The Incredible Power of Drug Cost on Treatment Response

Everyone is familiar with the placebo and nocebo effects – when the expectation of benefit or harm produces positive or negative effects, respectively.  Impressively, however, the power of such effects can be modulated on another level by incorporating cost into the placebo effect.

This fascinating little study tested the effect of two different placebo medications on motor and brain activation in patients suffering from Parkinson’s disease.  Initially, each patient received motor and fMRI testing before and after levodopa administration.  Then, on a subsequent visit, patients received subcutaneous injections of saline 4 hours apart – with participants being told each was the same novel dopamine antagonist, one of which was manufactured using a “cheap” manufacturing process and one using an “expensive” process.  Each participant again received motor and fMRI testing following each injection.

As somewhat expected, each placebo injection produced some improvement in motor function – with the effect reaching statistical significance and almost 30% improvement from baseline for the “expensive” placebo.  Even more impressive, the “expensive” placebo was not too far off the effects of levodopa, which produced approximately a 50% improvement in motor symptoms from baseline.  Most entertainingly, however, the placebo effects were even present on fMRI imaging.  The “expensive” placebo showed brain activation levels similar to levodopa, while the “cheap” placebo had a differing distribution of activity apparently consistent with increased effort.

Yet again, the very real power of placebo – with its magnitude of effect tied to expectations related to cost!

“Placebo effect of medication cost in Parkinson disease”
http://www.ncbi.nlm.nih.gov/pubmed/25632091

Inside a Neurologist’s Mind: tPA For Everyone!

We all have our anecdotal stories from academic medical centers staffed by stroke neurologists, cases in which they have called for thrombolytic therapy in acute ischemic stroke for profoundly inappropriate candidates.  Hearing such sad tales, one hopes such rogue uses of lytics are the lunatic fringe, isolated cases of madness and zealotry.

But, no.

This survey of general and vascular neurologists at two academic institutions in New York demonstrates such aggressive use of tPA for stroke is the pervasive norm, rather than an isolated occurrence.  These authors provided 40 clinicians with a survey consisting of 110 case scenarios of patients presenting with symptoms of acute stroke.  These case scenarios were further stratified by NIHSS, with 22 cases each of NIHSS 1 through 5.  Of the 17 clinicians responding, it was almost unanimous they would use tPA for all cases of NIHSS 3, 4, and 5.  Neurologists would use lytics 57% of the time at NIHSS 2, and 37% of the time with NIHSS 1.

Now, the NIHSS is non-linear, and significant disability can be present at NIHSS 1 and 2 – but even remotely considering lysis at NIHSS 1 or 2 should be the exception rather than an almost balanced split.  In a world where the new ACEP Clinical Policy draft is rolling back its level of recommendation for tPA, it is simply boggling to see how the other half thinks – that no frontier is too formidable for tPA.

“To Treat or Not to Treat?  Pilot Survey for Minor and Rapidly Improving Stroke”
http://www.ncbi.nlm.nih.gov/pubmed/25604250