The Role of Patient–Practitioner Relationships in Placebo and Nocebo Phenomena

doi:10.1016/bs.irn.2018.07.033

International Review of Neurobiology

Volume 139, 2018, Pages 211-231

https://doi.org/10.1016/bs.irn.2018.07.033 Get rights and content

Abstract

Introduction: Placebo and nocebo effects form part of all therapeutic environments and play a significant role in the effectiveness of treatment outcomes. Patient expectancies drive these phenomena, which can be shaped through contextual factors including verbal suggestions, conditioning, and social observation.

Objectives: This review seeks to identify the biopsychosocial factors of the patient–practitioner interaction that play a role in the development of placebo and nocebo effects, as well as the anthropological elements of the biodynamic process of relating that are meaningful in the development of expectancies.

Methods: We conducted a narrative review of frameworks of the placebo and nocebo effect, including the impact of expectancies and interpersonal relationships in the context of healing and the clinical setting.

Results: Expectancies leading to placebo and nocebo effects can be modified by macro and micro factors, such as culture and society, as well as individual psychobiological traits, respectively. The developmental sociobiological adaptations that form and consolidate mindsets and meaningful contexts play an important role in shaping patient expectancies, as well as patients' conscious and subconscious reactions to signs and actions taking place within the clinical environment. Practitioner characteristics, like empathy, friendliness, and competence, favor the formation of positive expectancies. Caring and warm patient–practitioner interactions can enhance the therapeutic value of clinical encounters when patients' positive expectancies are actively encouraged and engaged.

Conclusion: A patient-centered approach rooted in demonstrating care and empathy can positively enhance a patient's experience within the clinical environment and activate psychosociobiological adaptations associated with the placebo phenomenon. Pain patients could particularly benefit from non-invasive approaches for improving treatment effectiveness and quality-of-life.

Section snippets

Background

The placebo and nocebo effects have fascinated scholars for decades due to the powerful and significant impact they have on different experimental and health outcomes. Numerous and rigorous research has found that placebo and nocebo effects are associated to multiple eliciting factors, such as verbal suggestions, social observation, conditioning and prior experience, individual personality traits, and genetic variants (Blasini, Corsi, Klinger, & Colloca, 2017; Colagiuri, Schenk, Kessler,

The Patient–Practitioner Interaction: A Sociobiological Approach

The interaction between a patient and a healthcare provider has the potential to influence clinical outcomes through the continual psychosocial process of relating (Adler, 2007). Relating represents a set of complex interactions in which the engaged parties reciprocally effect the behavior, as well as the experience, of the other (Adler, 2007). Given that no psychosocial influence occurs without a precedent and subsequent psychophysiological response, this continual process may also

Interpersonal Healing

Research has suggested that physician expectations and beliefs influence their patients' clinical outcomes. A study by Gracely, Dubner, Deeter, and Wolskee (1985) compared postoperative pain after dental surgery in a double-blind setting. Patients were told that they would be administered fentanyl (opioid), naloxone (opioid antagonist), or a placebo. A total of 60 patients were divided into a placebo–naloxone (PN) group and a placebo–naloxone–fentanyl group (PNF). Doctors were told that

Signs and Meaning

As demonstrated by the open-hidden paradigm, interactions and communications serve as a vehicle for facilitating both placebo and nocebo effects. Miller and Colloca applied the theory of signs developed by American philosopher Charles Sanders Peirce, named semiotics, as a way to bridge the neurobiological, psychological and cultural components of the placebo effect with the concept of meaning (Colloca et al., 2011; Miller & Colloca, 2010). Peirce developed the theory of signs to form a

Connecting the Dots: A Clinical Approach

During a period of illness, patients often find themselves in a vulnerable and stressful position. In this case, the simple behavior of going to see a healthcare practitioner creates a context of healing that forms part of the therapeutic process (Adler, 2002). The physician himself/herself becomes a sign that conveys a meaning, whether positive or negative, depending on the context upon which prior and current interactions occur. Establishing a positive therapeutic alliance with patients is

Conclusion

Medicine is a field that has been inherently built through rituals and symbols such as the act of going to a doctor or healer, writing prescriptions, and administering medication (Kaptchuk, 2011). As part of a larger contextual process of relating, the placebo effect can be implemented to help enhance treatments. Empathy, positive interpersonal relationships, cultural competence and sensitivity, and personalized interactions according to identified meaningful mindsets and conceptions, can

Acknowledgments

This research was supported by the University of Maryland, Baltimore (L.C.) and the National Institute of Dental and Craniofacial Research (NIDCR, R01DE025946, L.C.).

