Placebo Effect Has Risen Among Americans, Making Drug Development More Difficult

By Dr. Mercola

By definition, a placebo is an inert substance that has no effect on your body. In medical research, placebos (such as sugar pills) are used as controls against which the effects of drugs are measured.

However, the placebo-effect, in which a patient believes he or she is getting an actual drug and subsequently feels better despite receiving no "active" treatment at all, has become a well-recognized phenomenon.

Researchers have found that placebos can work just as well as potent drugs, and studies into the placebo effect have also shown that many conventional treatments "work" because of the placebo effect and little else.

What's more, recent investigations reveal the placebo effect is growing in potency — but only among Americans! This is an intriguing mystery that as of yet has no solid explanation, and it's having a dramatic impact on the development of new painkillers.

Growing Placebo Effect in US Thwarts Painkiller Development

As recently reported by Scientific American¹ and Forbes,² drug companies are finding it increasingly difficult to get pain-reducing drugs through clinical trials, but not because the drugs are necessarily getting worse.

Instead, they're finding that people's responses to placebos are getting stronger, and this is making it more difficult to prove a drug's advantage. According to Scientific American:

"The change in response to placebo treatments for pain, discovered by researchers in Canada, holds true only for US clinical trials. 'We were absolutely floored when we found out,' says Jeffrey Mogil, who directs the pain-genetics lab at McGill University in Montreal and led the analysis. ³

Simply being in a US trial and receiving sham treatment now seems to relieve pain almost as effectively as many promising new drugs."

Previous research has noted that the placebo response appears to be increasing in trials involving antidepressants and antipsychotics. Here, the placebo effect is rising across the world, not just in the US, which adds another layer to the mystery.

It was such findings that prompted researchers to investigate the strength of the placebo response in painkiller trials, because over the past decade more than 90 percent of drugs aimed at chronic pain have failed to show efficacy in clinical trials, suggesting something odd might be afoot.

A Patient's Expectations May Be Paramount to Treatment Success

In all, Mogil's team reviewed 84 clinical trials of drugs designed either for the treatment of chronic neuropathic pain or cancer pain, published between 1990 and 2013.

Interestingly, while the subjects' ratings of the effect of the drugs tested remained stable across the 23-year period, placebo responses significantly grew.

In 1996, pain-relieving drugs were on average 27 percent more effective for pain relief compared to placebos. By 2013, the placebo response had risen to the point that drugs were only measuring as being 9 percent more effective. Even more interesting, this pattern was only found in American trials.

No major changes in placebo response were found in trials conducted in Europe, Asia, and other countries. How could this be? As reported by Scientific American:⁴

"One possible explanation is that direct-to-consumer advertising for drugs — allowed only in the United States and New Zealand — has increased people's expectations of the benefits of drugs, creating stronger placebo effects.

But Mogil's results hint at another factor. 'Our data suggest that the longer a trial is and the bigger a trial is, the bigger the placebo is going to be,' he says. Longer, bigger US trials probably cost more, and the glamour and gloss of their presentation might indirectly enhance patients' expectations, Mogil speculates.

Some larger US trials also use contract research organizations that can employ nurses who are dedicated to the trial patients, he adds — giving patients a very different experience compared to those who take part in a small trial run by an academic lab..."

Results Challenge Conventional View of How Drugs Work

Another interesting side-effect of these findings is the fact that it challenges the very foundation upon which placebo-controlled trials are built. The principle here is that when you compare a drug against a placebo, the results will reveal how well the drug works.

In essence, it's recognized that the total response to a drug contains two parts: the placebo effect plus the actual biochemical impact of the drug. The difference noted between the placebo and the drug then tells you the effectiveness of the biochemical portion. At least that's been the prevailing theory.

However, these findings reveal that this may not be entirely correct, because while placebo responses have risen, the drug responses have not risen in equal measure, which should happen if the formula of "placebo response plus drug response equals total response" was true.

Even more remarkable are studies showing that the placebo effect is also at work in animals. Indeed, researchers have found rats experience placebo-induced pain relief^5,6 for example.

To demonstrate this, rats were injected with morphine two times, which preconditioned them to expect pain relief in conjunction with an injection. Then, when the morphine was traded for saline, as many as 40 percent of the rats responded with signs of pain relief, as if they'd been given morphine.

They've also found that when a placebo procedure is stressful or painful, such as an injection, it will impact the animal's response.⁷

Hence whenever stressful procedures are part of the study design, a control group of completely untreated animals should be included, in addition to the group getting the actual drug injected, and the group getting a placebo injection.

