Placebo

A placebo is any medication or treatment expected to have no physiological effect; the generally synonymous term sham treatment is sometimes used to describe a surgical or other procedure, more visible than a pill. According to the United States of America National Library of Medicine, a placebo is defined as a "dummy medication or treatment. Although placebos originally were medicinal preparations having no specific pharmacological activity against a targeted condition, the concept has been extended to include treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol."

The use of placebos has many ethical issues, and they are different in the research and general clinical contexts.

History

Until the late 18th century, ‘placebo’ was used in a religious, not a medical context: an early Latin translation of the Hebrew Bible, (Psalm 116, verse 9), was rendered as Placebo Domine ("I will please the Lord"). In the medieval Catholic Church, ‘placebo’ was a funereal rite - Vespers for the Dead - which employed that Psalm. In the 13th century, mourners who were paid to attend a funeral were said to “sing placebos” of false praise, and in the 14th century, Chaucer named his obsequious, flattering courtier 'Placebo' in the Canterbury Tales.

However, in the late 18th century, ‘placebo’ was, in a Medical Dictionary of the time, “a commonplace method or medicine”. The transition to a medical meaning can be traced to the writings of William Cullen (1710-1790), the leading British physician of the 18th century. Cullen used the term ‘placebo’ at least twice in lectures given in 1772. In one, he described giving a placebo treatment to a Mr Gilchrist, whom he regarded as "absolutely incurable". With no hope that any treatment could cure Mr Gilchrist, he prescribed a placebo treatment - to comfort or please his patient. He used what we would now call an ‘active placebo’, rather than a substance which he knew to be certainly inert.

" I prescribed therefore in pure placebo, but I make it a rule even in employing placebos to give what would have a tendency to be of use to the patient."

From this, it is clear that Cullen’s definition of placebo treatment related to the intention with which it was being prescribed. A ‘placebo’ treatment as one given to please, but without any curative intent. A later passage reveals Cullen’s thinking more clearly. He describes a patient for whom he prescribed mustard, whose "stimulant power" he thought might be "useful in paralytic affections":

"I own that I did not trust much to it, but I gave it because it is necessary to give a medicine, and as what I call a placebo."

Thus, for Cullen, a placebo treatment was defined more by the physician’s lack of curative intention than the make-up of the compound being prescribed; when prescribing a placebo, he chose low doses of active compounds that might tend to work against the disease.

Placebo versus placebo effect

Placebo is different from a placebo effect, which is defined as an "effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion" Thus the placebo effect can be a component of the effect of a treatment that has a true physiologic role; whereas a placebo has no intention of physiologic benefit.

The placebo effect is very common. In a randomized controlled trial of pregabalin for fibromyalgia the following occurred:

A randomized controlled trial of
pregabalin versus placebo
for fibromyalgia

study group	Patients reporting at least "much" improvement in their pain
pregabalin	43%
placebo	35%

Among the patients who received pregabalin, most of the benefit was due to placebo effect. The benefit due to the drug was 43% minus 35% or 8%. Thus if 100 patients receive pregabalin:

• 35 will improve due to placebo effect
• 8 will improve due to pregabalin (number needed to treat is 100/8 or 13)
• 57 will not improve

Clinical use

The effectiveness of a placebo various in different settings according to the Cochrane Collaboration. More recent studies confirm this. A randomized controlled trial found that placebo medications that the patient perceives as more expensive will have more placebo effect than placebos that are perceived as less expensive.

Many doctors report prescribing medications in part for the placebo effect.

While some clinicians and ethicists argue that it is unethical to deceive patients by giving them a placebo, others, within constraints, suggest:

1. placebo can be an effective treatment.
2. Its use does not always entail deception.
3. In select cases, use of the placebo may even be morally imperative

In one case study, a patient complained of pain even after receiving an apparently appropriate opioid analgesic. The attending clinicians then, in addition, administered an injected saline placebo, suggesting it could help relieve his pain, and it did. The suggestion was not untrue. Had it not relieved the patient's pain, than additional interventions would have been appropriate, or, at the least, a careful risk-benefit analysis of these additional therapies. Most pain medicine specialists agree that with proper precautions, there is no upper limit to the opioid dosage that may be necessary to relieve pain.

Had the patient asked for specific identity of the drug, the treating personnel would be ethically required to tell the truth. The patient would be free to refuse it, but, if the responsible physician believed that the injection might indeed help the patient psychologically, using the placebo would be ethical.

An ethically acceptable way to offer a placebo, according to Lichtenberg and colleagues, could be:

I would like to offer you a pill which I believe can help lessen your suffering. I do not know exactly how it works. I have other pills to offer whose mechanism is clearer, but I am not sure that they will work better for you, and they may also entail more serious side effects.

