Placebo

Published on 23/05/2015 by admin

Filed under Physical Medicine and Rehabilitation

Last modified 22/04/2025

Print this page

This article have been viewed 969 times

CHAPTER 18 Placebo

When used as a noun, placebo means a treatment that lacks any specific therapeutic effect. In the case of a drug, a placebo would be an agent that lacks any pharmacological effect. In the case of a procedure, a placebo would be one that lacks any specific anatomical or physiological effect. Nevertheless, in other respects a placebo has all of the features of an intervention that should work.

When used as an adjective, placebo occurs in two forms: the placebo effect, and the placebo response. Placebo effect is the presumed or perceived effect that a placebo has on an individual. Placebo response is what the individual reports after having been administered a placebo, and is ostensibly due to the placebo effect.

Essentially, a placebo is not supposed to work. Any effect or response that it evokes is, therefore, paradoxical. The resultant paradox is difficult to handle in clinical practice. Consequently, placebo is a commonly misunderstood concept that is subject to abuse, misinterpretation, and myths.

PLACEBO RESPONDER

When patients exhibit a placebo response, practitioners and authors sometimes, if not often, refer to them as ‘placebo-responders.’ This term implies that the patient has an inherent trait that means that they will consistently respond to placebos. This is wrong.

There is no personality trait or psychological trait that causes individuals to respond consistently to placebos.¹ Experimental studies have shown that any individual at any time is liable to express a placebo response, depending on the circumstances; but also that such responses are not consistent.¹^–³ Indeed, one authority has ventured to conclude that proneness to placebo is universal.⁴

The placebo response is a variable phenomenon, and does not reflect anything about the individual who reports it. The term placebo responder, therefore, can have only a pejorative connotation, to dismiss or relegate patients for having exhibited a paradoxical phenomenon. When used, it expresses more about the prejudices of the practitioner than anything about the patient. Consequently, the term should be expunged from clinical vocabulary, and never used.

PLACEBO RESPONSES ARE FAKE

Some practitioners handle the paradox of placebo responses by dismissing them on the grounds that the patient has a psychological problem, is malingering, or is frankly lying. This is both a misinterpretation and misrepresentation of the placebo response.

The distinction is that a placebo response occurs after the intervention, ostensibly because of it. In contrast, malingering and lying require premeditation. To accuse a patient of malingering or lying, because they have a placebo response, is therefore tantamount to accusing them of premeditation. The placebo response provides no evidence of this. Such an interpretation, therefore, reflects the prejudices of the practitioner.

Nor is the placebo response a sign of psychological distress. Placebo responses occur under experimental conditions in individuals with no evidence of psychological disturbance.^5,⁶ Among patients with chronic pain, profiles of psychological distress do not differ between patients who have true-positive responses to placebo-controlled diagnostic blocks and those who have placebo responses,⁷ or between patients who have successful outcomes after treatment and those who do not.⁸

NOT IN CLINICAL PRACTICE

A common belief, though rarely enunciated, is that placebo responses occur only in research studies and, reciprocally, that they do not occur in ‘real’ practice. Implicitly, placebo responses are somehow precipitated only if and when patients enroll in controlled trials.

This is a self-serving belief, designed to excuse practitioners in the ‘real’ world of any responsibility to be alert to placebo responses, or to have their practices accountable to placebo effects. The belief conveniently ignores the realization that controlled trials are simply the means by which placebo responses can be demonstrated and quantified. That having been done, practitioners are warned to expect the same phenomenon, with the same prevalence, in conventional practice. Practitioners choose to ignore this warning. They prefer, instead, to believe that all positive therapeutic effects of their practice must be due to the specific effects of their ministrations, and that their successes could not be due to something as ephemeral as a placebo effect. Under these conditions, ignoring the prevalence of placebo effects serves to protect the ego of a practitioner, while offending scientific accountability to the truth.

CONSTANT RATE

A widespread urban myth is that about one-third of patients in any cohort will express a placebo response, implying some sort of endemic influence. This myth has been traced to an early study of placebo responses.^1,³ In reviewing the literature, Beecher⁹ encountered a wide variety of placebo response rates, ranging from 15% to 58%. A figure of 35.2% arose as a numerical average of these rates, unweighted for sample sizes. Subsequent studies have encountered placebo response rates from as low as 0% to as high as 100%.¹ There is nothing constant about 35%. Placebo response rates differ considerably according to the circumstances of the study.

