Tag Archives: Open Label Placebos

What’s in a placebo?

When is a placebo not a placebo? It seems that placebos are no as ‘unreactive’ as the literature would suggest. Research hastened and made more urgent by the rushed efforts to develop a Covid-19 vaccine have revealed the need to create a standard for the actual content/ingredients of the placebo used in a given trial.

This article claims that:

“Some researchers conducting clinical trials on a COVID-19 vaccine have not revealed to the public what the placebo contains, but they should. This is because the placebo ingredients influence how effective or harmful the active treatment, with which the placebo is compared, appears.”

Later, the article continues:

“Placebo controls are rightly the gold standard against which new treatments are measured. If a new treatment proves to be better than a placebo, it is taken to be effective. Otherwise, it isn’t. The problem is that until today, there has been no standard for placebos, which made estimates of side-effects confusing. Our new guideline fixes this problem by encouraging rigorous reporting of placebo ingredients.

We’ve known about the failure – and need – to report what’s in placebos for 15 years. By following the new guideline, we can get more accurate information about how beneficial and harmful treatments tested in placebo-controlled trials are.”

Here’s a study on ‘A guide and checklist for reporting placebo and sham controls’

‘Non deceptive’ placebo treatments

We have posted for a while now on so-called ‘open label’ placebos, and the placebo effect engaged when someone actually knows they’re taking a sugar pill (or any other placebo treatment such as a saline injection).

This report, in Science Alert, claims that “across two experiments (…) during a highly arousing negative picture viewing task, non-deceptive placebos reduce both a self-report and neural measure of emotional distress.”

It seems that ‘open label’ placebos can also be described as ‘non-deceptive placebos’. This designation is of importance where researchers try to tackle the ethical issues involved in ‘lying’ to people about the test drug (or non-drug) being administered.

The report is based on research published in the prestigious journal Nature, Placebos without deception reduce self-report and neural measures of emotional distress .

“What if someone took a side-effect free sugar pill twice a day after going through a short convincing video on the power of placebos and experienced reduced stress as a result?” says lead researcher and psychologist Darwin Guevarra from Michigan State University (MSU).

“These results raise that possibility.”

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.”

Open Label Placebos … again

An article in Big Think entitled People are knowingly taking placebos—and its working starts to untangle some of the theories about the functionality of ‘open label’ placebos – which describes the engagement of a placebo effect even when people know they’re taking a placebo. 

“Even though they were told that what they were taking was placebo and contained nothing of therapeutic value, those patients who received the placebo reported a 30% reduction in usual pain and maximum pain and a 29% drop in their disability. Incredibly, the placebo worked better than the real pain medication. Participants who took the pain pills reported feeling 9% less usual pain, and 16% less maximum pain. Furthermore, patients taking the real medication reported no change in their level of disability.”

Five myths about placebos

1. The placebo effect is all in the mind.

“In reality, placebo treatments can cause measurable, biological changes similar to those triggered by drugs.”

2. Placebos work only if patients think they’re real.

“Over the past few years, however, scientists have found that this isn’t true. Honest (‘open label’) placebos work, too.”

3. Neurotic, suggestible people are more likely to respond to placebos.

“It’s not neurotic people who see benefits … but rather those who are optimistic, altruistic, resilient and straightforward.”

4. You have to take a placebo to get a placebo effect.

“It’s true that placebos won’t shrink a tumor, cure an infection or replace insulin in someone with diabetes. But many “real” medical treatments — particularly those that modify symptoms like pain, fatigue, nausea or depression — rely on the placebo effect.”

5. Drugs are always more effective than placebos.

A rigorous recent study of 152 trials found that placebo effects are often about the same as drug effects.

For more detail on all of the above, and references to research, read the Washington Post article.

More on ‘Open Label’ Placebos

Open Label Placebos (OLPs) are becoming a Thing, reinforced once more by Ted Kaptchuk’s placebo research group at Harvard Medical School. This article – Open-Label Placebo (OLP): Take This, It Is A Sugar Pill, It Will Help You! – provides us with a succinct update on the current clinical research scene, including valuable reference to two meta-studies which attempt to summarise the current state of our understanding. Importantly, the writers note that formal studies to date “have shown that while openly-applied placebos affect symptoms (depression, motor activity, pain, fatigue, etc.), none have yet shown that it may also affect disease biomarkers. Secondly, patient (self-)selection has to be tested for biases, e.g., whether the recruited patients are prone to respond to placebo, while others not recruited are not. Last but not least, it would be important to know how OLP compares to effective drug treatment of the same condition and in the same patients.”

More Research on ‘Open Label’ Placebos

Whether you know you’re taking a placebo pill or not, it will still have a beneficial effect, new research has revealed (Is the rationale more important than deception? A randomized controlled trial of open-label placebo analgesia.)

Scientists from Harvard University and the University of Basel prescribed a group of minor burn victims with a “treatment” cream, telling only some of them that it was a placebo.

After the cream was applied, both groups reported benefits, despite the placebo cream containing no medicine.

Read the full article here

On the subject of Open Label Placebos, here’s a link to research on their efficacy in chronic lower-back pain.

Yes, the placebo effect is all in your mind. And it’s real.

It seems that the research on the placebo effect is broadening and deepening.

“Over the last several years, doctors noticed a mystifying trend: Fewer and fewer new pain drugs were getting through double-blind placebo control trials, the gold standard for testing a drug’s effectiveness.”

This recent article, which includes some useful links for further reading, points to the degree in which the placebo effect (classified by the writer as a ‘family of overlapping psychological phenomena’) is being studied and considered. The family of placebo effects ranges ‘from the common sense to some head scratchers’, and include:

1) Regression to the mean
2) Confirmation bias
3) Expectations and learning
4) Pharmacological conditioning (‘This is where things get a little weird’)
5) Social learning
6) A human connection

Interestingly, it seems that at least in pain studies, ‘there’s evidence that placebos actually release opioids in the brain’.

In another article in Mother Jones, What the Heck Is a Placebo Anyway?, the authors propose ‘… we now know that they (placebos) often involve real chemicals produced by the body—real drugs from your “internal pharmacy.” Some of these chemicals are used by the brain to make sure that your expectation meets reality. When expectation doesn’t meet reality, the brain steps in and forces it to fit.’

Over at Fox News (of all people), quoting the Wall Street Journal, they’re suggesting ‘Placebo drugs really work, evidence suggests‘.

Placebo ‘drugs’? Come on, folks, that misses the point a bit!

Placebos and surgery

“Certain types of elective surgery only benefit patients because of placebo effect, says Prof Andy Carr.”

We’ve posted on this previously, on the mater of ‘sham srugery’ for knee pain actually having a substantial impact on lessening pain. In this case, a senior orthopaedic surgeon in Britain, says “The correct thing has got to be to do … trials – not to continue doing operations where we don’t know whether or not there’s a strong placebo component or an entire placebo component because that means that tens or hundreds of thousands of patients are having unnecessary operations,” he said.

That’s right – ‘tens or hundreds of thousands’.

Another professor, also from Oxford, points out the opinion, which we have seen has been gathering momentum (and scientific respectablity) over the past couple of years, that ‘deception’ is not a requirement for the engagement of the placebo effect. “In the modern world where we’re trying to limit the amount of time physicians spend with patients we’re going in the opposite direction of what the science is telling us, which is that [expectation] is really important physiologically and therapeutically and we’re throwing that away.”

Read the whole Guardian article here.