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The question of whether the placebo effect is getting stronger is complex. While some studies suggest that the effect may not be as robust in certain contexts, others highlight the significant role of psychological factors in enhancing the placebo response. The evolving understanding of the placebo effect underscores the importance of considering both historical data and recent findings to appreciate its multifaceted nature. Further research is needed to elucidate the mechanisms underlying the placebo effect and to determine the conditions under which it is most effective.

The placebo effect, a phenomenon where patients experience real changes in their health after receiving a treatment with no therapeutic value, has been a subject of scientific inquiry for decades. Initially quantified by Henry K. Beecher in 1955, the placebo effect has been considered a significant factor in clinical outcomes. However, recent studies have questioned the robustness and mechanisms of this effect. This article explores whether the placebo effect is indeed getting stronger or if our understanding of it is evolving.

Historical Perspective

Henry K. Beecher's seminal work, "The Powerful Placebo," published in 1955, claimed that 35% of patients across 15 trials experienced satisfactory relief from placebos alone1. This study laid the foundation for the scientific acceptance of the placebo effect. However, a reanalysis of Beecher's data revealed no substantial evidence supporting his claims. The improvements observed in patients could be attributed to various other factors such as spontaneous improvement, symptom fluctuation, and additional treatments, rather than the placebo effect itself1.

Recent Findings

Recent research has provided mixed results regarding the efficacy and strength of the placebo effect. For instance, a study investigating the impact of placebo and open-label placebo (OLP) treatments on strength, voluntary activation, and neuromuscular fatigue found minimal influence on these parameters. While energy levels increased following treatments, there was no significant effect on strength or fatigue resistance2. This suggests that the placebo effect may not be as potent in certain physical performance contexts, especially in untrained individuals. Conversely, another study demonstrated that placebos could significantly enhance muscle work and reduce perceived muscle fatigue when participants believed they were ingesting a high dose of caffeine3. This effect was even more pronounced when a conditioning procedure was employed, indicating that learning and expectation play crucial roles in the placebo response3.

Mechanisms and Modulation

The variability in placebo responses can be attributed to several factors, including psychological and neurobiological mechanisms. The top-down influence of cognitive processes, such as expectation and conditioning, appears to modulate the placebo effect significantly. For example, the belief that one is receiving an effective treatment can activate brain regions associated with pain relief and reward, thereby producing real physiological changes3.

Is the placebo effect getting stronger?

Michael Bennett has answered Unlikely An expert from UNSW Sydney in Epidemiology

There is indeed some evidence from the US that - at least in the field of pain medicine - the response in the placebo arm of trials is growing. For the moment, there is little evidence from other countries.

A number of suggestions have been made to explain this phenomenon. One explanation may be that new drugs being tested today are less effective than they used to and so the response to a placebo is closer to that for 'real' drugs than it used to be. This may be part of the answer, but is unlikely to be the whole answer as there is some evidence that the absolute rate of response to placebo also seems to be rising as well as the relative response.

(1) A second potential explanation lies in the nature of drug advertising in the USA. This suggests the open advertising direct to the public increases faith in medicine and so when taking a blinded placebo, there is a psychological bias toward greater effects than there used to be. An addendum to this suggestion is that the recent increased discussion in the public about placebo may actually mean that the public is better disposed to the concept of the placebo and more accepting that such preparations may produce benefits. This may indeed be part of the reason for the observed phenomenon of patients electing to continue taking a known placebo after the end of clinical trials.

(2) Finally, my own suggestion is that improved trial methodology over the last 20 or so years has eliminated many biases previously present in research and that this has had the effect of reducing the apparent effectiveness of 'real' drugs, while better blinding and concealment of allocation has allowed the full placebo effect to be measured in more recent trials. In any case, an interesting question and a fascinating phenomenon. Given how little we really know about the true nature of the placebo effect, how it may change over time is even harder to be sure about.

Is the placebo effect getting stronger?

Alexander Tuttle has answered Near Certain An expert from University of North Carolina in Neuroscience

Although it is possible to measure the placebo effect in controlled laboratory settings, many additional factors can influence an individual’s “response” to a placebo stimulus. These additional factors include social support, attention, medical knowledge, current mood, personal beliefs, or spontaneous resolution of symptoms (i.e., the individual gets better on his/her own without medical aid). As your question pertains to drug trial design, a better question would be: “Is the placebo response getting more pronounced over time in drug trials?”