Some would argue this is deceptive, but others make the counterargument that placebo effects are real. They contend that the argument that this is unethical assumes "only through pharmacology or similarly respectable and rational procedures can the doctor aid the patient. This has never been true, and even in an age of evidence based medicine remains untrue."

Another case where placebo use might be justified would be where a patient demands a specific pharmacologic treatment that the clinician believes is inappropriate, in the presence of a self-limiting condition. In such a case, the physician might administer a placebo, reassuring the patient that he will recover, but that the treatment given is more appropriate.

In yet another case, the clinician prescribes an appropriate dose of a drug, such as a tricyclic antidepressant, the pharmacological effect of which is known to start only after several weeks of taking the medication. If the patient reported immediate relief, it can reasonably be assumed that the relief is due to the placebo effect. This does become an ethical challenge if the patient is relieved, but the drug, even at a low starting dosage, is not without risk.

Ethical considerations for guidelines that result from this work might include:

• The first intent of prescribing the placebo must be the well-being of the patient. The decision must not be made because the treatment economically benefits the prescriber.
• When a placebo is offered, it must be in the sincere intent of relieving suffering. It would be unethical for the physician to give it simply in the interest of suppressing demands to "do something."
• If placebo does not help, it must be immediately stopped, and alternative treatment given if one exists. Rather perversely, not to withdraw the placebo in such a situation may lead to what could be considered a reverse effect: the patient might distrust a true analgesic or sedative, and psychosomatically resist its effects. In such a case, not only would the substitute drug not help, but it would expose the patient to increased risk without benefit.
• Placebo can be used only when standard treatment is ineffective, the side effects of the usual treatment are unacceptable, or there is no accepted treatment. This can lead to the challenging question of whether a referral might be made to a CAM practitioner, of a type that the physician does not believe will have any effect on the actual disease. It is quite arguable, however, that if the physician, in this situation, believes that a CAM method may actually help, it is unethical not to refer to such a practitioner.
• The physician must answer direct questions about the identity and expected effects of the placebo.
• If the placebo helps, it must be continued in the absence of a more effective treatment. If the placebo effect is unexpected, as in the case of immediate response to the tricyclic antidepressant, it cannot simply be stopped. Should the potential dangers of such a pharmacologic intervention be significant, then the physician must consider a safer alternative, even a true placebo, rather than discontinuing all treatment.

Adverse effects

Placebos may be associated with adverse effects.

Clinical choice of complementary and alternative medicine

One of the challenges in evaluating complementary and alternative medicine (CAM) is ruling out the placebo effect. If the conventional practitioner does not have a treatment to offer, and a CAM method, in the practitioner's experience, may help even if believed to be a placebo effect, it should be presented to the patient. In like manner, if the patient suggests a CAM approach that the physician believes would be ineffective or dangerous, the physician should make that opinion known, and then allow the patient to make his or her own choice.

If the patient has comorbid conditions for which conventional treatment is desired, as long as the CAM treatment will not interfere with the conventional treatment, the physician is not relieved from the duty of care for the other diseases. Should the physician be unwilling to continue to treat a patient that uses a CAM technique, that does not free the physician from the requirement to ensure continuing conventional care for other conditions. If the CAM treatment may directly interfere with other treatment, consultation with the CAM practitioner(s), bioethics resources, and possibly legal counsel becomes appropriate.

Research use

In any medical study, every patient—including those of a control group, if any—should be assured of the best proven diagnostic and therapeutic method. From The Declaration of Helsinki

The more common use of placebos is for the patients in the control group of a randomized controlled trial. The World Medical Organization's interpretation of the Declaration of Helsinki, says placebo controls are unethical if there is a standard treatment for the disease being studied. When no treatment is available, placebo controls are ethical. This is by no means agreed by all medical scientists.

It is a difficult issue in testing some complementary and alternative medicines in producing a suitable placebo for control. For some interventions, such as pharmaceutical drugs (or alternatives: homeopathy etc.), it is very easy to substitute a placebo pill. In other interventions, it is not necessarily as easy to do so and sometimes ingenious methods have to be used. In testing acupuncture, for instance, a number approaches are taken to placebo acupuncture: firstly, inserting acupuncture needles but not in accordance with traditional acupuncture theories of medians and chi - that is, inserting acupuncture needles randomly. Secondly, a fake, retracting acupuncture needle has been used, similar in design to a stage dagger. Other similar fake interventions have been tried for a variety of alternative and complementary treatment interventions, but have often been rejected by advocates of such treatments.