The weird power of the placebo effect, explained
 

We've had numerous discussions about the placebo effect on this site over the past years. I thought this was an interesting new article and review of the effect.

The weird power of the placebo effect, explained - Vox

Thanks for posting this. I enjoyed having the opportunity to read it. I posted a link to it on the PsychCentral website as well. :Thanx:

Thanks Tupelo3 - there are some fascinating data there.

You hear many people on the Parkinson's forums say something like "I'm newly medicated with PD drugs, but don't feel any different. I still feel unwell". I've always thought that this was because the dose was too small to cross the "on"/"off" threshold, or because they did't have PD. However, a paper by Frisaldi [1] casts a different light on this. (Unfortunately, the paper is behind a pay-wall.) They report:

"We investigated the effects of prior exposure to apomorphine on the placebo response ... We found no placebo response if the placebo was given for the first time, whereas the placebo response was substantial after prior pharmacological conditioning with apomorphine ... These findings indicate that prior exposure to drugs is a critical factor in the occurrence and magnitude of placebo effects. These learning effects should be carefully assessed in clinical trials in which patients receive the active treatment first and then are randomized. Indeed, this sequence may generate high placebo responders."

Not only is this likely to affect the efficacy of a placebo, but it could also affect the efficacy of the drugs themselves (think: total efficacy = true efficacy + placebo effect).

If the need for prior drug conditioning turns out to be the case for all Parkinson's drugs, it explains much of the variability in the response to them.

Back to the PwP being medicated for the first time. He/she has probably been in decline for at least a couple of years before being diagnosed and, possibly even longer before being given a treatment. In that time, they may have "forgotten" what it's like to feel "normal", so they don't benefit from the placebo effect.

It also relates to the titration process. Slowly increasing the dose is likely to make it less likely to pick up the placebo effect. This is because expectations are likely to drop after one or more failed attempts to find an adequate dose.

Reference:

[1] "The placebo effect on bradykinesia in Parkinson's disease with and without prior drug conditioning."
Frisaldi E1, Carlino E1, Zibetti M1, Barbiani D1, Dematteis F1, Lanotte M1, Lopiano L1, Benedetti F
Mov Disord 2017
The placebo effect on bradykinesia in Parkinson's disease with and without prior drug conditioning. - PubMed - NCBI

John

COMT and RCT genes indicated
 

another angle :placebo may have physiological biomarkers ...

Genetics and the Placebo Effect: the Placebome

Thanks moondaughter; a very interesting paper.