From 2002 to 2006, the number of drugs that were axed after Phase-II clinical trials (volunteer trials) increased by 20% because the drugs couldn’t beat the placebos they were compared against. More recently, in 2008, a new gene therapy for Parkinson’s disease failed against the placebo. Similarly, in March 2009, Eli Lilly withdrew a new drug for schizophrenia because the placebo effect was double that expected. Also in March 2009, Osiris Therapeutics’ new drug for Crohn’s disease was also withdrawn due to a high placebo effect.
What is going on?
There are a few forces that have generated the increase. The first is powerful advertising. Advertising plays on the mind; the very vehicle of the placebo effect. The Pharmaceutical Industry have hugely increased their advertising expenditure in the past 20 years. Many years ago, drug advertising was little more than a few posters on the walls of surgery waiting rooms. Now, big pharma have created powerful ads that are so effective that patients taking drugs in the west really expect something to happen when they take them.
Now the act of taking any drug in the west brings with it powerful memories as well as even more powerful unconscious associations generated by the advertising that ensure that taking a drug has an effect. But the downside, not for the patients but for the industry, is that the same applies when they take a placebo. Expectancy is a key element of the placebo effect. The same memories and associations are activated that ensure that taking a placebo heals too. Ironically for the drugs industry, as advertising gets better so too does the placebo effect.
The second reason is that there is a growing flux of drug testing now taking place in developing nations. In these trials, poor people who are often deprived of medical care are suddenly able to get the drugs they need. Many are desperate, and have extremely high hopes for the ‘fancy western drugs’ they receive as well as high-level belief in them. Their perception of rich nations is people enjoying state of the art drugs and healthcare into their very old ages.
But hope and belief are also key elements of the placebo effect. Thus, placebos in poor countries often do better than they would do in other countries. And since the global placebo statistics are made up from trials everywhere in the world, the statistics from the poorer nations lift the overall placebo rate up a few points. Thus, as more and more trials are carried out in poor countries, the higher the placebo effect will get. You could say, with the fancy advertising and trials in developing countries, that the pharmaceutical industry has, ironically, been responsible for elevating the placebo effect and making its own drugs harder to get on the market. With similar irony, it was my own interest in the placebo effect as a scientist in the pharmaceutical industry that propelled me into studying the power of the mind over the body.
Another reason for the increase is due to an increase in the use of drugs to treat ‘psychological disorders’. In the past 20 years, there has been an increase in the number of conditions being diagnosed as ‘psychological disorders’. Pharmaceutical companies have ploughed increasing millions of dollars into their research and development.
But many of these psychological disorders involve areas of the brain that are also involved with our beliefs, expectations, hopes, thoughts of rewards, and how we understand and relate to each other. And these are the same areas that are active during a placebo response. Thus the placebo effect is unexpectedly high for conditions like depression.
For example, a 2008 study of Prozac (fluoxetine), Effexor (venlafaxine), Serzone (nefazodone), and Seroxat (paroxetine) covering 35 clinical trials that involved 5,133 patients found that the placebo effect accounted for 81% of the effect of these drugs. Thus, as more people are diagnosed with psychological disorders and the number of drugs used to treat them increase, the ratio of drugs for psychological disorders compared with all other drugs increases. And since they have a high placebo effect, the overall placebo effect also increases.
It’s a similar story with cardiovascular diseases. As cardiovascular disease is the leading cause of death in the west, in large part due to western dietary and lifestyle habits, drugs to treat it dominate the drug market. But drugs for cardiovascular diseases can also have a high placebo effect, which many believe is due to the strong brain-heart link. So as our diets and lifestyles worsen and our hearts pay the price, the drugs used to treat us ensure that the placebo effect is kept high.
Doctors/physicians have a hand in the increase too. Many are now much more aware that the placebo effect is not just a nuisance, or all in the mind, as was once thought, but that it is a real pharmacological phenomenon that produces physiological change in the brain and body. Thus, many doctors treat patients with more empathy and assurance than before in the hope that that will aid their recovery. Empathy and assurance also activate the placebo effect. As doctors show more care and confidence, patients get better faster, even when they are taking inert medication.
Consider, for instance, the results of a British Medical Journal paper that reported on 200 patients who had either been given a positive or a negative consultation by their doctor. For approximately the same medical conditions, the doctors told the patients what was wrong with them and that they would get better in a few days. Accordingly, 64% of them did get better over the next 2 weeks. But for the other half, the doctors told the patients that they weren’t sure what was wrong with them but to come back if they haven’t got better. Only 39% of this group got better…..64% versus 39% and the only difference was in how the doctor acted. For the first group, there was presumably more empathy and confidence.
There is a last unexpected factor that also increases the placebo effect. It’s difficult to quantify the degree of influence it has, but it’s sure to be exerting an increasing force. It’s us! Or at least, it’s our increasing knowledge of the placebo effect and our growing faith in our own capacity to affect our bodies.
In the past few years, research into the placebo effect has delivered a powerful new message. It is that our thoughts, beliefs, our hopes and our expectations impact our brains and our bodies. MRI studies now show beyond doubt that this is true. Recent brain research shows release of dopamine in the brain when Parkinson’s patients are given placebos, for instance. Other studies show release of the brain’s own version of morphine when people are given placebos instead of painkillers. And MRI scans of patients given placebos instead of Prozac show activation in the same areas of the brain.
One of the leaders in the field of placebo research, Fabrizio Benedetti, a neuroscience professor at the University of Turin School of Medicine and member of the Placebo Study Group centered at Harvard, recently wrote:
“The placebo effect has evolved from being thought of as a nuisance in clinical pharmacological research to a biological phenomenon worthy of scientific investigation in its own right.”
This kind of research is filtering into the public domain through the mainstream press, which raises everyone’s belief in the power of the mind. Popular general-public-focused books that discuss the mind-body connection, like ‘How Your Mind Can Heal Your Body’, ‘It’s the Thought that Counts’, ‘The Biology of Belief’, and ‘Molecules of Emotion’, also add to this. So as our collective awareness that the mind affects the body increases, it’s sure to elevate the placebo effect even more. The good news in all this is that we are beginning to recognize that we are not exactly powerless. Our own attitudes and beliefs, our hopes and our expectations, all play a part in our own healing.
A general, healthy way of being, then, is to cultivate a more positive attitude towards all that life throws our way. It might just help us live longer, healthier lives, and when we do get sick it might just help us recover faster.
Copyright 2021 David R. Hamilton PhD.