The best way to answer this question is to look at published drug trial data for specific medical conditions. To determine if a new drug is effective, a randomized controlled trial (RCT) will typically compare patient response to an experimental drug versus patient response to a placebo treatment. By subtracting the response of the placebo group from the experimental group, this trial design uses the difference between groups to determine the unique effects of the drug AFTER accounting for any benefit from a general placebo response.

Several “meta” studies have tried to answer the placebo response question by looking at results from many published RCTs and seeing if the difference between groups is decreasing over time. Interestingly, meta studies looking at antipsychotics, antidepressants, and statins have shown that there are decreasing differences between drug and placebo groups over time. Furthermore, these meta studies determined that the decreasing difference between control and experimental drug groups is due to an increased placebo response, versus a decreased effect of the experimental drugs.

In a recently published study we applied similar meta-analytic strategies to see if placebo responses were becoming more pronounced over time (Tuttle et al., 2015). To compile our data, we went through hundreds of RCTs that used chronic neuropathic pain patients to test new pain-relief drugs. We selected 84 trials that were published over the past 25 years that met our inclusion criteria, pulled out patient data in both placebo and drug groups and compared responses over time. What we found was very interesting!

First, the difference between placebo and drug groups is decreasing over time.

Second, the smaller difference between drug and placebo groups is accounted for by an INCREASING placebo response in more recent trials. Third, the increasing placebo response is only occurring in RCTs conducted in the United States. However, since the majority of drug trials are conducted in the U.S., we found that this country-specific effect is driving the overall trend for an increasing placebo response in neuropathic pain drug studies.

Although our study isn’t sufficient to explain the reason why people in the U.S. are unique in their increasing placebo responses in drug trials, our findings are similar to other meta-analytic studies that have found increasing placebo responses in drug trials for antipsychotics and antidepressants. We speculate that the US is unique in its societal views about drugs and their ability to cure almost any condition. These strong beliefs in “the power of the pill” may be driven in part by constant pharmaceutical advertising to potential study participants (drug companies in the US are allowed to advertise their drugs directly to consumers). However, further research is needed to replicate a “US-specific” effect in other drug trials, as well as systematically determine why the US placebo response is increasing over time.

Is the placebo effect getting stronger?

Stewart Justman has answered Unlikely An expert from University of Montana in Medicine

I don’t think the placebo effect per se is “getting stronger.” In some clinical trials the test drugs have indeed been showing less superiority to placebo (as noted by other commentators), but in such cases it may be that the apparent increase of the placebo effect correlates with “richer social support,” more intensive clinical attention, longer trials, or the like. The placebo effect is not getting stronger in the sense that it can do things it couldn’t previously do, such as reverse disease processes.  In some cases, too, the placebo effect may wear off over time, which is perhaps what drives many patients to switch from one antidepressant to another and then another.

Despite general fascination with the placebo effect, I believe it’s important not to get carried away with it. I think of the placebo effect as an adjunct or by-product of the practice of good medicine, not as a trick the doctor can pull out of bag or a magical pharmacy residing inside us.

Is the placebo effect getting stronger?

Muhammad Hammami has answered Extremely Unlikely An expert from King Faisal Specialist Hospital & Research Center in Medicine

The placebo effect NOW has a "name, is better measured, and is more talked about, but there is no evidence that its getting stronger. Not including changes related to regression to the mean, natural history, Howthern effect, etc, under the placebo effect (the meaning effect), an important and correct current move, would in fact weaken the apparent "placebo" effect. Theoritically, the placebo effect is part of human nature that would not be expected to change.

Is the placebo effect getting stronger?

Graham Lappin has answered Unlikely An expert from University of Lincoln in Pharmacology, Drug Use, Toxicology, Biochemistry, Nutrition

This is a tricky question to answer as it depends upon what is meant by the placebo effect. In a literal sense the answer is no, because by definition a placebo has no pharmacologic action. I have seen several internet sites that claim the placebo effect is increasing but this is really based on a rather simplistic approach. Putting the pharmacology to one side, two other factors need to be considered.

1) there has been much interest in the placebo effect in recent years and there's the old adage that the more you look for something the more you find. It is a complex phenomenon, largely psychological but it can influence the body's physiology https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013051/

2) the strength of the placebo effect can be influenced by external factors (see the above link) and if those external factors change, so will the placebo effect. Where doctors, for example, take a more intense interest in their patients.

Is the placebo effect getting stronger?