Epileptic dogs have also been shown to respond to placebo, actually experiencing a decrease in seizure frequency in response to sham drugs!⁸

Harnessing Placebo Effect May Be Part of Future Medicine

According to Mogil, it would be worth finding out how the placebo response is being generated among Americans, and then add those elements to standard patient care, rather than redoubling efforts to create more effective drugs. This might include a stronger relationship between patient and nurse, for example. Professor Ted Kaptchuk, director of Placebo Research at Harvard Medical School in Boston, agrees, stating:

"If the major component of a drug in any particular condition is its placebo component, we need to develop non-pharmacological interventions as a first-line response."

Kaptchuk recently published a paper suggesting medicine could in fact be improved simply by harnessing and taking full advantage of the placebo effect. His paper notes that since the placebo effect is rooted in neurobiology, it could be a valuable form of treatment in and of itself. Professor Kaptchuk told Medical News Today:⁹

"Placebos don't necessarily provide cures, but they provide relief. In medical situations in which no cure is available, supportive and attentive health care can help patients to feel better, and when effective drugs do exist, placebo effects can enhance their impact. A significant body of research has resulted in a shift from thinking of placebos as just 'dummy' treatments to recognizing that placebo effects encompass numerous aspects of the health care experience and are central to medicine and patient care."

Indeed, a placebo does produce a number of changes in your brain, which help explain how a sugar pill can produce an effect even without biochemically active ingredients. For example, the placebo effect has been noted in treatments for depression, headaches, and degenerative meniscal tears, just to name a few. Interestingly, previous research has shown that the placebo effect can produce marked effects even when no deception is involved at all.

In one trial, nearly 60 percent of patients given a placebo pill, who were told they were receiving a placebo, reported adequate relief from irritable bowel syndrome (IBS) symptoms. Only 35 percent of those who received no treatment at all reported adequate relief.

What Makes the Placebo Effect Work?

The jury is still out on the exact mechanisms that make the placebo effect so effective. It does appear that simply going through the ritual of treatment is enough to cause a beneficial response in many cases. Regardless of the mechanism, studies show that if you think you're receiving a treatment, and you expect that treatment to work, it often will. A previous article in Scientific American¹⁰ noted that:

"Placebo effects can arise not only from a conscious belief in a drug but also from subconscious associations between recovery and the experience of being treated — from the pinch of a shot to a doctor's white coat. Such subliminal conditioning can control bodily processes of which we are unaware, such as immune responses and the release of hormones."

This was demonstrated in a study¹¹ published earlier this year, which found that people with back pain who believe or expect that acupuncture might be helpful actually get more pain relief from it, compared to those who do not believe it will work. According to study author Felicity Bishop, PhD:

"People who started out with very low expectations of acupuncture, who thought it probably would not help them, were more likely to report less benefit as treatment went on."

Research,¹² has also shown that your emotions and/or expectations can significantly influence the perceived intensity of pain. Positive expectations and emotions tend to minimize pain, while negative emotions such as fear tend to exacerbate it. This is an aspect of pain that has been exploited by torturers throughout human history.

Sham Surgery Trial Proves Knee Surgeries Are a $4 Billion Medical Hoax

Many are quick to say that the placebo effect is responsible for the benefits of alternative treatments and natural supplements — the implication being that the treatment doesn't really work, and any benefit is "all in your head." But few stop to consider the fact that many of the benefits of conventional drugs and other interventions are also due to the placebo effect. One of the most dramatic examples of this was a knee surgery study¹³ published in the New England Journal of Medicine in 2002. 

Not only does this double-blind, placebo-controlled, and multi-center trial definitively prove the power of your mind in healing, it also reveals that most knee surgery for osteoarthritis is an utter waste of money. The results of this study show that it's not actually the surgery itself that is responsible for the improvement, but rather it's almost entirely due to the placebo effect! More precisely, it's the ability of your brain to produce healing when you believe it should be happening (such as after you receive knee surgery). According to the authors:

"In this controlled trial involving patients with osteoarthritis of the knee, the outcomes after arthroscopic lavage or arthroscopic débridement were no better than those after a placebo procedure."

This was followed by another study,¹⁴ published in 2013, which also found that arthroscopic knee surgery for degenerative meniscal tears had no more benefit than "sham surgery." Here, they even excluded people with knee arthritis, as they tend not to benefit as much from meniscus surgery anyway, and the researchers wanted to ascertain if the surgery helps under "ideal circumstances."

