Genetic 'placebo response' marker has trial design implications, say researchers
Scientists from Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School (HMS) claim to have identified genetic differences between people who respond to placebos during trials of and those who do not.
The team looked a 2003 trial (NCT00065403) in which patients ‘treated’ with augmented placebo – combined acupuncture and physician support – showed greater reductions in symptom severity than patients in either the limited placebo group – just acupuncture – or the no treatment arm.
Analysis of blood samples taken at the time showed patients who responded most strongly had two copies of a particular version of a gene encoding catechol-O-methyltransferase (COMT), an enzyme involved in the dopamine pathway, as lead author Kathryn Hall explained.
“IBS patients homozygous for the COMT val158met methionine allele were the most responsive to placebo treatment. Heterozygous patients showed an intermediate response, and homozygous valine patients showed essentially no placebo mediated symptom improvement.”
And while the researchers admit the study was only small scale – 262 adults took part and only 122 allowed blood samples to be taken – they suggest the genetic findings have wider implications for drug research.
“To our knowledge, this is the first study to demonstrate genetic modulation of true placebo effects disassociated from changes related to disease natural history and regression to the mean.
“Identifying biological characteristics of placebo responders and non-responders could be key to managing underlying placebogenic factors to benefit patients by delivering personalized medicine, for example by adjusting the dose of medication in accordance to the subject's placebo susceptibility or selecting a different class of drugs for the individualized patient.”
