Pricey Placebos

The placebo effect is a puzzling concept to get your head around. The idea that an essentially inert intervention — like a sugar pill, a saline injection, or a sham operation — can produce therapeutic benefit seems to defy common sense. But it’s very real. In Parkinson’s disease, the placebo effect has been found to be extremely strong (in some cases producing up to a 50% improvement of symptoms) and long lasting (in extreme cases persisting for as long as 18 months).

In their attempts to explain this fascinating phenomenon, placebo researchers have noted the importance of the “ritual of the therapeutic act”. Even without a pharmacologically active medicine, researchers argue, a patient attending a clinic or an operating room experiences a complex psychosocial process. She arrives at the medical center with expectations based on her knowledge, beliefs, and memories of past medical encounters. She sees doctors and nurses and observes, smells, and tastes medicines of different forms, colors, and shapes. She feels the touch of instruments like syringes. She hears the beeps and gurgles of medical machinery and listens to the words of those present.

This elaborate therapeutic ritual, they argue, is medically potent. For while the medicines may be fake, the processes going on in our brains are, of course, real, mediated by actual neurotransmitters. The brain, it seems, operates like a compounding pharmacy and synthesizes chemicals like opiates, dopamine, and more. It does so in response to “expectations”. Previous research has found that superficial qualities of placebos (such as a pill’s shape and color) affect those patient expectations and consequently the strength of the resulting placebo response. And now researchers have shown that the medical outcome of an intervention can be affected by the perceived price of the medicine as well.

Alberto Espay and colleagues report in Neurology how they told study participants with Parkinson’s disease that they were about to receive one of two different dopamine agonists — one priced at $100 per dose, the other costing a whopping $1,500 per dose. In fact, both formulations were not dopamine agonists but placebos — ordinary saline solution. According to the authors, those participants who believed they were taking the expensive drug experienced “a reduction in UPDRS-III score, by 28%” (indicating improved movement), whereas patients who thought they were getting the cheap drug improved by only half as much over baseline. As lead author, Dr. Alberto J. Espay remarks, this all comes down to the brain’s compounding pharmacy, as he puts it, “We make more dopamine when we have heightened expectations of efficacy.”

The placebo represents one of medicine’s enduring paradoxes — it’s a powerful healing effect that clinicians use daily and a troublesome confounder that complicates the search for therapies and cures. This study suggests that it might also be a factor driving health costs as well. Pharmaceutical companies seem to already know this. History shows that patients will frequently seek out newly packaged medications like Nexium (the purple pill) even though it is chemically essentially indistinguishable from a cheaper over-the counter formulation Prilosec.