References (82)

F. Benedetti et al.
Blockade of nocebo hyperalgesia by the cholecystokinin antagonist proglumide
Pain
(1997)
F. Benedetti et al.
When words are painful: Unraveling the mechanisms of the nocebo effect
Neuroscience
(2007)
B. Colagiuri et al.
The placebo effect: From concepts to genes
Neuroscience
(2015)
L. Colloca et al.
Overt versus covert treatment for pain, anxiety, and Parkinson's disease
The Lancet. Neurology
(2004)
L. Colloca et al.
Vasopressin boosts placebo analgesic effects in women: A randomized trial
Biological Psychiatry
(2016)
B.D. Darnall et al.
Optimizing placebo and minimizing nocebo to reduce pain, catastrophizing, and opioid use: A review of the science and an evidence-informed clinical toolkit
V. Faria et al.
Imaging the placebo response: A neurofunctional review
European Neuropsychopharmacology
(2008)
B.L. Fife
The role of constructed meaning in adaptation to the onset of life-threatening illness
Social Science & Medicine
(2005)
R. Gracely et al.
Clinicians' expectations influence placebo analgesia
The Lancet
(1985)
T.J. Kaptchuk et al.
Placebo controls, exorcisms, and the devil
The Lancet (London, England)
(2009)

A. Keller et al.

Placebo analgesia in rodents: Current and future research

International Review of Neurobiology

(2018)

I. Kirsch

Response expectancy theory and application: A decennial review

Applied and Preventive Psychology

(1997)

G.L. Petersen et al.

The magnitude of nocebo effects in pain: A meta-analysis

Pain

(2014)

D.D. Price et al.

Placebo analgesia is accompanied by large reductions in pain-related brain activity in irritable bowel syndrome patients

Pain

(2007)

S.G. Shamay-Tsoory et al.

The neural correlates of understanding the other's distress: A positron emission tomography investigation of accurate empathy

NeuroImage

(2005)

T.D. Shanafelt et al.

Changes in burnout and satisfaction with work-life balance in physicians and the general US working population between 2011 and 2014

Mayo Clinic Proceedings

(2015)

R. Sussex

Describing placebo phenomena in medicine: A linguistic approach

L.J. Young et al.

Neuroendocrine bases of monogamy

Trends in Neurosciences

(1998)

B.E. Wampold

The therapeutic value of the relationship for placebo effects and other healing practices

R. Ader et al.

Conditioned pharmacotherapeutic effects: A preliminary study

Psychosomatic Medicine

(2010)

H.M. Adler

The sociophysiology of caring in the doctor-patient relationship

Journal of General Internal Medicine

(2002)

H.M. Adler

Toward a biopsychosocial understanding of the patient-physician relationship: An emerging dialogue

Journal of General Internal Medicine

(2007)

H.M. Adler et al.

The doctor-patient relationship revisited. An analysis of the placebo effect

Annals of Internal Medicine

(1973)

S. Ballou et al.

Open-label versus double-blind placebo treatment in irritable bowel syndrome: Study protocol for a randomized controlled trial

Trials

(2017)

H.K. Beecher

The powerful placebo

Journal of the American Medical Association

(1955)

F. Benedetti

Placebo effects: Understanding the mechanisms in health and disease

(2009)

F. Benedetti et al.

The biochemical and neuroendocrine bases of the hyperalgesic nocebo effect

Journal of Neuroscience

(2006)

F. Benedetti et al.

Opioid-mediated placebo responses boost pain endurance and physical performance: Is it doping in sport competitions?

Journal of Neuroscience

(2007)

U. Bingel et al.

The effect of treatment expectation on drug efficacy: Imaging the analgesic benefit of the opioid remifentanil

Science Translational Medicine

(2011)

M. Blasini et al.

Nocebo and pain: An overview of the psychoneurobiological mechanisms

Pain Reports

(2017)

A. Branthwaite et al.

Analgesic effects of branding in treatment of headaches

British Medical Journal (Clinical Research Ed.)

(1981)

H. Brody

Placebo response, sustained partnership, and emotional resilience in practice

The Journal of the American Board of Family Practice

(1997)

C.S. Carter

Neuroendocrine perspectives on social attachment and love

Psychoneuroendocrinology

(1998)

C. Carvalho et al.

Open-label placebo treatment in chronic low back pain: A randomized controlled trial

Pain

(2016)

L. Colloca

Placebo, nocebo, and learning mechanisms

(2014)

L. Colloca

Tell me the truth and i will not be harmed: Informed consents and nocebo effects

The American Journal of Bioethics: AJOB

(2017)

L. Colloca et al.

Placebos and painkillers: Is mind as real as matter?