Sergio  Halsband has answered Likely An expert from Association of Argentine Psychiatrists (APSA)  in Psychology

I think placebo effect is getting stronger because new drugs have less side effects and patients cannot distinguish if they are taking placebo or not. In depression the placebo effevt of antidepressants is very high.

Is the placebo effect getting stronger?

Seetal Dodd has answered Extremely Unlikely An expert from University Hospital Geelong in Pharmacology, Pharmaceutics

The answer to whether the placebo effect is "getting stronger" depends on what you mean by this question. I have taken this question literally and therefore my answer is 'no'. A placebo is inert. It cannot become 'more inert'. Alternatively, it could be argued that the placebo effect is "getting stronger" if people were becoming more susceptible to the placebo effect, however there is no evidence that people have changed in this regard.

The likely back-story for this fact-check is that many clinical trials of pharmaceutical agents unexpectedly fail to show statistically significant separation between placebo and active study arms, and there is a view that failed drug trials are becoming more and more common. While it may be true that many drug trials unexpectedly fail, this cannot be due to a stronger placebo effect. Other factors, especially those associated with the study population or study design should be investigated as causes of clinical trial failures.

Is the placebo effect getting stronger?

Pete Trimmer has answered Unlikely An expert from University of California, Davis in Psychology

From a theoretical perspective, the strength of placebo effects will depend on two main factors: 1) the expectations of patients and 2) the amount of control that patients can actually exert over an ailment (without which, expectations will not affect things).

Let's assume that we're dealing with a condition where the amount of effort put in by a patient (including their sub-conscious physiology) will positively affect outcomes, and that we're measuring 'real' outcomes, rather than just patients' perceptions of outcomes (which is a related rabbit-hole!). If people come to believe that they should not put (much) effort into getting well until particular conditions prevail, then any placebo that makes those conditions appear will tend to have a large effect. As such expectations can come through societal (cultural) beliefs, it's entirely possible that the strength of placebo effects could increase, or decrease, in different cultures over time. Indeed, from a theoretical perspective, we'd expect the effect to alter with time, though it's very difficult to predict the direction of effects. Whether the effect is actually increasing (or decreasing) significantly at present is an empirical question, which I don't have an answer to.

In case the above seemed rather abstract, as an example, we could imagine testing an old-school homeopathic treatment (by 'old-school', I mean where there is still some type of ingredient in the mix, rather than having been watered down to effectively zero) on a particular condition. Let's assume for instance that the 'active' ingredient in the mix does have some small positive effect, and that there has historically been some placebo effect of the treatment too, so outcomes were a mix of both effects. With the current push in the media of discrediting homeopathic treatments, the placebo part of the effect may be reduced. Or, on the flip-side, when a new medical 'treatment' is advertised (e.g., some tablet for reducing swelling), it's possible that the belief level of the population in such treatments will influence the size of its effect.

Is the placebo effect getting stronger?

Andrew Moore has answered Unlikely An expert from Oxford University in Neuroscience

My response is necessarily largely restricted to my area of expertise, namely pain.

However, there are a few basic issues to bear in mind:

1. There are a lot of studies in experimental situations, often on volunteers, and sometimes backed by things like fNMR, suggesting that short-term messing with the mind can induce placebo effects. That may be true, but this is not true placebo (doing nothing), but an intervention of a different sort. The effects are time limited (important when extrapolating to chronic conditions), and studies are small (which is a worry as small studies are known to be potentially biased). The implications for real-life situations is probably close to zero.

2. Other way of examining placebo effects is to look at clinical trial data. The issues here are many. First and probably most important is what question is being asked – the outcome. There is very good evidence in pain that the higher the hurdle for response, the lower the response seen with placebo. Another is case-mix, with more recent, large studies tending to recruit people who are or may be different from those in smaller academic studies from the past – a primary care rather than secondary care mix. There is also emerging evidence that in some parts of the world, particularly the USA, people entering trials are “professional patients” who do not provide full medical history to get into trials, do not take the medicines, and who may be in more than one trial at the same time. In addition, there is often a tendency to conflate different types of a condition – most are a spectrum of disorder, and for instance in chronic neuropathic pain, different types have different placebo responses. There are other issues as well, but taken all things together, trying to tell whether things have changed over time is hard because we don’t always compare like with like.

3. This might explain, for instance, why a group from McGill were able to conclude that "Increasing placebo responses over time in U.S. clinical trials of neuropathic pain” - but not European trials or those conducted in other places.

