo effects and minimise nocebo effects.

Read the full article here.

Patients may be experiencing placebo effect, but it’s still an effect: “Placebo is active treatment”

 

In Respect the Needle in OA (osteoarthritis),  a rheumatologist says:

“… Dealing with osteoarthritis, both patients and their physicians often have a hard time understanding what to make of novel “cures” such as platelet-rich plasma (PRP), stem cell treatments, and so-called prolotherapy.

Although these are typically marketed as halting or reversing joint degeneration in OA, there is virtually no evidence that they actually do. Yet it’s impossible to discount the countless reports from patients that the treatments helped them in terms of pain and function.

The explanation may very well lie in the placebo effect, said Joel Block, MD, a well-known osteoarthritis specialist at Rush University, speaking at the American College of Rheumatology’s 2018 State of the Art Symposium.

But the thrust of Block’s 30-minute talk can be summed up in two words: So what?

The placebo effect is still an effect and a very important one, he argued repeatedly in addressing current knowledge about therapies, largely unregulated, now marketed nationwide in newspapers and online as “disease-modifying.”

It’s “extraordinarily strong” in osteoarthritis, Block said, for reasons that aren’t entirely clear. The experience from randomized trials is that one normally expects a 40% response rate with placebo with large effect sizes. Moreover, the improvements in patient-reported pain do not quickly disappear: the trial data indicates that placebo responses last beyond a year, he said.

“Placebo is active treatment,” Block said.

Much Ado … About that New Antidepressant Study

A recent ‘meta-study’ claims that placebo are NOT, in fact, on par with conventional antidepressant medications, as we have reported numerous times in this blog. It seems, however, that this study should be read with certain caveats, most particularly that “The review’s authors have acknowledged that almost 80% of the studies they analysed had been funded by the pharmaceuticals industry.” (Fawning Coverage of New Antidepressants Review Masks Key Caveats) Confirmation bias, anyone?

Words Matter

We know that communication matters – in regard to any human exchange and any human relationship. We can also consider the words we use, and the way we use them, in relation to their value as ‘placebo’. The effectiveness (or ineffectiveness) of communication can generate a placebo (or nocebo) effect, evidenced very clearly in the way that health practitioners interact with their clients, as illustrated in this article in the Irish Times, “Doctors Say One Thing. Patients Often Hear Something Else”.

“How patients frame questions and how doctors frame advice is an important element in successful health communication. Behavioural economists describe a phenomenon known as loss aversion: as humans, we are primed to feel losses nearly twice as heavily as we appreciate gains.

So for actions that we perceive as risky, a health message that presents the lack of action as an even greater risk is more effective. However, for actions that we don’t see as especially risky, presenting the action itself as beneficial has been shown to produce a better behavioural response.”

PLACEBO AND FAKE SURGERY

Two thought-provoking articles relating the placebo effect to ‘sham surgery’, which has been canvassed in these pages previously.

In this meta-study, the authors point out that ” the literature is not chock full of studies comparing a surgical procedure to placebo. While the study of a drug versus placebo is standard practice, the picture changes radically when the placebo is a sham operation involving incisions and anesthesia …  Of about 3000 articles, 53 full-text articles were selected. They represented randomized controlled studies, with both an active intervention and a placebo arm involving a sham procedure. The authors defined a surgical outcome based on three elements:

•    The critical surgical component – the anatomic changes felt to result in a therapeutic effect

•    Placebo component – the patient’s expectations

•    Non-specific effects – changes in the natural history of an illness that might impact the outcome, the experience of being in a hospital, interactions with staff – the multitude of other factors.

In this study, the author admits that sham (placebo) srugery already occurs. Because it can work.

How?

“How can sham surgeries work? Bigness. In the same way that placebo pills and other modalities make people get better, the clinical evaluation, workup, stress and travel of surgery day, surgical prep, etc. all make for an almost unbeatable set of placebo-instituting conditions. And with some of the data which exist, sham surgeries perform better in the patients’ minds than a drug treatment that’s a comparator for the same condition.

Placebos and acupuncture

Here’s a link to a fascinating meta-analysis of the effectiveness of acupuncture in the treatment of chronic pain, controlling for some of the dodgy and unscientific ‘studies’ out there.

In this article, the outcomes of the study are listed and discussed, and it’s good news for acupuncturists.

‘When comparing legit acupuncture to standard care, there was a statistically significant benefit to acupuncture … “We saw a measurable effect there,” he explains. “If acupuncture were a drug, we’d say the drug works.”’

…and later, in relation to the placebo effect:

‘Many people equate placebo effects with scams. “The term placebo has always had this very negative connotation,” says Vitaly Napadow, director of the Center for Integrative Pain Neuroimaging at Harvard Medical School. But Napadow says our poor opinion of placebo needs revising. The human body has built-in systems for stoking or calming pain and other subjective sensations. “If a placebo can target and modulate these endogenous systems, that’s a good and a real thing,” he says.’

Meanwhile, in two comprehensive studies into the value of acupuncture treatment in treating women’s health issues, we see mixed results.

‘These studies shed new light on when and when not to consider using acupuncture,” Dr. Josephine Briggs and David Shurtleff, of the U.S. National Center for Complementary and Integrative Health, wrote in an editorial to accompany the studies.

The research done to date on acupuncture has shown that, generally, its benefits are limited to outcomes that are subjective, such as pain, Briggs and Shurtleff wrote. People’s positive expectations and the reassurance they feel from the procedure likely contribute to the benefits. “Clearly these ancient practices are helping reveal the complexity of the links between the mind and the body,” the editorial said.’