Nocebo Effect

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Original Editor - Melissa Coetsee

Top Contributors - Melissa Coetsee, Kim Jackson and Vidya Acharya  

Introduction

The nocebo effect, the opposite of the placebo effect, is the psychobiological phenomenon of adverse treatment effects that cannot be ascribed to specific treatment mechanism, but rather is shaped by expectations and learning.In contrast to the placebo effect of positive expectation which results in health benefits, the nocebo effect worsens the health status due to negative beliefs and expectations. It refers to the adverse outcomes that occur as a result of patient expectations and subconscious learning .

There is an increasing body of evidence demonstrating that the way in which clinicians communicate can be a substantial source of nocebo effects, resulting in adverse symptoms that are far more significant than previously thought.

Contributing Factors

The following factors can contribute to a nocebo effect:

• The healthcare setting
• Patient-practitioner interaction (verbal and non-verbal communication)
• Patient-practitioner characteristics (reputation, previous negative experiences)
• Actions that convey meaning
• Words/language that have negative meaning attached to them
• Social media/pamphlets focusing on disease and biomedical models

Manifestation of Nocebo Effect

• Aggravation of pain, not related to disease/treatment factors
• Treatment 'side-effects'
• Learnt helplessness; loss of self-efficacy and self-esteem
• Fear avoidance
• Pain catastrophising
• Over-reliance on medical care
• Increased psychological and physical distress
• Increase in perceived and actual disability

Physiology

For a long time, the placebo and nocebo effects were largely explained by psychological mechanisms, but research has revealed that biological factors are involved. Some of the physiological mechanisms which are activated by negative expectancy include:

• Activation of the pro-nociceptive system (cholecystokinin pathway)
• Activation of various cortical and spinal cord mechanisms - Increased anxiety which activates the hypothalamic-pituitary-adrenal axis
• Effect on neural pathways that mediate pain experience

For more on pain modulation follow the links to these pages: Pain facilitation and inhibition; Pain-modulation; Pain descending pathways

Evidence of the Nocebo Effect

A meta-analysis has demonstrated that the effect sizes related to verbally induced nocebo can be significant - negative verbal information can even convert non-nociceptive stimulation into an experience of pain.

Below are some specific conditions/settings that have been researched:

• ICU: Negative 'warnings' prior to procedures (such as inserting lines) can result in hyperalgesia and distress. Family meetings also require a careful consideration of language used.
• Performance: The nocebo effect can negatively influence muscle force production, endurance and response accuracy.
• Postural Stability: Negative performance expectations (evoked by instructions) can negatively impact objective (increased postural sway) and subjective postural stability.
• Low back pain (LBP): Routine imaging leads to worse outcomes compared to a clinical report (reassurance of incidental findings). Early MRI's for LBP results in longer duration of disability, higher medical cost and worse outcomes regardless of radiculopathy (after controlling for severity and demographics).
• Hyperalgesia: Higher levels of fear of pain significantly increases stress levels and is associated with increased nocebo hyperalgesia.
• Medical Imaging: The use of negative words to describe a non-threatening situation, for example, diagnostic descriptions of imaging reports - can be perceived by patients as implying an increased severity of their condition, which can lead to poor outcomes.Healthcare advice that emphasises structural/anatomical vulnerability of the spine from radiographic imaging, resulted in patients having greater reported disability. See also: Medical imaging
• A study found that when patients with low back pain are told that a leg flexion test could lead to pain, reported an increase in pain and performed fewer repetitions, than those who were told the test is painless.
• Various studies have reported that chronic back pain can in part be iatrogenic due to misconceptions and negative beliefs instilled by practitioners.

Language Matters

Healthcare is infiltrated with meaning and words, from the jargon of medical terms to the waiting room, interview, relaying of information and clinical mannerisms - which can all influence outcomes. Both the way we communicate and the words we use can be harmful.

Good communication

Communication

Research has shown that good communication forms an integral part of efficient and quality health care. The way medical information is delivered (non-verbal and verbal factors) by clinicians can have a significant impact on patient outcomes.Clinicians should mindful of tone, affect, facial expressions and word choice.

For more detail, visit the following pages:

• Communication: the most potent tool in the box
• Communication to improve health outcomes

Words

Like medication, words can change the way a person thinks and feels:

• Words have emotive power and can generate good or bad emotions
• Words can prompt actions that can lead to negative or positive behaviour change
• The meaning attached to words are influenced by one's background and culture - for example, the word degenerative discs may sound non-threatening to a clinician, but scary to a patient
• Words affect patients' response to medical interventions

"Words are, of course, the most powerful drug used by mankind" - Rudyard Kipling

Pathoanatomical language still dominates the health care sector, with less acknowledgement of the well researched psychological factors involved in pain and disability. An improved understanding of pain as a phenomenon that is mediated by the mind may help to increase awareness of the meaning behind the words we choose.

Watch this video on the power of words:

Clinical Implications

It is important to be aware of the impact that words (when we educate, interview, assess) can have on patient expectations, and subsequently on health outcomes.

