Placebo: Difference between revisions
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Placebo treatment is not the same as no treatment. Normal treatment is the sum of natural history, placebo effect, and medical treatment. | Placebo means a treatment that lacks a specific therapeutic effect. For a drug it is an agent that lacks any pharmacological effect. For a procedure it is an intervention that lacks any specific anatomical or physiological effect. Placebo treatment is not the same as no treatment. Normal treatment is the sum of natural history, placebo effect, and medical treatment. | ||
== Definitions == | == Definitions == | ||
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# The non-specific effects are a paradox and are due to unknown mechanisms. The paradox is resolved if the unknown mechanisms of the nonspecific effects become known. | # The non-specific effects are a paradox and are due to unknown mechanisms. The paradox is resolved if the unknown mechanisms of the nonspecific effects become known. | ||
Any treatment effect that is not due to the specific, intended effects of a treatment is referred to as the '''placebo effect.''' The term '''placebo response''' is | Any treatment effect that is not due to the specific, intended effects of a treatment is referred to as the '''placebo effect.''' The term '''placebo response''' is what the individual reports after receiving a placebo, with the results being due to the placebo effect. | ||
The total effect of an intervention may be a combination of both its physiological known specific effects, and unknown non-specific placebo effect. An absolute placebo effect is when the intervention has no known therapeutic physiological effect or an intervention that is designed to simulate medical therapy but doesn't have a specific therapeutic effect. The opposite of a placebo effect is a '''nocebo effect,''' where harm occurs for non-specific unknown reasons. | The total effect of an intervention may be a combination of both its physiological known specific effects, and unknown non-specific placebo effect. An absolute placebo effect is when the intervention has no known therapeutic physiological effect or an intervention that is designed to simulate medical therapy but doesn't have a specific therapeutic effect. The opposite of a placebo effect is a '''nocebo effect,''' where harm occurs for non-specific unknown reasons. | ||
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'''Cointervention''': It is important to rule out the effects of co-intervention. For example the simple act of mechanically inserting a needle during inject may in itself produce analgesia. | '''Cointervention''': It is important to rule out the effects of co-intervention. For example the simple act of mechanically inserting a needle during inject may in itself produce analgesia. | ||
== | == Psychological Theories == | ||
There are four main theories regarding the mechanism of the placebo effect.<ref name=":0" /><ref name=":1">Brody H. The placebo response. Recent research and implications for family medicine. J Fam Pract. 2000 Jul;49(7):649-54. PMID: 10923577.</ref> | There are four main psychological theories regarding the mechanism of the placebo effect.<ref name=":0" /><ref name=":1">Brody H. The placebo response. Recent research and implications for family medicine. J Fam Pract. 2000 Jul;49(7):649-54. PMID: 10923577.</ref> | ||
'''Classic Conditioning:''' | '''Classic Conditioning:''' This theory views the placebo response as a conditioned response to features of the treatment setting such as the doctor's style of dress, equipment, medication. Relief occurs because of past experiences of having relief from going to the doctor. This mechanism is hard to apply to chronic pain. If anything, patients with chronic pain are likely to have had repeated failures, and so would be conditioned ''not'' to respond. Viewing it from this negative viewpoint can be an explanation for nocebo responses and "placebo sag.'<ref name=":0" /> | ||
'''Response Expectancy Theory''': | '''Response Expectancy Theory''': This views the placebo response as being due to an expectation from the patient that a treatment will relieve their pain. This effect is magnified and reinforced if the treatment is undertaken in an impressive manner, and impressive setting. The placebo effect has been found to be enhanced through credibility of the doctor, therapeutic setting, treatment, administrative setting; and the nature of the interaction between the patient and doctor.<ref name=":0" /> | ||
'''Meaning Model''': The patient | '''Meaning Model''': This model views that part the patients symptoms may be amplified due to fear. It looks at what factors are needed to address fear and thereby maximise the placebo response: | ||
