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Understand the barriers and bottlenecks which limit desired behaviors of patients and HCPs in the pharmaceutical industry and how messaging boosted by heuristic science can effectively influence any stakeholder audience.

Nocebo Effect

Nocebo Effect: When sugar pills make things worse

18 FEB, 2021

A lot is known about the placebo effect - when sham treatments such as sugar pills induce a positive change in patients or reduce a medical problem’s intensity. The placebo effect is a non-specific part of a treatment where psychological factors like expectations and past experiences trigger a positive change. However, much lesser is known about the placebo’s counterpart called the Nocebo Effect. The nocebo effect refers to a negative change or worsening of symptoms induced by a placebo or an active treatment. For example, a sugar pill prescription for a headache may worsen the headache or induce body ache. The nocebo effect can turn into a costly burden for doctors, patients, and insurers. Notably, lowered trust between doctors & patients and the economic burden of multiple consultations.

In one study, researchers gave college students a fake radio-frequency stimulus and told them that a current would pass through their heads. Over 66% of the students experienced a mild headache even though nothing was passing through their heads. In another study, researchers concluded that the nocebo effect was responsible for abdominal symptoms in those with a negative lactose intolerance test.

One ethical treatment practice is to ask for informed consent where a doctor impartially states the risks and expected outcomes of a particular treatment. Informed consent includes attempts to ensure a patient understands the risks and complications. Mounting evidence suggests that the very act of explaining risks and possible negative side effects acts like a verbal suggestion that increases the likelihood of negative outcomes. Experimental evidence indicates that such discussions induce anticipatory anxiety about side effects like pain. And that starts a cascade of physiological processes like activating cholecystokinin that facilitates pain transmission.

Research suggests that the most common nocebo effects are pain, drowsiness, nausea, headache, poor concentration, and fatigue. Sometimes, nocebo symptoms go hand-in-hand with iatrogenic symptoms (unexpected symptoms caused by the diagnostic test or treatment procedure), such as rashes caused by medical tools.

Researchers suspect that the nocebo effect has both psychological and physiological components. The psychological component includes 3 factors:

  • Patients’ expectations & beliefs: Expecting negative outcomes from a treatment due to past experiences, fears, or even pessimism can induce the nocebo effect.
  • Nature of communication between doctors and patients: Non-verbal cues such as body language or vocal tone can suggest bad expectations, complications, or ambiguity. The choice of words can seed a pre-occupation with adverse outcomes.
  • Extra attention to negative information: Informed consent and detailed discussions focusing on symptoms like pain, anxiety, discomfort, etc., bring the negative symptoms into awareness and cause them to manifest through higher expectations.

In short, a patient’s perception affects the treatment outcome in a non-trivial way. The confirmation bias can overestimate the severity or frequency of side-effects. A thinking error called misattribution of cause can make a patient misinterpret if a side-effect is caused by the treatment or is a part of an unforeseen complication from another medical condition or life stressor.

To minimize the nocebo effect, researchers suggest 4 solutions:
  • Positive framing: Using positive words that suggest gains or improvements instead of negative words that suggest avoiding negative outcomes.
  • Contextualized informed consent: Primarily focusing on practical expectations and limited but sufficient information on risks and negative outcomes without overindulging them.
  • Non-information: Patients get to select what categories of negative information need discussions. A patient can autonomously decline to hear about rare or trivial side effects, but a doctor still briefs the patient on irreversible and significant side effects.
  • Explain the theory and test: Doctors can create the narrative of explaining the theory involved in the medical problem and testing it out with well-tested treatments to avoid ambiguous interpretations.
  1. Colloca, L., & Miller, F. (2011). The Nocebo Effect and Its Relevance for Clinical Practice. Psychosomatic Medicine, 73(7), 598-603.
  2. Schweiger, A., & Parducci, A. (1981). Nocebo: the psychologic induction of pain. The Pavlovian journal of biological science, 16(3), 140–143.
  3. Vernia, P., Di Camillo, M., Foglietta, T., Avallone, V., & De Carolis, A. (2010). Diagnosis of lactose intolerance and the “nocebo” effect: The role of negative expectations. Digestive And Liver Disease, 42(9), 616-619.
  4. Wells, R., & Kaptchuk, T. (2012). To Tell the Truth, the Whole Truth, May Do Patients Harm: The Problem of the Nocebo Effect for Informed Consent. The American Journal Of Bioethics, 12(3), 22-29.
  5. Benedetti, F., Lanotte, M., Lopiano, L., & Colloca, L. (2007). When words are painful: Unraveling the mechanisms of the nocebo effect. Neuroscience, 147(2), 260-271.
  6. Bootzin, R., & Bailey, E. (2005). Understanding placebo, nocebo, and iatrogenic treatment effects. Journal Of Clinical Psychology, 61(7), 871-880.
  7. Planès, S., Villier, C., & Mallaret, M. (2016). The nocebo effect of drugs. Pharmacology Research & Perspectives, 4(2).