Placebo Effect Becoming More Powerful

The placebo effect is growing stronger in US clinical trials for chronic pain medications.

Recent failures of novel neuropathic pain analgesics in clinical trials have led health investigators to speculate the underlying reasons.

One of the more commonly considered possibilities is that placebo response in these trials has increased in recent years, blurring the line between treatment and placebo arms.

To test this theory, researchers analyzed the results of 84 clinical trials for neuropathic pain medications conducted between 1990 and 2013.

In 1996, the trial drug relieved symptoms in 27% more participants than placebo. But in 2013, a similar trial revealed that the drug candidate relieved symptoms in only 9% more participants than placebo.

However, this phenomenon was only seen in trials conducted entirely in the United States.

The study authors posited that a few things particular to US trials are at play, such as changes in trial length and size. They noted that “over the period analyzed, neuropathic pain [trials] have become bigger, longer, and conducted at more sites in the U.S.A., but not elsewhere in the world.”

“The positive relationship between trial duration and the magnitude of the placebo response might be explained by a positive feedback mechanism by which initially perceived pain reduction leads to increasing analgesia over the course of the trial,” the researchers posited.

Longer trials may also offer “more opportunities for—and ultimately richer—social support, attention from trial staff, and education.”

Bigger, better-advertised drug trials may also enhance the placebo effect by creating expectations among trial participants that the intervention will be more effective.

In a separate study published in PLOS Medicine in March 2008, researchers investigated the theory that direct-to-consumer (DTC) marketing may enhance the placebo effect by creating heightened expectations for how a drug works based on the information provided in ads.

They noted that DTC marketing is only legal in 2 industrialized countries worldwide: the United States and New Zealand.

Whatever the reason, when clinical investigators are unable to prove and establish a candidate drug’s superiority over placebo, then the treatment typically faces a longer, more difficult road to the market, if it ever makes it at all.

This research was published online in the Journal of the International Association for the Study of Pain in August 2015.