From the point of view of fundamental physiologists this is one of the more depressing results of medical research that the human brain can be tricked by placebos. From a positive standpoint though, it appears to be an essential part of medicine’s fascination. However – physicians love placebos and that with good reason.
Placebo? Sure! Why not!
Just how intensive this love is shows the latest data from the US. Bioethicists at the National Institutes of Health in Bethesda have published the results of a survey with 1200 practicing internists and rheumatologists. 679 physicians responded, i. e. 57 percent of the addressed. And – wonders never cease – half of those reported that they prescribe placebos on a regular basis. Interestingly enough every fifth plies openly and tells his patients that they are getting a placebo. The majority though “sells” the placebos (veridical after all) as some kind of trial therapy the prescriber had made good experience with in previous tests. The spectrum of applied placebos was rather wide, from saline solutions, sugar- and vitamin pills to real medications, mostly low dosed analgesics of OTC nature. Two out of three physicians stated that they consider the targeted prescription of placebos as ethically not problematic.
Researchers find a placebo-gene
Almost simultaneously with this publication, basic researchers piped up in the Journal of Neuroscience. They claimed to have found a gene which at least could explain a variant of the placebo effect. The scientists, originally from the field of neuropsychiatry, have thus made their examinations with patients with social phobia. In a randomized controlled study 108 of those patients were either treated with a new medication which impairs in the serotonin metabolism of the brain or with a placebo. The effect of the therapy was examined amongst others by PET. Frequently the amygdala is hyperactive in patients with social phobia which can be displayed very nicely in colors. To get the patient in a phobia ridden situation the patients – at the beginning and at the end of study – had to hold a speech in front of a group of spectators while the PET recordings were made. In this case the psychologist Tomas Furmark and the scientists at Swedish University of Uppsala were only interested in the placebo group during the following analysis. Ten of 25 patients treated with placebo reported a reduction of their fear problems. And the PET scan displayed it as a decrease of amygdala activity.
Bye-bye Placebo studies?
So far – so typical. However the Swedish scientists took a look at the genes of the patients afterwards. They wanted to know whether there are any differences of the gene “responsible” for the serotonin metabolism in the brain between those test persons with a distinctive placebo effect and those without it. And indeed: Eight of the ten patients with a distinctive placebo effect had a specific variant of the tryptophan hydroxylase 2-promotor which is involved in the serotonin production. It is matter of a variant known also in healthy people standing out with a hyperactive amygdala during PET.
So there is a gene now which might be – at least partly – responsible for the placebo effect. This itself is quite interesting. But most of all it might lead to problems during placebo controlled clinical studies. “It at least might be tempting to screen all participants and select those with a non-responsive phenotype for the study”, speculates Furmark. The intention is clear: Those sorting out these patients expected to have a pronounced placebo effect will have a relatively high effectivity of the verum substance in the end compared to the control group. This has ethic but most of all statistic implications nobody really thought about intensively so far because the problem had not arisen. In the future this might or maybe even has to change…