David Baxter PhD
Late Founder
Power of Suggestion: When Drug Labels Make You Sick
By MELINDA BECK
November 18, 2008
Is it a good idea to read about all the possible side effects of medications you're taking?
Not if you have difficulty concentrating, headaches, fatigue, dry skin, irritability, a big project due, or an active imagination.
Research has shown that expecting to feel ill can bring illness on in some instances, particularly when stress is involved. The technical term is the "nocebo effect," and it's placebo's evil twin. "It's not a psychiatric disorder -- it's the way the mind works," says Arthur Barsky, director of Psychiatric Research at Brigham and Women's Hospital in Boston.
Nocebos can even be fatal. In one classic example, women in the multi-decade Framingham Heart study who thought they were at risk for heart attacks were 3.7 times as likely to die of coronary conditions as women who didn't have such fears -- regardless of whether they smoked or had other risk factors.
Research deliberately causing nocebos has been limited (after all, it's kind of cruel). But in one 1960s test, when hospital patients were given sugar water and told it would make them vomit, 80% of them did.
Studies have also shown that patients forewarned about possible side effects are more likely to encounter them. In a study last year at the University of Turin, Italy, men taking finesteride for enlarged prostates who were informed that it could cause erectile dysfunction and decreased libido were three times as likely to experience such side effects as men who weren't told.
"People's expectations play a very important role in how they react to all medications," says Richard Kradin, a physician and psychoanalyst at Massachusetts General Hospital in Boston, and author of "The Placebo Response and the Power of Unconscious Healing." He notes that about 25% of patients who get completely inert placebos in clinical trials complain of side effects -- typically headaches, drowsiness and dizziness.
For such vague complaints, one explanation may be that they are always present in the general population. In a 1968 study of healthy subjects not taking any medications, 39% reported fatigue, 14% reported headaches and 5% reported dizziness. Only 19% said they had no symptoms at all in the past three days.
Symptoms like rapid heart beat, dry mouth, nausea and diarrhea can be traced to the body's response to stress (say, from fearing illness.) Anxiety prompts the hypothalamus, pituitary and adrenal glands to release a cascade of hormones that make the heart pound and the stomach clench. Experiments have also shown that telling patients they may feel pain triggers the release of the neuropeptide cholecystokinin (CKK), which heightens pain sensations. When patients are given a drug that blocks CKK, the nocebo pain vanishes.
The rare, serious side effects listed on drug package inserts -- say, toxic epidermal necrolysis, in which one's skin falls off in large sheets -- are less subject to nocebo effects.
"All that information is really for the doctor, not the consumer," says James Barton Jr., a Birmingham, Ala., attorney who represents drug makers. Under the Learned Intermediary rule, once a company warns the prescribing doctor about a drug risk, responsibility in case it occurs shifts to that doctor. "There's an incentive to warn everybody about everything, but it fosters this climate of supervigilance and alarm," says Dr. Barsky.
If you are inclined toward health anxiety, reading up on your malady or medication on the Internet can fuel your fears. "Once you are anxious, there is all kinds of ambiguous information you can find that will make it worse," says Dr. Barsky.
Doctors may unwittingly foster placebo or nocebo effects by how enthusiastically or warily they discuss medication. "Physician communication with patients is the closest thing to magic. It gets communicated in incredibly subtle ways?a flash in the eye, a smile, a spring in the step," says Daniel Moerman, an emeritus professor of anthropology at the University of Michigan-Dearborn. Doctors may also subconsciously transmit an expectation of pain. In a double-blind study of 60 patients who had wisdom teeth extracted, when clinicians thought they might be administering a medication that could heighten the pain instead of lessen it, the patients reported much more pain?even though they were really receiving placebos.
Should doctors discuss all those risks with patients, or can they be a self-fulfilling prophecy? It depends on the patient and the drug. "Patients should be made aware of anything that could be dangerous, so they don't keel over on the street," says Flavia Golden, an internist in New York City. "But if it's minor like a headache, I don't mention it. It's better to keep the channels of communication open and say, 'Call me if you have any problems.' "
Some patients are more prone to worrying about side effects and researching them, in which case a discussion of nocebos might be helpful.
How should doctors treat a nocebo? With a placebo, naturally. "If it's relatively minor, you can treat it with reassurance or say 'Take two Tylenol and call me in the morning,' " says Dr. Kradin.
