Gettysburg Medical News
The Clinical View
by P.E. Hoffsten, M.D.
20 February 2002

PLACEBO OR NOCEBO

     Medication side effects continue to be a major concern .  Not to diminish the seriousness of some drug side effects, the problem of  assigning a side effect or symptom to a drug is made much more complicated by something called the placebo effect or nocebo effect.

       The Latin derivation of placebo means “I will please”.  The classical example of a placebo effect can be shown in the person who has a tension headache.  If a drug is going to be used to treat headaches, the FDA requires that the drug be shown to be more effective than a placebo.  A placebo pill is one that is inert and has no predictable effect upon the body.  These are  commonly called “sugar pills”.  And yet it is a well known phenonoma that if a large group of people with headaches are given “a sugar pill”, 50% of them report that their headache is improved.  If a new drug is being tested for it’s effect on headaches, the FDA (Food & Drug Administration) requires that the drug be shown to be more effective than a placebo.  Either Aspirin or Tylenol improve headache symptoms in approximately 65-70% of the people who try the drug.  Products such as Darvocet or Talacen effectively reduce headache symptoms in approximately 80-85% of patients that use those medications.  Narcotics are over 90% effective in alleviating headache symptoms.

       Healthcare professionals rarely, if ever, prescribe a placebo.  It is disrespectful to the patient and their symptom and creates a clear and definite attitude problem for the healthcare professional in their relationship with the patient.  If a patient finds that they have been given a placebo unbeknown to them, the professional relationship is usually broken or badly tarnished. And yet the placebo effect is clear and definite.  Every new drug study that comes out has to make a comparison of the new drug’s effect against the effect of a placebo in the same group of patients.  In these situations, informed consent from the patient is first obtained letting them know that they may receive an active drug or they may receive a placebo in the study that is being carried out.  In a good study, the pills look exactly the same and the patient is unable to tell the difference.  As a general rule,  placebos create beneficial effects in 25% of the people that use them.  The headache example above is unusual in the very large placebo effect for that particular symptom.

      What about the opposite problem?  What about the situation where a person takes an inert pill and then develops negative symptom?   This is called the nocebo effect.  The Latin derivation of nocebo means “I will harm”.  As opposed to placebo effects which are positive, nocebo effects are negative but they derive from the same psychological phenomena except the patient perceives a negative or unpleasant symptom in response to the inert pill.

       The complexity of this problem can be illustrated by a study in which a large number of individuals taking no medications and having no known medical illness, were questioned about symptoms that they might have had in the previous three days.  Thirty-nine percent of these individuals questioned reported that they were fatigued.  Twenty-six percent reported difficulty concentrating.  Twenty-three percent reported drowsiness.  Fourteen percent reported that they had had headaches and five percent reported that they were dizzy.  The amazing number was that only 19% of all the individuals questioned had no symptoms at all in the previous three days and yet none of them were taking any medications, none of them were seeking medical attention and none of them had any reported medical illness.  The point being, symptoms are very common and not necessarily indicative of disease or a side effect from a drug.

       Certain situations will tend to accentuate the likelihood of a nocebo or a placebo effect. First and most important are the patient’s expectations.  If a patient has a suspicious mind set believing that drugs cause side effects, as soon as the medication is started, the person will begin to scan for symptoms that the drug might be causing.  Since 80% of people who take no medications and have no illness have some symptoms, it usually is no trick to find some symptom that can then be faulted to the drug.  The drug may be playing no part in the symptom the person has but if the person believes the drug is at fault ,to them that is a solid fact of life. The rules for the healthcare professional is to avoid “pushing” a medication to a patient who is suspicious or doesn’t want to use it.  There may be genuine and real benefit from using the medication but it is not going to work unless the patient is a willing participant in their care and wants to use the medication.

      Perhaps the worst law perpetrated upon the medical community is the requirement that our pharmacists provide a list of side effects that medications have.  Pharmacists are required to warn patients that whatever drug they might be taking has various side effects which will be listed in great detail on a handout that comes with the medication.  Even if the patient had no expectation that the medication might have a side effect, after reading the handout put out by the pharmacist, people can become clinically ill just reading about what might happen.  After reading some of these lists that the pharmacists pass out, I’m amazed that the patients ever take any medications.  The nocebo phenomenon is massively accented by this long list of symptoms that pharmacists issue with medications.

       The purpose of this column is to make individuals aware that there is definitely a placebo effect from medications.  But in addition, there is the mirror image of this which is called the nocebo phenomenon, people believing that a medication is causing a negative symptom even though there is no physiologic or pathologic basis to explain this.  Healthcare professionals prescribe medications with great care and the intent to provide benefits in treating or preventing disease.  True medical mistakes, unexpected side effects, and predictable side effects still occur. It is the healthcare professional’s obligation to make patients aware of predictable, adverse effects that a medication may have.  But the present system of issuing patients a long list of symptoms reported in people taking that medication contributes to the nocebo phenomenon and the lose of substantial medical benefit when a medication is necessary to prevent or treat disease. The healthcare professionals at your local clinic are well aware and well versed in regard to this problem and work with patients to allay unfounded fears or effectively deal with legitimate side effects medications might have.