Placebo Effect Has Risen Among
Americans, Making Drug Development More Difficult
October 22, 2015
Story at-a-glance
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A placebo is an inert substance that has no effect
on your body. In medical research, placebos are used
as controls against which the effects of drugs are
measured
In US trials, people’s response to placebos has
gotten significantly stronger over time, which is
making it more difficult to develop new painkillers
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
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 relief5,6
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:
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.