Nature Reviews. Neuroscience

(2005)

L. Colloca et al.

Nocebo hyperalgesia: How anxiety is turned into pain

Current Opinion in Anaesthesiology

(2007)

L. Colloca et al.

Experimental designs and brain mapping approaches for studying the placebo analgesic effect

(2008)

L. Colloca et al.

Relieving pain using dose-extending placebos

Pain

(2016)

L. Colloca et al.

Understanding placebo and nocebo responses for pain management

Current Pain and Headache Reports

(2014)

Cited by (61)

Updating beliefs about pain following advice: Trustworthiness of social advice predicts pain expectations and experience
2024, Cognition
Prior expectations influence pain experience. These expectations, in turn, rely on prior pain experience, but they may also be socially influenced. Yet, most research has focused on self rather than social expectations about pain, and hardly any studies examined their combined effects on pain. Here, we adopted a Bayesian learning perspective to investigate how explicitly communicated social expectations (‘advice about pain tolerance’) affect own pain expectations, and ultimately pain tolerance, under varying conditions of social epistemic uncertainty (trustworthiness of the advice). N = 72 female participants took part in a coldpressor (cold water) task before (self-learning baseline) and after (socially-influenced learning) receiving advice about their likely pain tolerance from a confederate, the trustworthiness of whom was experimentally manipulated. We used path analysis to test the hypothesis that social advice from a highly trustworthy confederate would influence participants' expectations about pain more than advice from a less trustworthy source, and that the degree of this social influence would in turn predict pain tolerance. We further used a simplified, Bayesian learning, computational approach for explicit belief updating to examine the role of latent parameters of precision optimisation in how participants subsequently changed their future pain expectations (prospective posterior beliefs) based on the combined effect of the confederate's advice on their own pain expectations, and their own task experience. Results confirmed that participants adjusted their pain expectations towards the confederate's advice more in the high- vs. low-trustworthiness condition, and this advice taking predicted their pain tolerance. Furthermore, the confederate's trustworthiness influenced how participants weighted the confederate's advice in relation to their own expectations and task experience in forming prospective posterior beliefs. When participants received advice from a less trustworthy confederate, their own sensory experience was weighted more highly than their socially-influenced prior expectations. Thus, explicit social advice appears to impact pain by influencing one's own pain expectations, but low social trustworthiness leads to these expectations becoming more malleable to novel, sensory learning.
Efficacy of Home-Based Transcranial Direct Current Stimulation Over the Primary Motor Cortex and Dorsolateral Prefrontal Cortex in the Disability Due to Pain in Fibromyalgia: A Factorial Sham-Randomized Clinical Study
2024, Journal of Pain
This randomized, double-blind, controlled clinical trial compared the effectiveness of home-based-(HB) active transcranial direct current stimulation (a-tDCS) over the left dorsolateral prefrontal cortex (l-DLPFC) or primary motor cortex (M1) with their respective sham-(s)-tDCS to determine whether a-tDCS would be more effective than s-tDCS in reducing pain and improving disability due to pain. The study included 102 patients with fibromyalgia aged 30 to 65 years old randomly assigned to 1 of 4 tDCS groups using a ratio of 2:1:2:1. The groups included l-DLPFC (a-tDCS, n = 34) and (s-tDCS, n = 17), or tDCS on the M1 (a-tDCS, n = 34) or (s-tDCS, n = 17). Patients self-administered 20 sessions of tDCS, with 2 mA for 20 minutes each day under remote supervision after in-person training. The Mixed Model for Repeated Measurements revealed that a-tDCS on DLPFC significantly reduced pain scores by 36.53% compared to 25.79% in s-tDCS. From baseline to the fourth week of treatment, a-tDCS on M1 reduced pain scores by 45.89% compared to 22.92% over s-tDCS. A generalized linear model showed a significant improvement in the disability scale in the groups that received a-tDCS compared to s-tDCS over M1 20.54% versus 2.49% (χ² = 11.06, df = 1, P < .001]), while on DLPFC the improvement was 14.29% and 5.77%, with a borderline significance (χ² = 3.19, df = 1, P = .06]), respectively. A higher reduction in serum brain-derived neurotrophic factor from baseline to treatment end was positively correlated with decreased pain scores regardless of the treatment group. The application of a-tDCS over M1 increased the heat pain threshold and the function of the descending pain inhibitory system.
These findings provide important insights: (1) HB-tDCS has effectively reduced pain scores and improved disability due to fibromyalgia. (2) The study provides evidence that HB-a-tDCS is a viable and effective therapeutic approach. (3) HB-a-tDCS over M1 improved the function of the descending pain inhibitory system and increased the heat pain threshold. Finally, our findings also emphasize that brain-derived neurotrophic factor, as an index of neuroplasticity, may serve as a valuable marker associated with changes in clinical pain measures.
Number NCT03843203.
Enhancing patient experience assessment with psychological care in severe mental disorders: A study of the PREMIUM program
2023, Asian Journal of Psychiatry
