Nocebo Effect

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Original Editor - Melissa Coetsee

Top Contributors - Melissa Coetsee, Vidya Acharya and Kim Jackson  

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.

Factors that contribute

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

Factors that influence the nocebo effect

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
• Over-reliance on medical care
• Increased psychological and physical distress

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 pronociceptive system (cholecystokinin pathway)
• Activation of various cortical and spinal cord mechanisms - Increased anxiety which activates the hypothalamic-pituitary-adrenal axis
• Affects 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.See also: Medical imaging

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.

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.

See also:

• 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 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 - the word degenerative discs may sound non-threatening to a clinician, but scary to a patient

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

Emotive power of words

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.

Especially, reconceptualising pain as a complexly influenced and emergent phenomenon rather than a linear consequence of tissue damage is warranted.

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. 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.

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 to make the art and science of medicine work together, by combining 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.

We can shape our therapist-patient communication, patient treatment expectations, and clinic design and atmosphere, to name a few examples.In each patient encounter, we should strive to discover the patient's expectation and then deliver and exceed it to the extent that it doesn't cause more harm. If a patient's expectation could cause harm (eg, an early magnetic resonance imaging scan the patient doesn't need), the onus is then on each of us to reshape the patient's beliefs to be consistent with best practice.

realistic without being fatalistic.

As clinicians, we need a keen sensitivity to how our patients are responding to the words we use.

In summary, all musculoskeletal conditions must be viewed within a more comprehensive framework that takes account of biomedical issues and includes how patients perceive their injuries, their disabilities, their pain, and how they make sense of what is happening to them. The words we (and our patients) use are crucial to this more comprehensive view. Eccleston and Crombez8 state, “Pain is an ideal habitat for worry to flourish.” Without such a reconceptualization, clinicians will likely remain unaware of the potential harm that their words may hold. As a result, they may continue to unknowingly fertilize pain's vulnerable ground.

COP are well-placed to provide primary health care that reduces requests for imaging, strong analgesic medications, and invasive pain treatments, and to mitigate the commonly-held belief that where there is pain there must be an injury. COP practitioners could do so by triaging, providing patient-focussed communication and supportive relationships, helping to re-engage in physical activity and providing short-term symptom relief, and by increasing their focus on advocacy for patients. To effectively redirect patients’ journeys away from provider-shopping and consecutive disappointments, long-term educational efforts at profession-level need to be paired with public outreach campaigns and the disincentivizing of passive low-value care.

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. 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; focus on language towards hopes, and not hurts; focus on what one can do rather than what can't be done

In Rehabilitation

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) - delayed recovery and dependence which could result in lack of self-efficacy and negative expectations

Examples in the literature

• 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.
• Healthcare advice that emphasises structural/anatomical vulnerability of the spine from radiographic imaging, resulted in patients having greater reported disability.
• Various studies have reported that chronic back pain can in part be iatrogenic due to misconceptions and negative beliefs instilled by practitioners.
• Suggestions or practices that could promote the belief that deterioration is inevitable without continuous intervention/'maintenance' therapy.

Harmful words	Reframed wording
Instability	Needs more strength and control
Chronic	It may persist, but you can overcome it
Bone out of place/ subluxation
Lumbar dysfunction/ disc bulge	Episode of back pain; lumbar sprain
	I recommend we add volitional step training in your program. It has been shown that this type of training can be highly effective in reducing the risk of falls. The use of volitional step training is very beneficial for your training and performance”.
Tear	Pull
Trapped nerve	Tight, but can be stretches/mobilised

In Orthopaedics

Orthopaedic surgeons play 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.

Reframing common orthopaedic words

Harmful Words	Reframed Wording
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"
You have the joint of an 80-year old
Your joint is bone on bone	A lot of people without pain also have this; 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

Ethics

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 expectations and beliefs harboured by the patient, the physician and the relationship that is engendered between the two, all of which come into play during the consent process. However, the very process of describing potential adverse events may lead to intensivists inducing nocebo responses, leading to increased fear, anxiety and subsequently harm, which are in direct conflict with the principles of beneficence and non-maleficenceAn alternative is to reframe the risks of the procedure in a way that reassures the patient and their family, rather than causing anxiety. For example, rather than say that ‘oesophageal perforation is a risk of a tracheostomy insertion’, one could say ‘as damage to nearby tissues such as the oesophagus can occur, we always perform this procedure with the use a special camera in the breathing pipe (a bronchoscope) to make the procedure as safe as possible’. A recent study explored the concept of a ‘layered consent’ process whereby patients chose the amount of information they consumed, with a focus on the different information needs of patients and a preference for understanding benefits over risk.19 Such an approach may not only improve patient agency but potentially reduce the risk of nocebo effects.

Clinicians are obligated to explain the potential adverse events when prescribing medications or recommending procedures. It is well documented that a meticulous description of all potential adverse events during the process of informed consent leads to an increased incidence of adverse effects being reported,6 which creates a dilemma for the physician. By giving the patient reasonable information as part of the informed consent process, allowing them to make personal choices which impact them, there is an unavoidable development of nocebo leading to maleficence, however, elimination of risk information is not an option. This creates an ethical tension for intensivists who seek full disclosure of potential adverse events versus the risk of harm via unintentional nocebo effects. However, as the examples above illustrate, it is possible to combine negative signals of risk with positive ones, such as the steps taken to reduce risk and reframing the context of treatment. The ‘layered consent’ process may also lend itself well to the clinical environment, thus giving patients greater agency. Interestingly, the ‘layered consent’ process is being used in a current multicentre trial, suggesting an alternative to the standard consent process for a clinical trial19. These strategies have the multiple benefits of reducing the nocebo effect while also reassuring and empowering the patient as well as keeping within guidelines of ethical practice.

To this extent, a balance must exist between communicating important clinical information and ensuring that every attempt is made to minimize negative instructions and a negative therapeutic context.

Informed Consent

One of the basic ethical duties in health care is to obtain informed consent from patients before treatment; however, the disclosure of information regarding potential complications or side effects that this involves may precipitate a nocebo effect.

Summary

As with the placebo effect, the nocebo response highlights the powerful interaction between the therapeutic context and the patient's mind-brain interaction

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