4. One circumstance where like can be compared with like is acute pain trials – looking at pain after surgery, where trial methods have been pretty constant for decades, and where outcomes are standardised. In a large analysis of all high-quality trial data colleagues and I were able to show a consistent decline in placebo response rates over time (this is submitted to a journal).

5. Other studies show no change over time.

The evidence of major changes in placebo response over time is at best not proven.

Is the placebo effect getting stronger?

Emmanuel Pothos has answered Unlikely An expert from Tufts University in Pharmacology, Neuroscience

It is not clear if the placebo effect is getting stronger and how to properly measure the strength of the placebo response across different patients, disorders, medications and lifestyle interventions. However, it is clear that the placebo effect is certainly being reported more thoroughly since clinical trials for new medications introduced a placebo arm component. It is also clear that

there are more efforts nowadays to understand the placebo effect in scientific terms and identify the cellular and molecular mechanisms in the brain that drive the strength of the placebo response. The more accurate reporting of the placebo effect for several therapeutic drugs and different patients may very well convey the impression that the placebo effect is getting stronger; but it may be the case that the placebo effect has always been there but only now we begin to understand it in more scientific terms and may be able to determine criteria for predicting who will and who will not be a strong placebo responder.

Is the placebo effect getting stronger?

Stewart Justman has answered Unlikely An expert from University of Montana in Behavioural Science

I don’t think the placebo effect per se is “getting stronger.” In some clinical trials the test drugs have indeed been showing less superiority to placebo, but in such cases it may be that the apparent increase of the placebo effect correlates with “richer social support,” more intensive clinical attention, longer trials, or the like. The placebo effect is not getting stronger in the sense that it can do things it couldn’t previously do, such as reverse disease processes. In some cases, too, the placebo effect may wear off over time, which is perhaps what drives many patients to switch from one antidepressant to another and then another.

Despite perennial fascination with the placebo effect, I believe it’s important not to get carried away with it. I think of the placebo effect as an adjunct or by-product of the practice of good medicine, not as a trick the doctor can pull out of bag or a magical pharmacy inside us.

Is the placebo effect getting stronger?

Jeremy Howick has answered Likely An expert from Oxford University in Philosophy, Epidemiology The placebo effect seems to be getting stronger, especially in the United States.

Is the placebo effect getting stronger?

Pekka Louhiala has answered Unlikely An expert from University of Helsinki in Health

There’s a problem with the question: There is not a single entity called ”the placebo effect”. Instead there are many psychological and physiological mechanism behind so-called placebo effects (in plural). Also 'placebo effects' in clinical trials and 'placebo effects’ in clinical medicine are two different worlds.

In a very narrow sense the question may be meaningful: if we look at the trials on anti-depressants, for example, the general wisdom has been that placebo effects have become stronger. A recent analysis showed, however, that they have been stable for over 25 years (https://www.ncbi.nlm.nih.gov/pubmed/27726982)

Is the placebo effect getting stronger?

Daniel Moerman has answered Near Certain An expert from University of Michigan, Dearborn in Anthropology

The evidence for this comes from comparisons of rcts done similarly over a period of time. The first, and clearest, case comes from a paper about 2000 which showed that the "placebo control groups" in studies of several kinds of antidepressants had increased over a 20 year period from the late 70s until about 2000. (Walsh, B. T., Seidman, S. N., Sysko, R., & Gould, M. (2002). Placebo response in studies of major depression: variable, substantial, and growing. JAMA, 287(14), 1840-1847.) It was quite clear.

More recent studies of control groups in antidepressant studies show less, or no increase since about 2000. But these control group rates are today in the 60 to 70% improvement range. They can't get much better than that! In the 1970s, the only known effective treatment for depression was electric shock therapy. No one believed that pills could do the job. By now, a generation after "Listening to Prozac" and a thousand shows with Oprah, "everyone knows" that pills can "cure" depression. While it's strange and curious to think that control group rates can increase over time, remember that whatever is going on in the people in the control group, the same thing is probably happening in the active treatment group. So, if placebo treatment rates have increased, so have drug treatment rates. What we know, think and understand about medicine affects us all, regardless of what the precise treatment is.

Is the placebo effect getting stronger?

Fabrizio Benedetti has answered Likely An expert from University of Turin in Neuroscience

There is some compelling evidence that placebo responses are getting stronger across a number of psychiatric disorders and pain.

Is the placebo effect getting stronger?