# The patient must feel listened to and receive a valid coherent explanation for their illness | |||
# The patient must feel care and compassion from the doctor | |||
# The patient must feel empowered. | |||
By having these three factors, any fears are reduced and pain and function may improve simply as a result of that.<ref name=":1" /> Delivering a treatment with confidence and conviction can also also allay fear. | |||
'''Cognitive Dissonance Theory:''' The patient avoids holding two psychologically inconsistent beliefs: that the treatment would work and only very sick people don't improve. To reduce this dissonance the patient alters their perception of their symptoms. | '''Cognitive Dissonance Theory:''' The patient avoids holding two psychologically inconsistent beliefs: that the treatment would work and only very sick people don't improve. To reduce this dissonance the patient alters their perception of their symptoms. | ||
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== Response Rate == | == Response Rate == | ||
A commonly quoted figure is that 35% is the standard incidence of placebo response rates. However this figure, published in 1955, was the average placebo responses in 15 papers.<ref>BEECHER HK. The powerful placebo. J Am Med Assoc. 1955 Dec 24;159(17):1602-6. doi: 10.1001/jama.1955.02960340022006. PMID: 13271123.</ref> In fact, the incidence of placebo response varies between 0 and 100% depending on the disease, environment, investigator, and other factors. Furthermore, | A commonly quoted figure is that 35% is the standard incidence of placebo response rates, or otherwise stated as one third of patients will exhibit a placebo effect. However this figure, published in 1955, was the average placebo responses in 15 papers, with the range being 15-58%.<ref>BEECHER HK. The powerful placebo. J Am Med Assoc. 1955 Dec 24;159(17):1602-6. doi: 10.1001/jama.1955.02960340022006. PMID: 13271123.</ref> In fact, subsequent studies has found that the incidence of placebo response varies between 0 and 100% depending on the disease, environment, investigator, and other factors.<ref>Wall PD. The placebo effect: an unpopular topic. Pain. 1992 Oct;51(1):1-3. doi: 10.1016/0304-3959(92)90002-S. PMID: 1454391.</ref> The "constant" 35% figure is a myth. | ||
Furthermore, any given individual can be both a placebo responder and a placebo non-responder under different settings. There is no such thing as a personality or psychological trait that causes individuals to consistently respond to placebos.<ref name=":2">Voudouris NJ, Peck CL, Coleman G. Conditioned response models of placebo phenomena: further support. Pain. 1989 Jul;38(1):109-116. doi: 10.1016/0304-3959(89)90080-8. PMID: 2780058.</ref><ref name=":0">Peck C, Coleman G. Implications of placebo theory for clinical research and practice in pain management. Theor Med. 1991 Sep;12(3):247-70. doi: 10.1007/BF00489609. PMID: 1721730.</ref><ref name=":1" /> | |||
In patients with chronic spinal pain, there is no difference in the psychological profiles of patients who have true-positive responses to placebo-controlled diagnostic blocks and those who have placebo responses.<ref>Lord SM, Barnsley L, Wallis BJ, Bogduk N. Chronic cervical zygapophysial joint pain after whiplash. A placebo-controlled prevalence study. Spine (Phila Pa 1976). 1996 Aug 1;21(15):1737-44; discussion 1744-5. doi: 10.1097/00007632-199608010-00005. PMID: 8855458.</ref> There is also no difference between patients who have successful outcomes after successful treatment with radiofrequency neurotomy with those who do not.<ref>Wallis BJ, Lord SM, Bogduk N. Resolution of psychological distress of whiplash patients following treatment by radiofrequency neurotomy: a randomised, double-blind, placebo-controlled trial. Pain. 1997 Oct;73(1):15-22. doi: 10.1016/s0304-3959(97)00060-2. PMID: 9414052.</ref> | |||
== Magnitude == | |||
Essentially every pain intervention has a placebo component. In placebo controlled trials, the magnitude of the effect of placebo analgesics is typically ~50-80% of the active agent. For example with a baseline pain of 6, and active agent might reduce it to 3, while a placebo might reduce it to 4 or 5. | |||
== Clinical Application == | == Clinical Application == | ||
Revision as of 13:34, 13 September 2021
Placebo means a treatment that lacks a specific therapeutic effect. For a drug it is an agent that lacks any pharmacological effect. For a procedure it is an intervention that lacks any specific anatomical or physiological effect. Placebo treatment is not the same as no treatment. Normal treatment is the sum of natural history, placebo effect, and medical treatment.
Definitions
Adequately defining placebo is challenging. Any treatment or intervention can have both specific effects and non-specific effects.
- The specific effects are due to known physiological mechanisms.
- The non-specific effects are a paradox and are due to unknown mechanisms. The paradox is resolved if the unknown mechanisms of the nonspecific effects become known.
