Scimex: The placebo effect, which makes you feel better just because you think
you're receiving treatment, is a well documented medical phenomenon but
the biological pathways involved have yet to be investigated. In a
review article, US scientists look at what is currently known about the
effect and discuss the possible ethical issues related to conducting
genetic tests to determine whether a patient is more prone to respond to
a placebo.
Researchers are beginning to explore whether the genetics of patients
who experience a placebo effect are different from those of patients
who don’t. It’s well known that people can feel better if they believe
they are receiving treatment, but the biological pathways involved are
relatively unexplored. In a new review, publishing April 13 in Trends in Molecular Medicine,
scientists at Beth Israel Deaconess Medical Center discuss what we know
as well as possible ethical issues related to conducting genetic tests
to determine whether a patient is a placebo responder.
“Understanding the placebome—the collection of genes related to
placebo responses—opens possibilities to improving patients’ responses
to clinical care and pharmaceuticals and to refining research designs
for detecting drug-placebo differences,” says lead author Kathryn Hall,
PhD, a member of Beth Israel Deaconess Medical Center’s Program in
Placebo Studies.
Past studies have revealed that certain signaling pathways in the
brain—especially the dopamine, opioid, endocannabinoid, and serotonin
pathways—help mediate the placebo effect. Hall and her colleagues
examined evidence that genetic variations in these pathways can modify
the placebo effect; their findings raise the possibility of using
genetic screens to identify placebo responders. Such information could
lead to better patient selection for clinical trials—for example by
pointing to those who should be excluded because they are likely to
experience a benefit no matter what treatment they receive or by
ensuring that potential placebo responders are evenly allocated across
treatment arms.
Hall notes that if the placebo response is influenced by certain
brain signaling pathways, then it might also affect patients’ responses
to drugs that target those same pathways, and the magnitude of the drug
effect might differ from one patient to another as a result of their
genotype.
“These are novel hypotheses that, to our knowledge, have not yet been
discussed in the scientific literature,” she says. “This broader
conception that points to more personalized medicine calls for
additional research.” Her group proposes including no-treatment controls
in addition to placebo controls in some future clinical trials. “Our
proposal to incorporate a formal placebo study into future clinical
trials is innovative and could represent significant cost savings,
leading to rapid access to knowledge of mechanisms involved in the
placebo response across a wide variety of disease and drug regimens,”
Hall says.
A number of ethical issues must be considered if genetic profiles of
placebo responders can be established. If high placebo responders are
not included in clinical trials, this raises several important
questions. For example, how will the drugs be labeled, and which
patients will be approved for treatment in light of the fact that the
drugs will have only been tested in placebo non-responders? Should
physicians test for genetic placebo-response propensities and should
patients be allowed to refuse permission to be tested? Should patients
be told about their propensity to respond to placebos, and could
patients refuse to know or refuse to have this designation in their
medical records? Would physicians be able to ethically use this
information and, if so, how? And of course, what if knowing one is a
placebo responder affects one’s placebo response?