Study Redefines Placebo Effect as Part of Effective Treatment
It's not Drug or Placebo; It's Drug and Placebo
ROCHESTER, N.Y., Dec. 22 /PRNewswire-USNewswire/ -- Researchers
used the placebo effect to successfully treat psoriasis patients
with one quarter to one half of their usual dose of a widely used
steroid medication, according to an early study published online
today in the journal Psychosomatic Medicine. Early results in human
patients suggest that the new technique could improve treatment for
several chronic diseases that involve mental state or the immune
system, including asthma, multiple sclerosis and chronic
pain.
By designing treatment regimens that mix active drug and
placebo, researchers at the University of Rochester Medical Center
hope to maximize drug benefits, reduce side effects, increase the
number of patients who take their medicine and extend the use of
drugs otherwise limited by addiction risk or toxicity. Using a
fraction of the usual drug dose to get the same effect could also
make possible a dramatic and timely reduction in healthcare costs,
according to the authors.
The publication is a product of decades of research in the
emerging field of "psychoneuro-immunology," which holds that the
ability of the human immune system to fight disease is closely
linked with a person's mind. Thoughts and moods are captured in
neurochemicals that cause the release of hormones which interact
with disease-fighting cells.
The current research team chose psoriasis for their first human
experiments because it is chronic, gets worse when patients feel
stress and involves the immune system. The condition causes pain
and disability in four million Americans as inherited traits and
irritants cause the immune system to trigger the too fast
production of skin cells, resulting in red, scaly patches of dead
skin.
"Our study provides evidence that the placebo effect can make
possible the treatment of psoriasis with an amount of drug that
should be too small to work," said Robert Ader, Ph.D., M.D. (hc),
distinguished university professor in the University of Rochester
School of Medicine & Dentistry. "While these results are
preliminary, we believe the medical establishment needs to
recognize the mind's reaction to medication as a powerful part of
many drug effects, and start taking advantage of it," said Ader,
professor of Psychiatry and principal investigator of the study.
The placebo effect, obviously, cannot help unconscious patients, or
replace substances that the body itself is unable to produce, he
added. In the absence of functioning islet cells, for example,
placebos cannot stimulate the release of insulin in a Type l
diabetic.
Study Details
A description of the current findings requires expanding the
definition of placebo effects to include phenomena that are not
fully understood by modern medicine, Ader said. Although placebos,
"dummy pills" that have no therapeutic effect by themselves, are
prescribed by many physicians today, their use still carries a
stigma. It's as if the effect of a pill containing no medication is
not "real," part magic and part deception.
To accurately define and study the placebo effect, Ader and
colleagues chose to frame it as an example of a well-established
psychological phenomenon: the conditioned response. Nineteenth
century Russian physiologist Ivan Pavlov was the first to study the
phenomenon of conditioning. By ringing a bell (a conditioned
stimulus) each day before giving his dogs food (an unconditioned
stimulus), Pavlov found that the dogs would eventually salivate (a
conditioned response) at the sound of the bell alone.
In the current study, Ader and colleagues sought to determine if
a drug's therapeutic effect could be triggered by qualities
associated with the drug, like its shape, color, smell and
packaging, as well as by its administration by an authority figure
in a white lab coat. These repeated associations, Ader argues,
create conditioned responses, drug-like therapeutic effects of
treatment caused, not by a drug's ingredients alone, but elicited
by stimuli associated with the effects of active drug treatment.
The results provide the first evidence that conditioned responses
might be harnessed to influence the design of drug regimens in
humans.
Research teams at the University of Rochester Medical Center and
Stanford University conducted an 11 to 14-week, double-blind,
randomized clinical trial in 46 patients with mild-to-moderate
psoriasis. Patients were on no other medications during the study,
and had signed consent forms after being informed they might
receive a reduced dose of topical steroid.
At the start of the study, researchers randomly selected two
"target" psoriatic lesions or sores on each patient. Twice each day
during a three-week baseline period, all patients spread a lotion
containing a full dose of steroid medication (0.1% Aristocort A,
triamcinolone acetonide) onto one of their two study lesions. The
second lesion was coated with a moisturizing cream. Medicated and
unmedicated creams were distributed in coded syringes to make them
indistinguishable.