Any treatment effect that is not due to the specific, intended effects of a treatment is referred to as the placebo effect. The term placebo response is what the individual reports after receiving a placebo, with the results being due to the placebo effect.
The total effect of an intervention may be a combination of both its physiological known specific effects, and unknown non-specific placebo effect. An absolute placebo effect is when the intervention has no known therapeutic physiological effect or an intervention that is designed to simulate medical therapy but doesn't have a specific therapeutic effect. The opposite of a placebo effect is a nocebo effect, where harm occurs for non-specific unknown reasons.
Placebo analgesia is the reduction or disappearance of pain, through the placebo effect, when a placebo is given to a patient who is told that it is a painkiller.
Comparison with Other Effects
The placebo effect is a specific phenomenon that is sometimes confused with other effects.
Natural history: some conditions naturally improve over time because of healing or some other factor. The improvement in pain is a property of the disorder that the patient has not the placebo effect. These two effects are distinguished through comparing the outcomes of patients taking placebo and the outcomes of patients having no treatment ("no treatment group").
Regression to the mean: Patients with chronic pain may be more likely to present to a doctor and join a trial when their pain is on the more severe end of what they have been experiencing to date. Conversely, patients who are doing well compared to their average are less likely to present to doctors and enrol in trials. There is therefore an overrepresentation of patients who are in a severe period of their naturally fluctuating pain levels. Measurements of pain and function may not represent their normal state, but the state of their flare. Regression to the mean refers to the statistical phenomenon that on average their pain is likely to improve to their previous average level of pain, regardless of treatment. This is not a placebo effect, but simply reflects normal fluctuations in pain. This effect can be controlled through using appropriate selection criteria.
Hawthorne effect: When individuals are being observed there is a change in performance simply because they know they are being studied. This is a conscious or subconscious change.
Symptom Ambiguity and Biases: This can be controlled by using objective physiological measurements.
Cointervention: It is important to rule out the effects of co-intervention. For example the simple act of mechanically inserting a needle during inject may in itself produce analgesia.
Psychological Theories
There are four main psychological theories regarding the mechanism of the placebo effect.[1][2]
Classic Conditioning: This theory views the placebo response as a conditioned response to features of the treatment setting such as the doctor's style of dress, equipment, medication. Relief occurs because of past experiences of having relief from going to the doctor. This mechanism is hard to apply to chronic pain. If anything, patients with chronic pain are likely to have had repeated failures, and so would be conditioned not to respond. Viewing it from this negative viewpoint can be an explanation for nocebo responses and "placebo sag.'[1]
Response Expectancy Theory: This views the placebo response as being due to an expectation from the patient that a treatment will relieve their pain. This effect is magnified and reinforced if the treatment is undertaken in an impressive manner, and impressive setting. The placebo effect has been found to be enhanced through credibility of the doctor, therapeutic setting, treatment, administrative setting; and the nature of the interaction between the patient and doctor.[1]
Meaning Model: This model views that part the patients symptoms may be amplified due to fear. It looks at what factors are needed to address fear and thereby maximise the placebo response:
- The patient must feel listened to and receive a valid coherent explanation for their illness
- The patient must feel care and compassion from the doctor
- The patient must feel empowered.
By having these three factors, any fears are reduced and pain and function may improve simply as a result of that.[2] Delivering a treatment with confidence and conviction can also also allay fear.
Cognitive Dissonance Theory: The patient avoids holding two psychologically inconsistent beliefs: that the treatment would work and only very sick people don't improve. To reduce this dissonance the patient alters their perception of their symptoms.
Biochemical Mediators
The evidence is compelling that the placebo effect is due to biochemical effects, and is not a purely psychological phenomenon.
Endogenous opioids are involved. The placebo effect is reversed by naloxone. It is enhanced by antagonism of cholecystokinin receptors. Placebo analgesia can mimic the respiratory depression side effect seen with exogenous opioids, and this side effect is reversible with naloxone.[3]
There is also some evidence that catecholamines and cortisol are involved.
Response Rate
A commonly quoted figure is that 35% is the standard incidence of placebo response rates, or otherwise stated as one third of patients will exhibit a placebo effect. However this figure, published in 1955, was the average placebo responses in 15 papers, with the range being 15-58%.[4] In fact, subsequent studies has found that the incidence of placebo response varies between 0 and 100% depending on the disease, environment, investigator, and other factors.[5] The "constant" 35% figure is a myth.
