Placebos aren’t just an important way to compare the statistical response of a group of patients placed on a drug, they can actually predict how individuals will respond to antidepressant medications with an active ingredient, a newly published paper in JAMA Psychiatry concludes.
Although we don’t really understand why, it is very well established that people given a pseudo-treatment (treatment lacking any effective mechanism) will often get better simply from having been told it should work. Consequently, trials of medications don't just need to show they're more effective than doing nothing, but that they also outperform placebo treatments.
Unsurprisingly some conditions are far more responsive to placebos than others. A large portion of the benefit from antidepressant drugs is also seen in people in drug trials given pills that look identical to the drug itself but contain only sugar.
A team at the University of Michigan has been exploring factors that make some people more likely to benefit from placebos than others, including finding genetic variations associated with increased placebo power. Their latest finding is that, when it comes to antidepressant medications at least, people who have a strong placebo response are particularly likely to benefit from actual medications.
This is not just a case of antidepressants building on a base effect, stronger in some people, produced by the placebo. Rather a strong placebo response served as a good indicator of an even stronger response to a real treatment.
The team investigated the responses of 35 medication-free patients with major depressive disorder (MMD) when given placebos for two weeks, followed by an antidepressant.
The greater the improvement participants described in their symptoms, the stronger the response of mu-opioid receptors (a set of protieins involved in reward and pain control) in brain regions known to be associated with depression. This was to be expected, both since mu-opioid release is known to alleviate depression and also because the mu-opioid system’s importance in placebo responses had been the subject of previous papers by the same team.
A PET scan shows the changes in mu-opioid response for people given a placebo (left)
is very similar to those given antidepressants (right). Credit: University of Michigan
More significantly, the team found a strong association between the mu-opioid response triggered by the placebo and the one seen subsequently from the real drug. Nearly half the response to antidepressant treatment could be predicted based on how well an individual reacted to the placebo.
"This is the first objective evidence that the brain's own opioid system is involved in response to both antidepressants and placebos, and that variation in this response is associated with variation in symptom relief," said first author Marta Pecina, in a statement.
The work could have applications in testing and design for drugs to treat depression, with Pecina noting that it, “Gives us a biomarker for treatment response in depression – an objective way to measure neurochemical compounds involved in response. We envision that by enhancing placebo effects, we might be able to develop faster-acting or better antidepressants."
People showing weak placebo responses might also be better suited to non-drug treatments.