Placebo Effect Puzzle Has Scientists Scratching Their Heads

Before a new drug comes to market, it must be proven to be more effective than a placebo. But what happens when a placebo becomes effective in treating most patients? 

Well, it becomes pretty darn challenging to prove a new drug's efficacy. 

We're already seeing the impact of placebo effect's explosion in America, at least when it comes to pain medication. As it's become more difficult to prove a new drug's advantage over the sugar pill, more than 90 percent of new drugs for neuropathic and cancer pain have not made it past the advanced phases of clinical trials. 

New research from McGill University, published last week in the journal Pain, has added another riddle to the placebo effect mystery. A comprehensive review of clinical trials for pain medications conducted in the U.S. and other countries shows that the placebo effect has gotten considerably stronger in the past 25 years -- but only in America. 

Researchers analyzed data from 84 drug trials for pain medication conducted between 1990 and 2013. The drugs were designed to treat neuropathic pain, a type of pain that stems from the nervous system. 

"We analyzed the data in a way that nobody had analyzed it before, and found this interaction with geography," Dr. Jeffrey Mogil, a pain researcher at McGill University and the study's lead author, told The Huffington Post in an email. "It was pretty stunning, and it was mostly stunning just by how robust the finding was." 

The analysis revealed that in U.S. trials conducted in 1993, pain medications were rated to be an average of 27 percent more effective than placebo pills. In the 2013 trials, however, the pain medication was only 9 percent more effective than the placebo. The difference wasn't attributed to decreased effectiveness of the medication, but instead to a greater response to the placebo. In other words, the sugar pill has become nearly as effective as medication in alleviating pain. 

Puzzlingly, the researchers did not observe this effect in other countries. Placebo effect remained largely the same over the course of the 23-year study period in trials conducted in Europe and Asia. 

While the growing power of placebo in the U.S. has been widely observed in recent years -- particularly in trials for painkillers and anti-depressants -- the new study is the first to show a major geographic difference in placebo effect.

Though the researchers don't have a clear explanation for why this might be happening, they do have a theory. One possibility is that people have developed higher expectations of a drug's effect because of the increasing fanfare around pharmaceutical trials -- they've become longer, larger and more costly -- which in turn, leads to an experience of reduced pain with the placebo.

"I think it's really a matter of how big and how long the trials are, rather than some difference between the people in the countries," Mogil said. "But again, it's all complete speculation."

If the placebo effect continues on its current trajectory, American pharmaceutical companies may find it increasingly difficult to get consumers to buy new drugs. 

It may be time to reexamine the way we've long conducted drug trials, according to Mogil.