Incorporating the experiences of patients with severe mental disorders (SMD) into clinical practice offers valuable insights for optimizing psychological care's effectiveness with more patient-centered and personalized interventions. The study aimed to develop a patient-reported experience measure regarding psychological care (PREMIUM-PSY) using adaptive testing and investigate its association with quality of life. In a multicenter study involving 443 patients with SMD, PREMIUM-PSY demonstrated both validity and efficiency (6-item average). Positive patient experiences were associated with enhanced mental and physical quality of life (β = 3.15[2.17;4.12], p < 0.001 and β = 1.18[0.04;2.32], p = 0.042), suggesting PREMIUM-PSY's potential for optimizing psychological care outcomes.
The power of the placebo effect in diabetes: A systematic review and meta-analysis
2023, Primary Care Diabetes
This review aims to identify the magnitude of the placebo effect in people with type 2 diabetes mellitus. Literature research was conducted Medline, Embase and Virtual Health Library for studies published between the date of inception and June 2021. The eligibility criteria included randomized controlled trials, showing comparison to placebo, having participants with type 2 diabetes mellitus, and having glycated hemoglobin (HbA1c) as the primary outcome. Meta-analysis was conducted with the effect of changing HbA1c in relation to the baseline. Exploration of heterogeneity was performed.The meta-analysis showed an increase in the average of HbA1c compared to the baseline of 0.14% (95% CI: 0.07–0.21). There was a significant difference between follow-up times (p = 0.03) and between administration routes (p = 0.01), with an increase in HbA1c in the oral route [0.15% (95% CI: 0.07–0.23)]. The meta-regression of the year of publication showed a significant downward trend (p = 0.01) of the increase in HbA1c compared to the baseline.In this study, the expected placebo effect of Hba1c reduction was not found; instead, higher Hba1c levels were observed in the control groups, although this effect was reduced over the years.
Registration: PROSPERO ID CRD42020172797
The placebo component of pain treatments, towards an optimization of the effectiveness
2023, Actualites Pharmaceutiques
L’effet placebo contribue à l’efficacité de toutes substances actives, il est la part non pharmacologique du traitement. La douleur ayant une forte composante émotionnelle, il est important d’optimiser cet effet et d’éviter son corollaire négatif, l’effet nocebo. Faire un point sur les connaissances et les réflexions actuelles dans ce domaine permet de mettre l’accent sur les conduites adaptées.
The placebo effect contributes to the effectiveness of all active substances; it is the non-pharmacological part of the treatment. Since pain has a strong emotional component, it is important to optimize this effect and avoid its negative corollary, the nocebo effect. Taking stock of current knowledge and thinking in this area allows us to focus on appropriate behaviors.
Knee-extensor strength, symptoms, and need for surgery after two, four, or six exercise sessions/week using a home-based one-exercise program: a randomized dose–response trial of knee-extensor resistance exercise in patients eligible for knee replacement (the QUADX-1 trial)
2022, Osteoarthritis and Cartilage
Citation Excerpt :
The proportion of patients postponing and choosing surgery across the three groups appeared similar – indicating that the decision to postpone surgery was independent of the prescribed exercise therapy dosage (not powered for this outcome). A contributing factor explaining the large number of patients postponing surgery could be the non-specific effect of the applied ‘model’ of coordinated non-surgical and surgical care16,59,60,62–64. In this ‘model’, the patients' decision on surgical treatment was re-evaluated by the patient and orthopedic surgeon after the exercise period.
To investigate firstly the efficacy of three different dosages of one home-based, knee-extensor resistance exercise on knee-extensor strength in patients eligible for knee replacement, and secondly, the influence of exercise on symptoms, physical function and decision on surgery.
One-hundred and forty patients eligible for knee replacement were randomized to three groups: 2, 4 or 6 home-based knee-extensor resistance exercise-sessions per week (group 2, 4 and 6 respectively) for 12 weeks. Primary outcome: isometric knee-extensor strength. Secondary outcomes: Oxford Knee Score, Knee injury and Osteoarthritis Outcome Score, average knee pain last week (0–10 numeric rating scale), 6-min walk test, stair climbing test, exercise adherence and “need for surgery”.
Primary analysis: Intention-to-treat analysis of 140 patients did not find statistically significant differences between the groups from baseline to after 12 weeks of exercise in isometric knee-extensor strength: Group 2 vs 4 (0.003 Nm/kg (0.2%) [95% CI -0.15 to 0.15], P = 0.965) and group 4 vs 6 (−0.04 Nm/kg (−2.7%) [95% CI -0.15 to 0.12], P = 0.628). Secondary analysis: Intention-to-treat analyses showed statistically significant differences between the two and six sessions/week groups in favor of the two sessions/week group for Oxford Knee Score: 4.8 OKS points (15.2%) [1.3 to 8.3], P = 0.008) and avg. knee pain last week (NRS 0–10): −1.3 NRS points (−19.5%) [-2.3 to −0.2], P = 0.018. After the 12-week exercise intervention, data were available for 117 patients (N = 39/group): 38 (32.5%) patients wanted surgery and 79 (67.5%) postponed surgery. This was independent of exercise dosage.
In patients eligible for knee-replacement we found no between-group differences in isometric knee extensor strength after 2, 4 and 6 knee-extensor resistance exercise sessions per week. We saw no indication of an exercise dose–response relationship for isometric knee-extensor strength and only clinically irrelevant within group changes. For some secondary outcome (e.g., KOOS subscales) we found clinically relevant within group changes, which could help explain why only one in three patients decided to have surgery after the simple home-based exercise intervention.
ClinicalTrials.gov identifier: NCT02931058. Preprint: https://doi.org/10.1101/2021.04.07.21254965.