By MELINDA BECK
November 18, 2008
Is it a good idea to read about all the possible side effects of medications you're taking?
Not if you have difficulty concentrating, headaches, fatigue, dry skin, irritability, a big project due, or an active imagination.
Research has shown that expecting to feel ill can bring illness on in some instances, particularly when stress is involved. The technical term is the "nocebo effect," and it's placebo's evil twin. "It's not a psychiatric disorder -- it's the way the mind works," says Arthur Barsky, director of Psychiatric Research at Brigham and Women's Hospital in Boston.
Nocebos can even be fatal. In one classic example, women in the multi-decade Framingham Heart study who thought they were at risk for heart attacks were 3.7 times as likely to die of coronary conditions as women who didn't have such fears -- regardless of whether they smoked or had other risk factors.
Research deliberately causing nocebos has been limited (after all, it's kind of cruel). But in one 1960s test, when hospital patients were given sugar water and told it would make them vomit, 80% of them did.
Studies have also shown that patients forewarned about possible side effects are more likely to encounter them. In a study last year at the University of Turin, Italy, men taking finesteride for enlarged prostates who were informed that it could cause erectile dysfunction and decreased libido were three times as likely to experience such side effects as men who weren't told.
"People's expectations play a very important role in how they react to all medications," says Richard Kradin, a physician and psychoanalyst at Massachusetts General Hospital in Boston, and author of "The Placebo Response and the Power of Unconscious Healing." He notes that about 25% of patients who get completely inert placebos in clinical trials complain of side effects -- typically headaches, drowsiness and dizziness.
For such vague complaints, one explanation may be that they are always present in the general population. In a 1968 study of healthy subjects not taking any medications, 39% reported fatigue, 14% reported headaches and 5% reported dizziness. Only 19% said they had no symptoms at all in the past three days.
Symptoms like rapid heart beat, dry mouth, nausea and diarrhea can be traced to the body's response to stress (say, from fearing illness.) Anxiety prompts the hypothalamus, pituitary and adrenal glands to release a cascade of hormones that make the heart pound and the stomach clench. Experiments have also shown that telling patients they may feel pain triggers the release of the neuropeptide cholecystokinin (CKK), which heightens pain sensations. When patients are given a drug that blocks CKK, the nocebo pain vanishes.
The rare, serious side effects listed on drug package inserts -- say, toxic epidermal necrolysis, in which one's skin falls off in large sheets -- are less subject to nocebo effects.
"All that information is really for the doctor, not the consumer," says James Barton Jr., a Birmingham, Ala., attorney who represents drug makers. Under the Learned Intermediary rule, once a company warns the prescribing doctor about a drug risk, responsibility in case it occurs shifts to that doctor. "There's an incentive to warn everybody about everything, but it fosters this climate of supervigilance and alarm," says Dr. Barsky.
If you are inclined toward health anxiety, reading up on your malady or medication on the Internet can fuel your fears. "Once you are anxious, there is all kinds of ambiguous information you can find that will make it worse," says Dr. Barsky.
Doctors may unwittingly foster placebo or nocebo effects by how enthusiastically or warily they discuss medication. "Physician communication with patients is the closest thing to magic. It gets communicated in incredibly subtle ways?a flash in the eye, a smile, a spring in the step," says Daniel Moerman, an emeritus professor of anthropology at the University of Michigan-Dearborn. Doctors may also subconsciously transmit an expectation of pain. In a double-blind study of 60 patients who had wisdom teeth extracted, when clinicians thought they might be administering a medication that could heighten the pain instead of lessen it, the patients reported much more pain?even though they were really receiving placebos.
Should doctors discuss all those risks with patients, or can they be a self-fulfilling prophecy? It depends on the patient and the drug. "Patients should be made aware of anything that could be dangerous, so they don't keel over on the street," says Flavia Golden, an internist in New York City. "But if it's minor like a headache, I don't mention it. It's better to keep the channels of communication open and say, 'Call me if you have any problems.' "
Some patients are more prone to worrying about side effects and researching them, in which case a discussion of nocebos might be helpful.
How should doctors treat a nocebo? With a placebo, naturally. "If it's relatively minor, you can treat it with reassurance or say 'Take two Tylenol and call me in the morning,' " says Dr. Kradin.