Well, at the post-operative one-year mark, all patients, regardless of whether they had real or sham surgery, reported equal amounts of pain reduction, which led the researchers to conclude that real knee surgery offers no better outcome than sham surgery (placebo). This is a significant concession, as arthroscopic surgery on the meniscus is the most common orthopedic procedure in the US. According to this study, it's performed about 700,000 times a year to the tune of $4 billion.

But according to these findings, any surgeon who tells you this is "the best" or "only" option for your osteoarthritic knee pain will not have a leg to stand on when you show him or her this evidence. It's also worth considering these kinds of findings when you're weighing your treatment options. Remembering that your mind is the real healer here may help you find safer and less costly alternatives.

More Than 50 Percent of Pain-Relief from One Migraine Drug Is Due to Placebo Effect

Another example that reveals the extent to which the placebo effect may be at work in modern medicine is a study¹⁵ involving the migraine drug Maxalt (rizatriptan). When patients received placebo pills labeled as Maxalt, they reported similar pain relief as those receiving actual Maxalt tablets marked as placebo. According to the authors, the placebo effect accounted for more than 50 percent of the therapeutic value of this drug. Professor Ted Kaptchuk co-authored this study as well, and here he noted that:¹⁶

"This study untangled and reassembled the clinical effects of placebo and medication in a unique manner. Very few, if any, experiments have compared the effectiveness of medication under different degrees of information in a naturally recurring disease. Our discovery showing that subjects' reports of pain were nearly identical when they were told that an active drug was a placebo as when they were told that a placebo was an active drug demonstrates that the placebo effect is an unacknowledged partner for powerful medications." [Emphasis mine]

Harnessing the Placebo Effect with the Help of EFT

There may be cases in your own life where you can use your mind to help heal your body or reduce your reliance on conventional medical care, including medications. If you strongly believe you will benefit from something, you radically increase the chances that you will. But there is one caveat: you may need to resolve any emotional blocks that are standing in your way first.

Such a block could be the belief that the pain or illness cannot go away. Maybe a parent or relative had the same problem and they never recovered, so you probably "can't" get rid of it either. Another block could be resentment that you have the disease or the pain, or even an unconscious desire to keep your ailment because of the extra attention you gain from it.

The Emotional Freedom Techniques (EFT) is a powerful tool for getting to the root of emotional conflicts, allowing you to release them and help open your mind to the power of the placebo effect. EFT is one form of energy psychology and there are many derivatives that work, it is merely the most popular one out there and the one I am most familiar with. This non-invasive technique can also provide more direct relief for certain problems. For example, EFT has been shown to cut the frequency of tension headaches down by half, as well as reducing the intensity of the headaches.

EFT has been studied in more than 10 countries, by more than 60 investigators, with results published in more than 20 different peer-reviewed journals. In 2012, a critical review in the American Psychological Association's (APA) journal Review of General Psychology¹⁷ found that EFT "consistently demonstrated strong effect sizes and other positive statistical results that far exceed chance after relatively few treatment sessions."

This brought EFT one step closer to meeting the criteria for evidence-based treatments proposed by the APA, an important step toward EFT's acceptance by the wider professional community, and one that will bring its benefits to a wider group of people. The review found statistically significant benefits in using EFT for the following conditions:

Anxiety	Athletic Performance	Depression	Pain & Physical Symptoms
Phobias	Post Traumatic Stress Disorder (PTSD)	Weight Loss	Food Cravings

The Placebo Effect Is Real, and Can Be a Powerful Healing Ally

There's no denying that the placebo effect is real, and this is actually good news. It reveals you hold a great deal of power of healing within yourself — a power that can be tapped through belief and positive expectations. In my view, accepting the placebo effect, and recognizing this inherent self-healing power of the mind, can go a long way toward improving health care.

It can also make it a lot safer, as most drugs are riddled with dangerous side effects. Why take that risk if the equivalent of a sugar pill is just as effective? Overall, studies into the power of placebos show that in many cases healing comes in response to treatment — virtually any treatment, as long as it is given in such a way as to make you feel that you're being cared for and that your issue is being addressed.

This suggests doctors and hospitals could potentially start seeing better results simply by taking the time to show they care; to act in a personalized and compassionate manner. In essence, by improving the relationship between patient and care giver, many treatments might become more effective in response to the placebo effect of feeling supported and believing you can and will get better.