View all citing articles on Scopus

View full text

Chapter Nine - The Role of Patient–Practitioner Relationships in Placebo and Nocebo Phenomena

Abstract

Section snippets

Background

The Patient–Practitioner Interaction: A Sociobiological Approach

Interpersonal Healing

Signs and Meaning

Connecting the Dots: A Clinical Approach

Conclusion

Acknowledgments

Pain

Neuroscience

Neuroscience

The Lancet. Neurology

Biological Psychiatry

European Neuropsychopharmacology

Social Science & Medicine

The Lancet

The Lancet (London, England)

International Review of Neurobiology

Applied and Preventive Psychology

Pain

Pain

NeuroImage

Mayo Clinic Proceedings

Trends in Neurosciences

Conditioned pharmacotherapeutic effects: A preliminary study

Psychosomatic Medicine

The sociophysiology of caring in the doctor-patient relationship

Journal of General Internal Medicine

Toward a biopsychosocial understanding of the patient-physician relationship: An emerging dialogue

Journal of General Internal Medicine

The doctor-patient relationship revisited. An analysis of the placebo effect

Annals of Internal Medicine

Open-label versus double-blind placebo treatment in irritable bowel syndrome: Study protocol for a randomized controlled trial

Trials

The powerful placebo

Journal of the American Medical Association

Placebo effects: Understanding the mechanisms in health and disease

The biochemical and neuroendocrine bases of the hyperalgesic nocebo effect

Journal of Neuroscience

Opioid-mediated placebo responses boost pain endurance and physical performance: Is it doping in sport competitions?

Journal of Neuroscience

The effect of treatment expectation on drug efficacy: Imaging the analgesic benefit of the opioid remifentanil

Science Translational Medicine

Nocebo and pain: An overview of the psychoneurobiological mechanisms

Pain Reports

Analgesic effects of branding in treatment of headaches

British Medical Journal (Clinical Research Ed.)

Placebo response, sustained partnership, and emotional resilience in practice

The Journal of the American Board of Family Practice

Neuroendocrine perspectives on social attachment and love

Psychoneuroendocrinology

Open-label placebo treatment in chronic low back pain: A randomized controlled trial

Pain

Placebo, nocebo, and learning mechanisms

Tell me the truth and i will not be harmed: Informed consents and nocebo effects

The American Journal of Bioethics: AJOB

Placebos and painkillers: Is mind as real as matter?

Nature Reviews. Neuroscience

Nocebo hyperalgesia: How anxiety is turned into pain

Current Opinion in Anaesthesiology

Experimental designs and brain mapping approaches for studying the placebo analgesic effect

Relieving pain using dose-extending placebos

Pain

Understanding placebo and nocebo responses for pain management

Current Pain and Headache Reports