You may have heard of the “placebo effect”, a thing that confounds medical experiments and confuses researchers.
But what if a placebo could in fact be a medicine on its own?
The word medicine comes from the Latin word “medeor”, meaning to cure diseases. A medicine is simply something that improves a person’s pain or disease. And the frontiers of understanding placebos may someday lead to their use as medicines as well.
Today, the most common application of a placebo is as false treatment. When drug companies want to verify the potential effect of a new drug, they carry out trials where the effects of the new drug are compared with those of a placebo. The placebo can be, for example, a pill that contains only sugar. Patients are told they could be taking medicine or placebo, but they don’t know which.
And often in these trials, there is a discernible “placebo effect.” The expectation of relief can cause the patient to experience some therapeutic improvement even if he or she is undergoing a dummy medical treatment.
Therefore placebos have a troubled standing within medicine. They seem to work, but do so rather unpredictably. And how precisely they exert their effects is still mysterious.
Speaking during a conference at the Royal Society of Medicine in London about the role of the placebo in clinical care, Dr Paul St. John Smith, a psychiatrist at Community Mental Health Team in Hertfordshire, said “People use [placebos] in different ways… We use it just as a psychological trick…to determine the real mechanistic instrumental effect of the drug or of an intervention… A lot of it is about what the patient perceives and not what has been given.”
And therein lies the crux of the placebo’s mystery. To what extent is the health of our body influenced by our mind? We live in a technology era, and yet we remain unaware of the functions of the most complicated machine that has ever existed – our brains.
Placebo vs antidepressants
One realm in which placebos have shown promise is in treating depression.
Professor Irving Kirsch, at the University of Hull in the UK, has analysed the placebo effect in clinical trials for antidepressants.
In a meta-analysis study published in 1998 (pdf), Prof Kirsch examined those clinical trials on antidepressants that had been published in the scientific literature. That analysis found that 75 per cent of drug activity could be attributed to the placebo effect. Moreover, patients who didn’t receive any kind of treatment experienced no significant improvement. This suggests that placebos are only slightly less functional than the actual medication, and much better than nothing.
In addition, placebos have none of the side effects of medications. Therefore, Prof Kirsch argues, “giving a placebo may be more ethical than giving other treatment both in clinical trials and clinical practice.”
After these findings, Prof Kirsch became curious whether unpublished studies confirmed this placebo effect. Pharmaceutical companies are not required to publish scientific papers on their clinical trials, and therefore often only positive results are reported in such papers.
Under the Freedom of Information Act, Prof Kirsch was able to obtain from the FDA (Food and Drug Administration) all the clinical trials’ data for the six most widely prescribed antidepressants approved between 1987 and 1999.
In 2002 Professor Kirsch published a meta-analysis study (pdf), revealing that 40 per cent of trials on antidepressants were unpublished, and of these studies only 12 per cent presented statistically significant benefits of drugs over placebo.
Viibrid (Vidalzone) is a popular antidepressant with an interesting story about its approval by the FDA. To be approved, antidepressants need to show benefits on the Hamilton Rating Scale, a scale used to evaluate the severity of the depression.
After five clinical trials that reported no significant benefits of Viibrid over placebo on the Hamilton Rating Scale, says Prof Kirsch, they found another scale, the Murders Scale, in which there still was not a significant difference between drug and placebo effect, but there was a chance that there might be, so other two massive trials were carried out. Finally the drug was approved by the FDA, though the failure of the previous five trials was not discussed.
In 2011 the FDA’s approval scale for antidepressants was permanently changed to the Murders Scale.
Placebo as painkiller
Depression is not the only condition for which placebos have been found effective. It has also been found in experiments addressing pain.
Pain is similar to depression in that it has a strong neural component. Numerous studies have demonstrated that there is a change in brain activity in patients undergoing placebo treatments. Anthony Jones, professor of neuro-rheumatology at Manchester University and leader of the Human Pain Research Group, referring to patients’ perception of pain, explains that “it’s a physiological phenomenon, not just people telling you what they want.”
The perception of pain has different components. When a person experiences pain that is unfamiliar, information flows from the part of the body stimulated to a specific area of the brain which elaborates the pain signals. However, when a person experiences pain that is familiar, also a different part of the brain is activated. That area retains a memory of chronic pains, and this memory has the effect of amplifying the pain feeling.
A recent experiment led by Fabrizio Benedetti (pdf), professor of clinical and applied physiology at the University of Turin Medical School, evaluated the pain relieving abilities of a placebo. A group of patients were given morphine for two days, and then placebo on the next day. Each of the five days they were asked to carry out a painful exercise: squeezing a hand-exerciser while a tourniquet was tight around their upper arm. The placebo showed significant pain relief over no drugs, given on days 1 and 5.
The same experiment was carried out by a second group of patients, except this time morphine was replaced by a non-opioid painkiller called Ketorolac. Again the placebo acted as the drug did.
A third experiment identical to the second one was carried out, but this time the fourth day patients were given placebo plus Rimonabant. Rimonabant is a drug that is supposed to block specific receptors activated by a placebo. This time the placebo displayed no effect. This suggests that, rather than the placebo effect being “all in the mind,” there is biological activity of a placebo in the brain that produces its effects.
Still, despite hundreds of trials that show the efficacy of placebos, they remain a laboratory tool rather than a formally approved clinical solution. But in a not too far future, perhaps the potential of placebos will be realised and they will be considered a real alternative treatment.