Are placebos getting more effective over time? What does it mean?

imagesThe placebo is the fake treatment at the heart of every clinical trial. It’s the sugar pill, the sham operation, the baseline to which the real treatment must be compared. The whole placebo thing started on a World War II battlefield, when a physician named Henry Beecher witnessed something extraordinary. A wounded soldier was in great pain, but Beecher and his colleagues had run out of morphine. A nurse gave the soldier an injection of salt water, telling him it contained the painkiller–and the man responded as though it really did. When Beecher returned to civilian life, he pointed out that this phenomenon, which he called the placebo effect, could be causing big problems in studies of new drugs. A new drug might seem effective because patients treated with it appeared to improve; but in truth it might not be more effective than, say, a sugar pill. Patients’ expectations might be responsible for a large part of the benefits that everyone had been ascribing to drugs. And If we can get more or less the same effect from a sugar pill, it doesn’t make sense to mess around with a medication that is bound to come with its own set of problems. That’s why in today’s clinical trials, we compare new treatments to either placebos or whatever the standard of care is (previous trials having shown the latter is more effective than placebo).

Here’s something interesting, though. It turns out that placebo treatments appear to have been getting more effective over time, at least for some conditions. Take antidepressants, for example. From 1980 to 2005, the improvement effect reported in the placebo groups of clinical trials doubled. There is no evidence that the effectiveness of the placebo has increased for disorders such as epilepsy. So it’s not clear how general this trend of increasing effectiveness is. But why would the placebo effect be getting stronger for conditions like depression?

One possibility is conditioning/expectations on the part of the patient. Perhaps, based on past positive medical experiences, patients have come to associate contact with a medical professional with feeling better. In other words, because people believe that being involved in trials will improve their health, it does. Maybe current patients have higher expectations than past patients. But it’s also possible that the change hasn’t occurred in the patients. In that study of changes in the placebo effect over time in antidepressant trials, the researchers found that the response was only evident if you looked at expert ratings of depression. If you looked at patient self-reports, there was no increase in the effect of the placebo over time. So what does that mean? Possibly that observer ratings are not very reliable. Maybe over the years, physicians have been getting increasingly confident about their results, and this is reflected in their assessment of patients. The authors argued that it is unlikely that the placebo effect has actually doubled over the last two decades.

In the popular press, some writers have viewed the increasing effectiveness of placebo treatments as an impediment to getting new drugs approved. After all, the more effective a placebo treatment is, the more effective a new drug has to be to prove itself. The idea is that patients are missing out on potentially effective meds because the placebo is more effective than it ought to be. In truth, researchers have found that the more effective a placebo, the more effective the comparison drug tends to be. So drugs that aren’t more effective than placebo may just not be that effective over and above the expectation/conditioning effect. The placebo may just be a convenient scapegoat for unsuccessful trials.

Whatever the reasons for the increase in the placebo effect over time, it makes sense to harness placebo power. One group that has been able to figure out how to capitalize upon the placebo effect is the pharmaceutical industry. As has been pointed out, they understand how important it is to set up specific expectations within the minds of their consumers. They carefully manage advertisements, medication names, and the way that pills look in order to create the idea that a given medicine will have a certain result. And it seems to work!

How could a placebo be used effectively by the typical doctor, though? The big hurdle here is ethics. Most people feel it isn’t right for a doctor to give a patient a sugar pill and pass it off as a “real” treatment. Of course this makes sense. But it’s also true that a physician doling out a sugar pill could truthfully say, in many cases, that the treatment they are prescribing has been shown to significantly reduce pain for a given condition. For example, in one unique experiment, patients with irritable bowel syndrome were randomized to several groups. Some were put on a study waitlist (because just signing up for a trial can result in improvement), some were given a placebo by a curt medical practitioner, and some were given a placebo by a warm practitioner who expressed optimism about their condition.  Each of these assignments was associated with increasingly good responses. Roughly 30% of those who were on the waiting list reported adequate pain relief, about 40% of patients with the curt doctor said their pain was under control, and over 60% assigned to the warm doctor/placebo group felt their pain was manageable. The same trend was seen for quality of life. Obviously the ritual of seeking medical help and receiving compassionate care is an important part of getting better.

Even if the ethical problems can be overcome, however, logistical problems remain. In this day and age, most of us google the medications our doctors prescribe prior to filling them. How could a placebo fit into our system? What would the doctor say he was prescribing? What would your prescription say? Obviously your physician must be honest, and a placebo won’t work if you know it’s a placebo. The placebo works well in clinical trials, where secrecy is a design feature, but how would it translate into the real world?

As placebo treatments are increasingly considered worthy of study themselves, it will be interesting to see if and how medical treatment changes to accomodate what we’ve learned.

P.S. Thanks to Lotus Eater for pointing out that changes in the placebo effect over time have been documented!