Nocebo/Placebo: Treatment Expectations and Preference in Chiropractic Care

A little more than a decade ago, the following opinion was shared by many of our stakeholders: "Academic medicine regards chiropractic theory as speculative at best and its claims of clinical success, at least outside of low back pain, as unsubstantiated ... yet, despite external conflicts and perhaps partly because of them, and despite the intraprofessional disagreements and uncertainty about its scope of practice, chiropractic has found an internal coherence that has allowed it to become an enduring presence ... this integrity has to do with the profession's belief in the importance of biomechanics; the centrality of manual therapy, especially for the spine; and a clinical dynamic that provides patients with explanations, meaning, and concrete experiences that promote a strong patient-physician bond, a sense of caring, and a restored sense of well-being."¹

Today, the intellectual environment toward chiropractic has changed little despite the many successes recorded by chiropractic clinical research and an expanded scope of practice. There are still too many misinformed opponents of the profession who challenge these successes as nothing more than a placebo effect or natural history. As patient advocates, we should be concerned that these persistent, unfounded and misguided attacks negatively influence patient responsiveness and thereby degrade treatment outcomes. In other words, can patient expectations about treatment diminish or enhance treatment outcomes?

Negative Expectations and Clinical Response: The Nocebo Effect

Coined by Walter Kennedy in 1961, nocebo is Latin for " I will harm" and is used to describe a poor clinical response that is solely due to a patient's negative expectation and not anything inherent in the intervention itself.² "The nocebo effect consists in delivering verbal suggestions of negative outcomes so that the subject expects clinical worsening."³ The influence of social modeling on the nocebo/placebo response also has implications for the wide variety of media experienced by the general population and by those who suffer from pain conditions.⁴ For example, in the Framingham Heart Study, women who believed they were vulnerable to heart disease were nearly four times as likely to die as women with similar risk factors who did not share the negative expectation.⁵

In the psychiatric literature, these issues are generally discussed under somatoform disorders, the so-called conversion disorder hysterical neuroses. Extraordinary anxiety may be induced in segments of the population by the social media, resulting in mass psychogenic disorder or epidemic hysteria.⁶ No one is immune from mass sociogenic illness because humans continually construct reality and the perceived danger needs only to be plausible in order to gain acceptance within a particular group and generate anxiety.⁷

According to Benedetti, et al., "A nocebo procedure is per se stressful and anxiogenic. It basically consists in delivering verbal suggestions of negative outcomes so that the subject expects clinical worsening...Recent experimental evidence indicates that negative verbal suggestions induce anticipatory anxiety about the impending pain increase, and this verbally-induced anxiety triggers the activation of cholecystokinin which, in turn, facilitates pain transmission...All these findings underscore the important role of cognition in the therapeutic outcome and suggest that nocebo and nocebo-related effects might represent a point of vulnerability both in the course of a disease and in the response to a therapy."⁸

According to Kaptchuk and others: "Biomedicine created the apparatus of the placebo-controlled randomized clinical trial so that highly variable human clinical conditions could be studied with the mathematical precision of the laboratory experiment. Such trials provide the evidence for claiming that biomedical therapies are scientific and actually provide more than the effects of participation in a healing ritual ... For biomedicine, the placebo effect demarcates legitimate from illegitimate healing."⁹

Positive Expectations and the Placebo Effect

Placebo ( "I will please") was originally considered to be nothing more than a patient's positive expectation bias for a beneficial result. The placebo effect pertains to how placebos work and the placebo response measures how patients respond to placebos.

Kaptchuk suggests: "Alternative medicine may be an especially successful placebo-generating health care system ... The overwhelming majority of medical conditions treated by unconventional medicine fall into the following categories: highly subjective symptoms lacking identifiable physiologic correlates, chronic conditions with a fluctuating course often influenced by selective attention, and affective disorders ... these conditions are precisely those that researchers believe are especially susceptible to inordinately strong placebo responses: back and chronic pain, fatigue, arthritis, insomnia, asthma, chronic digestive disorders, depression, and anxiety ... alternative medicine has the advantage of always having an intervention scenario ... an intervention presumably has a greater effect than no treatment ... Also, to demonstrate 'active' intervention, alternative medicine treatments have unique feedback loops that are likely to facilitate, if not heighten, substantial placebo responses. For example, chiropractic adjustment often triggers an audible 'pop' so that the patient can hear the subluxation being fixed."¹⁰

Data from Zubieta and Stohler "confirm that specific neural circuits and neurotransmitter systems respond to expectation of benefit during placebo administration, inducing measurable physiological changes." These include the rostral anterior cingulate, orbitofrontal and dorsolateral prefrontal cortex, anterior and posterior insula, nucleus accumbens, amygdala, thalamus, hypothalamus, and periaqueductal grey matter. Dopaminergic activation was observed in the ventral basal ganglia, including the nucleus accumbens. Regional dopaminergic and opioid activity were associated with the anticipated and subjectively perceived effectiveness of the placebo and reductions in continuous pain ratings.¹¹