Nearly all past drug studies divided patients into two groups
only. One would get the full dose of the drug all of the time (a
100 percent reinforcement schedule). The other would get zero drug
all of the time (zero percent reinforcement). The current study
asks for the first time: what if we treat patients with something
in between drug and placebo? After the three-week baseline period,
patients were randomly assigned to one of three groups.
The first continued to receive 100 percent of the treatment drug
at each administration for the rest of the study on his or her
study lesion. A second, the partial reinforcement group, also
continued to receive a full dose, but only 25 or 50 percent of the
time, and a steroid-free emollient the rest of the time. The study
was designed so that this second group could benefit from exposure
to cues they had previously associated with active drug treatment
(a conditioned therapeutic effect). A third group, the "dose
control group," received active drug at every administration, but
at 25 or 50 percent of the full dose used in the first and second
groups. Thus, the partial reinforcement and "dose control" groups
received the same total amount of active medication, but in
different patterns.
Results were measured in two ways. First, a "blinded"
dermatologist measured the severity of a patient's psoriasis
lesions weekly using the Psoriasis Severity Scale (PSS), a standard
tool used to track the redness, hardening and thickening of skin.
The second measure was whether a patient experienced a "relapse" in
lesion severity, defined arbitrarily as a return to a PSS score
within two units of a patient's initial score.
In terms of the overall PSS severity scores, results were mixed.
The Stanford study site found no group differences in PSS scores
that could be attributed to the different treatment regimens. Ader
believes that elevated baseline PSS scores in the randomly selected
Dose Control subjects at Stanford might have obscured the
differences between the dose control and partial reinforcement
groups. For instance, results could have been influenced by
differences in the amount of sun patients were exposed to in
Upstate New York and California (ultraviolet light is an
established treatment for psoriasis).
In Rochester, there were no differences between the PSS values
of the Partial Reinforcement and Dose Control groups at the point
in the study where experimental treatment began. In this case,
partial reinforcement brought about a greater reduction in lesion
severity during the experimental period than continuous
reinforcement (dose control) with the same cumulative amount of
drug.
The relapse results were clearer. Four of 18 patients (22.2
percent) in the 100 percent reinforcement group (full dose all the
time) relapsed within the eight-week experimental period. Among
patients treated with a full dose of drug, but one half or one
quarter of the time (50 or 25 percent reinforcement schedule), four
of 15 patients (26.7 percent) relapsed. Thus, the incidence of
relapse did not differ substantially between patients receiving a
full dose of drug all the time and those treated under the partial
reinforcement schedules, researchers said. In contrast, eight of
the 13 patients (61.5 percent) in the dose control group who
received active drug each time, but not the full does, relapsed in
the same period of time.
Thus, the incidence of relapse in the partial reinforcement
group (26.7 percent) was significantly less than in dose control
patients (61.5 percent) that received the same cumulative amount of
drug. Further studies are underway, and others are planned, to
confirm the effect, answer the questions raised and explore the
effect in other autoimmune diseases.
The study was conducted jointly by the Departments of Psychiatry
and Dermatology within the School of Medicine & Dentistry at
the University of Rochester and the Stanford University School of
Medicine. Along with Ader, the study was authored in Rochester by
Mary Gail Mercurio, James Walton and Deborra James. Leading the
effort at Stanford were David Fiorentino, Alexa Kimball, Michael
Davis and Valerie Ojha. The study was funded by a grant from the
National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIAMS), part of the National Institutes of Health
(NIH).
"The pharmaceutical industry may choose to ignore the
conditioning component of drug treatment regimens," Ader said.
"Alternatively, they may now consider exploring ways to exploit
conditioning in the design of drug treatment protocols, especially
in chronic conditions where patients acquire conditioned responses
over time. I believe industry will eventually support this approach
because it promises to increase safety and reduce production
costs."
Source: University of Rochester Medical Center
CONTACT: Greg Williams of the University of Rochester Medical
Center,
+1-585-273-1757
Web Site: http://www.urmc..rochester.edu/
Posted: December 2009