Furthermore, any given individual can be both a placebo responder and a placebo non-responder under different settings. There is no such thing as a personality or psychological trait that causes individuals to consistently respond to placebos.[6][1][2]
In patients with chronic spinal pain, there is no difference in the psychological profiles of patients who have true-positive responses to placebo-controlled diagnostic blocks and those who have placebo responses.[7] There is also no difference between patients who have successful outcomes after successful treatment with radiofrequency neurotomy with those who do not.[8]
Magnitude
Essentially every pain intervention has a placebo component. In placebo controlled trials, the magnitude of the effect of placebo analgesics is typically ~50-80% of the active agent. For example with a baseline pain of 6, and active agent might reduce it to 3, while a placebo might reduce it to 4 or 5.
Clinical Application
The placebo effect can be enlisted in clinical practice simply through practice style and behaviour of the doctor in an ethical way.[2]
Sustained Partnership: Having a long term relationship with patients can lead to better outcomes. The ethical attitudes that enhance the placebo response rate are expressing interest in the total person, providing longitudinal care, being adaptive to the patient's idiosyncrasies, and avoiding cookbook medicine. From the patients side they must feel like they are in a caring, sensitive, and empathetic environment, and also view the doctor as reliable and trustworthy. Share decision making is important.
Mastery: The patient should feel empowered, and change from feeling like a passive entity that is totally dependent on the doctor, to feeling like they are in control of their health. They should be encouraged to express their ideas, concerns, and expectations.
Story: This is the narrative that is weaved by the doctor in a way that the patient can understand. Management is often easier when there is a cohesive and coherent narrative. Patients get less analgesic response if they are unaware that they are receiving an analgesic. They do better if they are expressly told that they are receiving a strong painkillers.[6] It is vital that patients understand how the analgesic works, what they are for, and how to use them properly.
Placebo should not be used as sole therapy. Otherwise it can delay seeking more effective treatments, it can reduce the future response of active therapy, it can add to treatment cost, it can result in a nocebo effect, and it can be a constant reminder of illness.
References
- ↑ 1.0 1.1 1.2 1.3 Peck C, Coleman G. Implications of placebo theory for clinical research and practice in pain management. Theor Med. 1991 Sep;12(3):247-70. doi: 10.1007/BF00489609. PMID: 1721730.
- ↑ 2.0 2.1 2.2 2.3 Brody H. The placebo response. Recent research and implications for family medicine. J Fam Pract. 2000 Jul;49(7):649-54. PMID: 10923577.
- ↑ Amanzio M, Pollo A, Maggi G, Benedetti F. Response variability to analgesics: a role for non-specific activation of endogenous opioids. Pain. 2001 Feb 15;90(3):205-215. doi: 10.1016/S0304-3959(00)00486-3. PMID: 11207392.
- ↑ BEECHER HK. The powerful placebo. J Am Med Assoc. 1955 Dec 24;159(17):1602-6. doi: 10.1001/jama.1955.02960340022006. PMID: 13271123.
- ↑ Wall PD. The placebo effect: an unpopular topic. Pain. 1992 Oct;51(1):1-3. doi: 10.1016/0304-3959(92)90002-S. PMID: 1454391.
- ↑ 6.0 6.1 Voudouris NJ, Peck CL, Coleman G. Conditioned response models of placebo phenomena: further support. Pain. 1989 Jul;38(1):109-116. doi: 10.1016/0304-3959(89)90080-8. PMID: 2780058.
- ↑ Lord SM, Barnsley L, Wallis BJ, Bogduk N. Chronic cervical zygapophysial joint pain after whiplash. A placebo-controlled prevalence study. Spine (Phila Pa 1976). 1996 Aug 1;21(15):1737-44; discussion 1744-5. doi: 10.1097/00007632-199608010-00005. PMID: 8855458.
- ↑ Wallis BJ, Lord SM, Bogduk N. Resolution of psychological distress of whiplash patients following treatment by radiofrequency neurotomy: a randomised, double-blind, placebo-controlled trial. Pain. 1997 Oct;73(1):15-22. doi: 10.1016/s0304-3959(97)00060-2. PMID: 9414052.