High placebo responses were associated with greater dopaminergic and opioid activity in the nucleus accumbens. Nocebo responses were associated with a deactivation of dopaminergic and opioid release. Some of these regions overlap with those involved in pain and affective regulation but also motivated behavior and reward responses.^11-12

Emerging research in psychoneuroimmunology is studying possible links between allergies, psychogenic illnesses, natural recovery and achieving drug-like effects without using drugs.¹³

The Canadian Medical Association published a systematic review of the literature on expectations of recovery and found that positive patient expectations were associated with better health outcomes in 15 of the 16 studies reviewed.¹⁴

Myers, et al., studied patient expectations as predictors of outcome in patients with acute low back pain as well as whether allowing unassisted choice of therapy modified expectations. They found that higher expectations for recovery were associated with greater functional improvement. However, they did not use a shared decision-making model to help patients make choices that matched their preferences or allowed interaction with health care providers. This meant that patients may not have been well enough informed to make the right decision. On the 0-10 scale, the average ratings for probable helpfulness were: 6.1 (+/- 2.96 ) for chiropractic; 6.1 (+/- 2.52 for acupuncture; 7.2 (+/- 2.27 ) for massage therapy; and 6.9 (+/- 2.51 ) for physiotherapy.¹⁵

In every clinical encounter with patients, doctors of chiropractic should remember that their patient's positive or negative expectations have the potential to modulate and influence behaviour, which could influence treatment responsiveness. Discussing these expectations and concerns could mitigate most, if not all, of the negative consequences and thereby maximize the beneficial effects of the chiropractic experience. The nocebo/placebo response may be operating in all treatments by all health care providers. Utilizing pro-health and wellness messages may help to influence the effectiveness of treatments.

References

1. Kaptchuk TJ, Eisenberg DM. Chiropractic: origins, controversies, and contributions. Arch Intern Med, 1998;158:2215-24.
2. Kennedy WP. The nocebo reaction. Medical World, 1961 Sept.;95:203-5.
3. Colloca L, Sigaudo M, Benedetti F. The role of learning in nocebo and placebo effects. Pain, 2008 May;136(1-2):211-218.
4. Robinson ME, Price DD. Placebo analgesia: widening the scope of measured influences. Pain, 2009 July;144(1-2):5-6.
5. Voelker R. Nocebos contribute to a host of ills. JAMA, 1996 Feb 7;275(5):345,347.
6. Weir E. Mass sociogenic illness. CMAJ, 2005;172(1):36.
7. Bartholemew RS, Wessely S. Protean nature of mass sociogenic illness: from possessed nuns to chemical and biological terrorism fears. Br J Psychiatry, 2002;180:300-6.
8. Benedetti F, Lanotte M, Lopiano L, Colloca L. When words are painful: unravelling the mechanisms of the nocebo effect. Neuroscience, 2007 Jun 29;147(2):260-71.
9. Kaptchuk TJ, Shaw J, Kerr CD, Conboy LA, Kelley JM, Csordas TJ, Lembo AJ, Jacobson EE. "Maybe I made up the whole thing": placebos and patients' experiences in a randomized controlled trial. Cult Med Psychiatry, 2009;33:382-411.
10. Kaptchuk TJ. The placebo effect in alternative medicine: can the performance of a healing ritual have clinical significance? Ann Intern Med, 2002;136:817-25.
11. Zubieta JK, Stohler CS. Neurobiological mechanisms of placebo responses. Ann NY Acad Sci, 2009 Mar;1156:198-210.
12. Scott DJ, Stohler CS, Egnatuk CM, Wang H, Koeppe RA, Zubieta J-K. Placebo and nocebo effects are defined by opposite opioid and dopaminergic responses. Arch Gen Psychiatry, 2008;65(2):220-31.
13. Eccles R. The power of the placebo. Curr Allergy Asthma Rep, 2007 May;7(2):100-104.
14. Mondloch MV, Cole DC, Frank JW. Does how you do depend on how you think you'll do? A systematic review of the evidence for a relation between patient's recovery expectations and health outcomes. CMAJ, 2001;165(2):174-9.
15. Myers SS, Phillips RS, Davis RB, Cherkin DC, Legedza A, Kaptchuk TJ, Hrbek A, Buring JE, Post D, Connelly MT, Eisenberg DM. Patient expectations as predictors of outcome in patients with acute low back pain. J Gen Intern Med, 2007;23(2):148-53.