What Happens When a Sugar Pill Turns Sour?
How the nocebo effect is tacking itself onto to the list of side-effects associated with countless medical treatments.
Just as Anakin Skywalker revealed his dark side when he shifted into the galactically feared super-villain Darth Vader, the well-known and well-regarded placebo possesses a rather dark side as well.
Throughout the past decade, society has become increasingly familiar with the concept of a placebo and its common mode delivery as a sugar pill that can provide patients with relief from a number of negative symptoms they may be experiencing. The healing powers associated with this sugar pill have been linked to an individual’s expectations surrounding a positive reward. These learned preconceptions we process surrounding the delivery of a medical treatment can quickly become somewhat of a double-edged sword when this perspective begins to morph into an expectation or fear that something bad is going to happen following the delivery of a medication or treatment. This phenomenon is known as the nocebo effect, or more casually, the placebo’s evil twin.
The nocebo effect has been formally defined as a harmless substance or treatment that when taken by a patient elicits negative side effects or symptoms due to the patient having expectations surrounding its results. Although the concept of a sugar pill causing sour side effects may seem rather far-fetched, a significant number of scientific studies have provided a wealth of supporting evidence indicating the legitimacy of the nocebo effect.
Like a Jedi using the force to control the mind of another, the nocebo will often use the words of a physician or care-provider to provide it with its mild altering abilities. It has long been thought that the best way to properly prepare a patient for experiencing pain is by using terms such as “this might hurt quite a bit” or “brace yourself for a pinch”, however, studies have recently revealed that these well-intended words are inflicting a form of pain on their own regardless of if a medical treatment is present or not. One experiment in particular analyzed a patient’s perception of pain after being injected with a radiographic substance by determining how their sensation varied depending on the phrases the doctor used prior to delivering the injection. They found that the more frequently the doctor used words such as “sting”, “burn”, or “hurt”, the greater the degree of discomfort was felt by the patient.
In 2012, researchers from the Technical University of Munich produced an in-depth review of 31 empirical studies that focused on the clinical applications of a nocebo. Follow this review, they concluded that not only does the nocebo effect exist, but it has been silently leaching its way into doctors’ offices and pharmacies around the world for years.
The researchers conducting this review set out on a mission to portray an accurate representation of the neurobiological mechanisms that influence the strength of a nocebo. They questioned its relatedness to the more widely studied placebo effect, and if the nocebo is caused by the same type of learning and conditioning as what has been deemed to be the source of the placebo.
A number of these studies provided direct evidence that the nocebo effect can elicit a physical response in a patient’s perception of pain. Like the placebo effect, a few central chemical messengers, including dopamine and endogenous opiates, have been linked to the intensity of the experienced nocebo effect. Where the brain of the patient delivered a placebo will display an increased level of these neurotransmitters, a patient’s brain following the delivery of a nocebo will exhibit a sharp decrease in the internal levels of these same chemicals. This is an extremely logical finding as a release of dopamine in the brain is normally associated with a decrease in anxiety and pain levels, both of which are elevated when a patient is delivered a negative nocebo treatment.
One experimental study put the nocebo effect to the test by randomly dividing 50 individuals with chronic back pain into two groups prior to a preforming repetitive leg flexions. One group was told that the test would cause a slight increase in pain whereas the other group was told there would be no increase in pain. The group provided with the negative information reported a significantly higher level of pain than those given the neutral information and preformed fewer leg flexions as a result. This showed researchers that the physicians’ words alone had enough power to cause a physiological response in the patient’s response.
Similar to how a Jedi uses the Force to control the mind of their target, the nocebo will often use the words of a doctor or a care provider as its main source of power. It has long been thought that that proper way to prepare a patient for experiencing any pain, the care provider must describe a treatment using phrases such as “this might hurt quite a bit” in order to invoke anxiety so they know what to expect. One study in particular showed that these well-intended words of a doctors are actually inflicting a form of pain on their own even regardless of if a medical treatment is present or not. This experiment analyzed a patient’s perception of pain after being injected with a radiographic substance and how their level of discomfort varyied depending on the phrases that doctor used before delivering the injection. They found that the more frequently words such as “sting”, “burn”, or “hurt” were used, the greater the degree of discomfort the patient felt. However, if a care-provider neglects to disclose the slew of side-effects accompanying a given treatment, they may be at risk of being accused of malpractice or in the most extreme cases, getting sued for mistreatment.
The moral obligation surrounding a physician’s duty to inform their patients of any adverse effects that may be associated with a given medication, chemotherapy, or psychological treatment causes them to walk a fine line in order to avoid adding ‘bad-vibes’ to the list of negative side effects of a treatment. If a patient believes that they will experience harm because of a prescribed treatment, they may transform this notion into a self-fulfilling prophecy. Alternatively, some individuals may talk themselves out of taking their medication following an overly detailed review of the ill effects associated with it. This put physicians in a tough spot in terms of deciding how they will deliver a pre-treatment script to a patient without making a rather symptom laden bed for their patient to rest in.
Thankfully, this review also provided several tips and tricks for physicians attempting to avoid the nocebo effect, one of which emphasizes the importance placing any potential side effects under a more tolerable light. Using this strategy, a physician will attempt to phrase any possible adverse effects more positively by stating “most patients tolerate this treatment very well”, instead of “5% of patients report…”. The effectiveness of this tactic was highlighted in a study on the importance of briefing a patient prior to the delivery of an influenza vaccine. If the care-provider isn’t as keen to perform the literary work of Shakespeare on a side-effects list, they can instead directly ask the patient if they would like to hear the information regarding the mild side effects of a treatment or not. Although the patient must still be informed of any serious implications associated with this treatment, filtering out the overwhelming “what if’s” and “maybes” can steer them away from entering a spiral of anxious thoughts regarding the treatment they are about to receive.
Figure 1: A patient’s reported pain level after being administered an influenza vaccine based on the words and phrases used by the physician prior to its delivery.
Figuring out how to communicate effectively to handle a patient’s fears and anxieties surrounding a medical treatment appears to be almost as challenging for physicians as fighting the illness itself. Ironically, the best weapon for a physician to bring to a battle against a nocebo is their words, or in some cases with the permission of the patient, the lack thereof. This review, along with several additional studies centred around the mind controlling power of the nocebo, emphasize the harsh reality of the phrase “the less you know the better” and that sometimes being left in the dark may be more beneficial than you may think.
Reference Article
Häuser, W., Hansen, E., & Enck, P. (2012). Nocebo Phenomena in Medicine. Deutsches Ärzteblatt International. https://doi.org/10.3238/arztebl.2012.0459
For more information on the Nocebo effect check out these links:
https://www.smithsonianmag.com/science-nature/what-is-the-nocebo-effect-5451823/
https://www.webmd.com/balance/features/is-the-nocebo-effect-hurting-your-health
Until next time,
-Kalli










