Tag Archives: Research

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.

PLACEBOS and the immune response

Could brain stimulation slow cancer?

The idea is that ‘the placebo effect’ activates the same ‘Reward Circuit’ in the brain as that “activated by food, sex and social interactions (as well as gambling and addictive drugs)”. This in turn stimulates the immune system and generates ‘anti-tumor immunity’ against pathogens.

This is Scientific American, dear readers, and the claim is based on the kind of clinical experimentation that placebos are now inspiring. Placebo Studies!

“It’s like doing immunotherapy without medication.”

At the moment it’s just been shown in mice, and the ‘data are preliminary’, but even if it turns out only partly to be shown in humans, the implications are profound.

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.”

The Man Who Overdosed on Placebo

The Nocebo effect, dramatically illustrated …

Several years ago, a published case study describes a 26-year-old man who was taken to the emergency room. After arguing with his ex-girlfriend, he attempted suicide by swallowing 29 capsules of an experimental drug that he obtained from a clinical trial that was testing a new antidepressant. When he arrived at the hospital, he was sluggish, shaking, and sweating and had rapid breathing. His blood pressure was extremely low at 80/40, and his pulse was 110.

Doctors were successful at raising his blood pressure. Over the course of four hours, they injected him with 6 liters of saline solution. His blood pressure increased to 100/62, which is at the lower end of the normal range, but his pulse remained high at 106.

What finally cured the patient wasn’t anything the emergency room staff did. Instead, a doctor from the clinical trial arrived at the hospital. He told the patient that those antidepressant pills weren’t antidepressants because he had been randomized into the control arm of the trial. Yes, that’s right: He overdosed on placebos.

Oh.

Within 15 minutes, the patient’s blood pressure stabilized at 126/80, and his heart rate dropped to a perfectly normal 80 beats per minute.

Read the entire article here.

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?

Sex Differences in the Placebo Effect?

Do males and females respond differently to the placebo effect? This review of 18 studies concludes that “1) males responded more strongly to placebo treatment, and females responded more strongly to nocebo treatment, and 2) males responded with larger placebo effects induced by verbal information, and females responded with larger nocebo effects induced by conditioning procedures.”

Why?

It seems “that … differences in the placebo and nocebo effects (are) probably caused by sex differences in stress, anxiety, and the endogenous opioid system.”

Download the study ‘A systematic review of sex differences in the placebo and the nocebo effect’

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.”

Do Worms Experience A Placebo Effect?

No, seriously, do they?

“Is the placebo effect biologically real? We’re not sure. But, if it is, then it is safe to say that it evolved over time, that it confers some survival advantage, and most importantly, it should also be able to be seen in other organisms. It has been reported in rats on occasion. But, what if we could study the placebo effect in lower organisms like fruit flies (Drosophila melanogaster) or worms (Caenorhabditis elegans)?

In the study of aging, these tiny, but powerful animals who age quickly, make it easier to do many experiments in a shorter period of time. Worms, in particular, are a fantastic model for the field of dietary restriction (DR), a programmed method of reducing calorie intake and the most scientifically sound method of extending lifespan. But in worms, the extended lifespan offered through DR is disrupted by the smell of food which tricks their bodies out of DR mode and stops the extension of life.”

Check out  Simon C. Harvey, Chris J. Beedie, “Studying placebo effects in model organisms will help us understand them in humans” Biology Letters. 29 November 2017 or read the ACSH article here.

Placebos and anti-depressants in children and teenagers

A recent ‘meta-analysis’ of the placebo effect on the use of anti-depressants in children and adolescents (shudder …), based on data from trials involving more than 6,500 children and adolescents up to the age of 18, has been published by the University of Basel and Harvard Medical School and published in the journal ‘JAMA Psychiatry’.

The most common mental disorders in children and adolescents include anxiety disorders, depressive disorders, obsessive-compulsive disorder, and post-traumatic stress disorder.

“The results of the meta-analysis show that, although antidepressants work significantly better than placebos across the range of disorders, the difference is small and varies according to the type of mental disorder. However, the results also showed that the placebo effect played a significant role in the efficacy of antidepressants. The study also found that patients treated with antidepressants complained of greater side effects than those who received a placebo. The side effects included everything from mild symptoms such as headaches to suicidal behavior.”

‘Suicidal behaviour’ as a ‘side effect’ … Really?

Consistent with other posts through this blog, the analysis also shows that the placebo effect is stronger in cases of depression.