Take This Sugar Pill and Call Me in the Morning

How is it that patients feel better even when they know they have been getting a placebo? Several studies shed light on the mind-body quandary.

Can a drug be therapeutic even if lacks any active substance? "Placebos without Deception," is the name of a research study conducted by experts at Harvard Medical School, headed by Prof. Ted Kaptchuk, in collaboration with researchers from Beth Israel Deaconess Medical Center (BIDMC ) of Boston. The study, published in December 2010 by the PLoS ONE online journal, examined the effect of placebo pills on sufferers of irritable bowel syndrome (IBS ), with a catch: the pill-takers were informed that the medicine contained nothing more than sugar.

Placebos are usually used as control variables in studies that examine the efficacy of a new medicine. As early as the 1950s researchers, such as Dr. Henry K. Beecher, recognized the placebo effect in which a patient's health is enhanced by the use of a dummy pill devoid of any medical agents. Beecher, who, in the absence of suitable medication gave his patients "bread pills," was amazed to discover that 30 percent of the pill-takers attested to a relief of symptoms. Since then the placebo effect has fascinated doctors, psychologists and other researchers. Every year studies are conducted to probe the biological parameters of the phenomenon and measure the scope of its effect.

pill - Ayala Tal - 13122011
Ayala Tal

The Harvard-BIDMC study group featured 80 patients, 70 percent of them women, aged 18-47. One group of patients received dummy pills, which were described as containing mainly sugar; the patients were told that studies show that these pills influence people through a self-healing process. The second group did not receive any medication. "We printed the word 'placebo' on the pills' packages and we told people in this [first] group that they don't have to believe in the impact of the placebo effect, but we insisted that they take the pills," says Prof. Kaptchuk. Even the researchers were surprised by the findings of the study in which 59 percent of placebo takers reported a reduction in IBS symptoms, compared to just 35 percent of those in the group who did not take pills.

'Red pills work better than colorless ones'

"People behave according to context and circumstances. This is true with regard to medical or pharmaceutical treatment," explains Dr. Ofer Caspi, Director of the Integrative Medicine Section at the Rabin Medical Center, Beilinson Hospital. "People respond to the name of the medicine, its color, size and cost. The way medicine is taken has a big impact. Having a shot is more effective than taking a pill. A red shot is more effective than a colorless one; and an operation is considered the most effective treatment. That is to say, we are accustomed to a hierarchy. Patients respond to suggestions. If a person is told that there is a medicine that 'really helps,' such a suggestion exerts real influence upon his situation."

Prof. Rafael Gorodischer of the Patient Safety and Risk Management Unit at the Soroka Medical Center in Be'er Sheva, believes that "the expectation of success in treatment and the patient's motivation are related to effects of placebos. Another factor is classical 'Pavlovian' conditioning, as a result of a learning process."

How can the improvement experienced by patients who knew they were taking sugar pills, devoid of medical agents, be explained? "There is a placebo effect in every area of medicine," explains Caspi. "The main condition upon which the effect is predicated is the patient's awareness. If I give a patient treatment while standing behind a curtain, and he does not know that he received treatment, he cannot accord any meaning to what's happened, and so he won't respond to it. If a patient is given something after an operation, without informing him about an anticipated effect of the pill, there will not be a placebo effect."

Caspi continues: "In evolutionary terms, the placebo effect is the body's internal pharmacy. The body knows how to excrete substances in response to suggestions. If it is a pain, the body will excrete anti-pain substances. If the body suffers from Parkinson's, it will excrete dopamine. Of course a woman won't become pregnant as a result of suggestions of holy intervention, but the rate at which women become pregnant increases in proportion to the contextual stimuli to which we respond."

Gorodischer says that there is scientific proof of biological processes occurring under the influence of dummy pills, and he notes that the placebo effect can be nullified.

Researchers from the Karolinska Institutet in Stockholm have studied the placebo effect via brain scans. After pain was induced in volunteers, and then eased by the infusion of opioids (pain-killing substances ) or by the injection of a placebo, the flow of blood to parts of the brain endowed with opioid receptors increased.

"Another proof of metabolic processes connected to the placebo effect was furnished by treatment of Parkinson's sufferers, as well as sufferers of depression and drug addiction," notes Gorodischer. "In some instances there is evidence that the taking of a placebo influences the immune system." Yet he warns that it is unwise to rely on placebos alone in treatment of diseases that have a clear psychological component.

Health in the eye of the beholder

In a study published last July in the New England Journal of Medicine asthma sufferers were divided into four groups: one was able to use an inhaler filled with Albuterol; another got a bronchodilator muscle relaxer; the third group received a placebo-filled inhaler along with treatment akin to acupuncture; and the fourth got no treatment and simply waited until the asthmatic symptoms vanished. Patients in the first three groups attested to symptom relief; but only treatment with the Albuterol inhaler actually led to changes in lung activity.

This study raised the question of whether medical treatment is effective when a patient reports a reduction of symptoms, or only when there is proof of an actual effect on the cause of the ailment. This question is at the heart of an article published by the American anthropologist Prof. Daniel Moerman in the same New England Journal of Medicine edition.

Moerman questions the disdain shown by researchers regarding reports made by patients about symptom relief in cases where there was no correlation between the subjective testimony of patients and the results of the lung examination. Is ignoring the testimony of patients the right line of interpretation, he wonders. Moerman points out that patients seek treatment not because they had scientific evidence of issues with their lung activity, but because they suffered from breathing problems. The question thus arises of what counts more: the doctor's view of the disease, or the patient's subjective perception of it?

Moerman believes that there is a long list of diseases that share a common denominator: They can be treated, in full or part, by the use of placebos. Do these studies and their results mean that treatment schedules ought to be altered, via (for example ) reducing quantities of active medical agents contained by pills? Dr. Caspi has his doubts about such an option.

He points to a need for "regulation of studies in which use is made of dummy pills in comparison to active [real] drugs. This method of research is a big mistake because it is based on simplistic thinking. In this comparative framework, the success of a treatment is explained entirely by the efficiency of a particular medicine, whereas poorer results of those in a control group who received dummy pills are attributed entirely to the placebo treatment. But a human being is a complex amalgam of mind and body, of psychology and physiology. Thus, when a patient in a study is given a high dose of a particular medicine (as compared to someone else who receives a dummy pill ), and the person then does not experience the same disease symptoms, say a migraine attack, that afflicts someone else, can you really be sure that the drug is what eliminated migraine symptoms? I believe that the dynamic here is more complex than that."