Morton Tavel has answered Extremely Unlikely An expert from Indiana University School of Medicine in Medicine, Cardiology

IS THE PLACEBO EFFECT GETTING STRONGER? ANSWER: There is no credible evidence that this effect has changed over time, but this assessment is confounded by the vast number of variables involved (1,2).

First, the conditions being treated produce highly variable placebo responses: Subjective complaints such as depression, pain or fatigue are far more susceptible to placebos than objective conditions such as cancer or neurological degeneration (e.g. Parkinson's disease, etc.).

Second, the means' that placebos are applied produce variable responses: Active contacts between care-givers and subjects, as exemplified by surgical procedures, sham injections, or acupuncture, exhibit magnified placebo responses in comparison with the mere administration of “dummy” placebo pills. Moreover, all placebo responses are enhanced by positive and upbeat attitudes displayed by the caregiver him/herself (the so-called “placebo personality”), which is usually coupled with lengthy explanations of expected improvement.

All these confounding variables render accurate comparisons of placebo effects over time virtually impossible. I would simply conclude that the placebo effect is often quite powerful and will remain with humanity permanently, to be used to benefit the ill by honest healers, but, unfortunately, too often by scam artists and quacks, who are most effective in exploiting unwary or gullible subjects for financial gain.

1 Tavel, ME, “Snake Oil is Alive and Well: The Clash between Myths and Reality. “Reflections of a Physician”. Brighton Press, Inc. Chandler, Arizona, 2012

2 Tavel ME. The Placebo Effect: The Good, The Bad, and The Ugly. The American Journal of Medicine. 2014; 127(6):484–488

Is the placebo effect getting stronger?

Arif Khan has answered Near Certain An expert from Duke University in Pharmacology

This of course depends on whether the question is really asking about the "placebo effect" or the "placebo response." The placebo response is an experimental measurement of nonspecific, non-pharmacological changes that occur after a specific treatment begins. When one refers to the "placebo effect" they are usually referring to the assumed processes that contribute to non-specific symptom improvement, including the reduction of stress, contact with an expert healer, the expectation of improvement, and increased attention and behavioral orientation towards their condition.

While the placebo effect is not able to be directly measured, the placebo response can be. Empirical evidence regarding the placebo response in clinical trials of various sorts (see citations below) shows that the placebo response has increased dramatically in the past several decades, although it has started to slow down. Correspondingly, the drug effect has increased; the assumption being that the portion of the drug response that is actually accounted for by placebo is responsible for this increase. While there are certainly factors of measurement and the experimental condition itself that may contribute to this observed rise in the placebo response across conditions, it also stands that there is unexplained variance still in the magnitude of placebo response. This means that the rise in placebo response is not fully explained by methodological and statistical treatment of trial data. Patients in clinical trials are definitely more likely to respond with greater symptom reduction when given placebo pill than they were in decades past.

So if the question is asking about improvement in patients treated with the nonpharmacological effects of taking placebo pill, then the answer in undeniably yes, the placebo effect is increasing. If the question is asking about the influence of certain processes contributing to placebo response, such as expectancy, then it seems likely that these forces have increased, but there is no way to directly measure such an increase in the contribution of these individual processes.

Khan A, Fahl Mar K, Faucett J, Khan Shilling S, Brown WA. Has the rising placebo response impacted antidepressant clinical trial outcomes? Data from the Food and Drug Administration 1987-2013.World Psychiatry, 2017;16(2):181-192.

Khan A, Fahl Mar K, Brown WA. Does the increasing magnitude of placebo response affect outcome of adult and pediatric ADHD clinical trials? Journal of Psychiatric Research, 2017;94:202-207.

Khan A, Fahl Mar K, Schilling J, Brown WA. Magnitude and pattern of placebo response in clinical trials of antiepileptic medications: Data from the Food and Drug Administration 1996 - 2016. Contemporary Clinical Trials, 2017;64:95-100.

Khan A, Fahl Mar K, Schilling J, Brown WA. Magnitude and pattern of placebo response in clinical trials of oral antihyperglycemic agents: Data from the Food and Drug Administration 1999 – 2015. Diabetes Care, 2018;41(5):994-1000.

Khan A, Fahl Mar K, Schilling J, Brown WA. Does the rising placebo response impact antihypertensive clinical trial outcomes? An analysis of Food and Drug Administration data 1990-2016. PLoS One, Feb 28, 2018; https://doi.org/10.1371/journal.pone.0193043