“Pain is an ideal habitat for worry to flourish”; Without awareness of the potential harm that words can do, clinicians may continue to unknowingly fertilize pain's vulnerable ground.

Clinicians who have short interactions with patients, need to carefully consider what to say and convey in the limited time, and those who have prolonged contact with patients (such as allied health practitioners) should continually focus on positive reframing and challenge negative beliefs.

Reframing Words

There is no one formula for how we might use language within clinical practice. Not all medicalized language is harmful to all individuals. Below are some guiding principles that can help to minimise nocebo effects:

• Positive framing: Rephrasing medical information and descriptions to focus on the positive elements, without being dishonest. Realistic but not fatalistic. This usually includes words of encouragement and positive words. Minimise the attention placed on negative aspects.
• Patient engagement: Involve the patient in the knowledge process to determine what they want to know and explore patient expectations and beliefs
• Positivity: Focus on factors that eliminate worry and fear and focus on language towards hopes, and not hurts, on what one can do rather than what can't be done

Here are some examples of word reframing:

Potentially harmful words	Reframed wording
Instability	Needs more strength and control
Chronic	It may persist, but you can overcome it
Bone out of place	Normal individual variation
Lumbar dysfunction/ disc bulge	Episode of back pain; lumbar sprain
If we do not work on your balance you will definitely fall again	Balance training can be highly effective in reducing the risk of falls
Tear	Pull; defect
Trapped nerve	Tight, but can be stretches/mobilised
Frozen/ locked	Tight; stiff
Wear and tear (may imply the need for a technical fix); Degenerative changes	Normal age changes; A lot of people without pain also have this
You have to do X before "..." "...your insurance will cover imaging" "...you can get more medication"	If you do X, you can "..." "...avoid surgery" "...prevent worsening" "...rely on less medication"
Your joint is bone on bone	Narrowing/tightness
That is the worst joint I have ever seen	The good news is, we can help
No wonder you are in pain	This doesn't have to be a life sentence to pain
You are going to have to live with this	You may need to make some adjustments
Bulge/herniation	Bump, swelling
This is going to "sting/burn"	I am about to inject an anaesthetic that numbs the skin

Role of the Multi-disciplinary Team

Rehabilitation Professionals	Medical Doctors/ Specialists
Rehab professionals are well-placed to provide primary health care that reduces requests for imaging, and to mitigate the commonly-held belief that where there is pain there must be an injury. It is important to provide patient-focused communication and build supportive relationships.	Doctors plan an important role in conveying image findings and information regarding treatment options and prognosis. Single and at times offhand statements can heavily influence recovery expectations. The inappropriate use of routine medical imaging can also be harmful, especially when the results are not conveyed in context and with sensitivity.

Rehabilitation professionals need to be aware of the following actions and their possible negative effects on patient outcomes:

• Using unhelpful diagnostic labels: Can promote fear of movement and catastrophising, and can create negative expectancy
• Failure to focus on positive aspects of structures in the human body: Can lead to false perceptions of vulnerability and lead to fear-avoidance
• Excessive attention to tissue modification induced through treatment: Reinforces dependence, discourages self-management and promotes beliefs in purely biological causes of pain
• Over-emphasis on teaching 'proper' postures: Triggers fear and limits contextual adaptation
• Overuse of low-value-based therapies (such as electrotherapy) instead of therapies with more robust evidence: Delayed recovery and dependence which could result in lack of self-efficacy and negative expectations
• Advocating maintenance therapy: including any suggestions or practices that could promote the belief that deterioration is inevitable without continuous intervention/'maintenance' therapy

Ethical Considerations

• Informed Consent:' Evidence has shown that information disclosure about potential side effects of treatment, may create expectancies which contribute to adverse effects and may hinder the positive effects of the treatment.The very process of describing potential adverse events can therefore lead to nocebo responses (i.e. harm). It is therefore necessary to reframe the risks of interventions in a wat that reassures (eg. "as X can occur, we always do Y to make sure it is as safe as possible). The risk of harm through a nocebo effect needs to be balanced with the obligation of full disclosure. 'Layered consentis one way of achieving this.
• First do no harm: This ethical principle emphasises why it is important for all clinicians to be aware of the possible harm that can be done through their words. If a patient's expectation/request could cause harm (eg. an early MRI that is not indicated or insisting on only passive treatment modalities), it is necessary to reshape the patient's beliefs to be consistent with best practice
• Truth-telling: It is not ethical to use positive words, which are in fact false (eg. telling a patient they will definitely recover fully, when this is not the case). One can however leverage the positive effects of words and combine evidence based interventions with a positive therapeutic experience.At the same time, the effect of evidence-based interventions are at risk of being minimised when combined with a negative therapeutic experience. It is important to balance communicating important clinical information and ensuring that every attempt is made to minimize negative expectancies.

Summary

As with the placebo effect, the nocebo response highlights the powerful interaction between the therapeutic context and the patient's mind-brain interaction.All healthcare professionals need to be aware of the potential harm that can be done through verbal and non-verbal communication and should seek to improve their communication skills through word reframing, patient-centred care and a supportive therapeutic relationship.