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* This is the Professional Version. *


By Shalini S. Lynch, PharmD, UCSF School of Pharmacy

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Patient Education

Placebos are inactive substances or interventions, most often used in controlled studies for comparison with potentially active drugs.

The term placebo (Latin for “I will please”) initially referred to an inactive, harmless substance given to patients to make them feel better by the power of suggestion. More recently, sham interventions (eg, mock electrical stimulation or simulated surgical procedures in clinical trials) have also been considered placebos. The term is sometimes used for an active drug that is given solely for its placebo effect on a disorder in which the drug is inactive (eg, an antibiotic for patients with viral illness).

Placebo effects

Placebos, although physiologically inactive, may have substantial effects—good and bad. These effects seem to be related to anticipation that the product will work; anticipation of adverse effects is sometimes called the nocebo effect. The placebo effect typically occurs with subjective responses (eg, pain, nausea) rather than objective ones (eg, rate of healing of leg ulcers, infection rate of burn wounds).

The magnitude of the response varies with many factors, including the

  • Expressed confidence of the clinician ("this is going to make you feel a lot better" vs "there is a chance this might help")

  • Certainty of the patient's beliefs (effect is larger when patients are sure they are receiving an active drug than when they know there is a chance they are getting a placebo)

  • Type of placebo (eg, injectable drugs have a larger placebo effect than oral ones)

Not everyone responds to placebos, and it is not possible to predict who will respond; correlations between personality characteristics and response to placebos have been theorized but not well established. However, people who have a dependent personality and who want to please their clinicians may be more likely to report beneficial effects; those with a histrionic personality may be more likely to report any effect, good or bad.

Use of placebos in clinical trials

Many clinical trials compare an active treatment with a placebo. The apparent effects of the placebo are then subtracted from the apparent effects of the active treatment to identify the true treatment effect; to be meaningful, a clinically and statistically significant difference is required. In some studies, the placebo relieves the disorder in a high percentage of patients, making it more difficult to show the active treatment’s efficacy.

Use of placebos in clinical practice

Rarely today, when a clinician determines that a patient has a mild, self-limited disorder for which an active drug does not exist or is not indicated (eg, for nonspecific malaise or tiredness), a placebo may be prescribed. The reasoning is that the placebo satisfies patients’ demands for treatment without exposing them to potential adverse effects and often makes them feel better—due to the placebo effect or spontaneous improvement.

Ethical considerations

In clinical studies, the ethical consideration is whether a placebo should be given at all. When effective treatment exists (eg, opioid analgesics for severe pain), it is typically considered unethical to deprive study participants of treatment by giving a placebo; in such cases, control groups are given an active treatment. Because participants acknowledge in advance that they may be given a placebo, there is no concern about deception.

However, when a placebo is given in medical practice, patients are not told they are receiving an inactive treatment. This deception is controversial. Some clinicians argue that it is prima facie (Latin for “at first view”) unethical and, if discovered, may damage the clinician-patient relationship. Others suggest that it is more unethical to not give something that may make patients feel better. Giving an active treatment solely for placebo effect may be further considered unethical because it exposes patients to actual adverse effects (as opposed to nocebo adverse effects).

* This is the Professional Version. *