MECHANISM

In the context of pain medicine, a placebo would be an agent or a procedure that should have no effect on pain by pharmacological, anatomical, or conventional physiological means. A placebo response would be relief of pain despite this lack of a conventional means by which the pain could be relieved. The occurrence of a placebo response implies a placebo effect.

The mechanism or mechanisms of that placebo effect remain largely elusive. Theories have been proposed; but, of late, experimental studies have pursued its physiological basis.

The fact that pain is relieved implies that whatever the mechanism is of placebo effects, it must involve the nociceptive system. The prevailing theories about placebo invoke some sort of suppression at one level or another of the nociceptive system.

Conditioning

Conditioning is a prominent theory amongst psychologists who seek to explain the placebo effect.^2,³ The theory is based largely on data from experimental studies, in which subjects previously exposed to an intervention have continued to express positive responses when that intervention was surreptitiously or progressively replaced with a sham intervention.

However, it is hard to reconcile this theory with the nature of interventional spine medicine. If anything, patients are likely to encounter repeated failures of treatment and, therefore, would be conditioned not to respond. Indeed, the conditioning theory has been adapted to fit this phenomenon by becoming an explanation for nocebo responses or ‘placebo sag.’² In contrast, if the contention is that patients expect relief when they consult a doctor, instead of conditioning theory, expectation is a more appealing explanation.

Expectation

One of the prominent explanations for the placebo effect is that patients who undergo a treatment for pain expect the treatment to work.^2,³ This expectation can be reinforced if the practitioner engenders or fosters the expectation. It is reinforced if the treatment is undertaken in an impressive manner in an impressive setting, such as a high-tech facility. Indeed, factors found to enhance the placebo effect are: the credibility of the therapist, the credibility of the therapeutic setting, the credibility of the treatment, the credibility of the administrative setting, and the nature of the interaction between the patient and the therapist.²

The expectation model implies an interruption of the pain experience at a cortical level. One could say that the patient imagines receiving relief, because that is what is expected to occur. More graciously, one could infer that a subliminal, cortical effect occurs, in which the patient is distracted from the pain by the promise of expected relief.

Since they involve cerebral mechanisms, these conjectures are difficult to test. The pathways and processes are not amenable to experimental manipulation. Another interpretation, however, is that cerebral processes may invoke spinal mechanisms.

Spinal mechanisms

Diffuse noxious inhibitory control (DNIC) operates as a normal physiological process within the nociceptive system. Under normal conditions, its function is to discriminate incoming nociceptive information by center-surround inhibition. Under artificial conditions, however, DNIC can suppress nociception.

Suppression occurs when brainstem nuclei are stimulated globally, which sends inhibitory influences through descending pathways to all segmental levels of the spinal cord. This is one of the purported mechanisms of acupuncture, and the possible mechanism by which deep brain stimulation relieves pain. Conversely, systemic opioids work by globally inhibiting descending pathways. The resultant loss of inhibition causes any nociceptive information to be obscured by uninhibited background noise at the spinal level of the nociceptive system.

Placebos might work if subliminal cerebral processes activate the descending nociceptive systems. Under those conditions, placebo responses are not psychological in nature, but involve physiological processes in the central nervous system. Indeed, those processes are similar to or the same as those by which drugs and neuroaugmentative surgery achieve relief of pain. The distinction is only that the mind, rather than an exogenous agent, switches on the descending inhibition.

Circumstantial evidence to this effect arises in experiments in which placebo responses have been reversed by the administration of opioid antagonists such as naloxone.^1,^3,^5,¹⁰ Conversely, antagonists to cholecystokinin enhance placebo analgesia.⁶ The fact that drugs, known to block analgesic pathways in the brainstem and spinal cord, also block placebo effects implies that the same physiological systems are involved.

Meaning model

The meaning model invokes quite a different process.³ It suggests that, in order to maximize the placebo response, the patient must feel listened to, must receive what they perceive to be a valid explanation for their illness, feels care and compassion from their treatment environment, and feels empowered.

This model does not invoke antinociception, nor does it invite it. Instead, it predicts that patients who exhibit a placebo response are ones who have amplified their symptoms, at the time of treatment, because of fear, ignorance, and forlornness. When these are addressed, the amplification is removed; the report of pain is less; and the treatment appears to have relieved pain. Psychic amplification can be reduced by directly addressing the patients’ fears and ignorance, and having them feel understood and cared for. Alternatively, the same effects might occur circumstantially when a practitioner delivers an otherwise inactive treatment but with confidence and conviction, which implicitly relieves the patient’s psychic concerns.